المؤلفون: Jamieson A; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, The University of British Columbia and BC Cancer, Vancouver, British Columbia, Canada amy.jamieson@vch.ca., Grube M; Department of Women's Health, Tübingen University Hospital, Tübingen, Germany., Leung S; Department of Molecular Oncology, University of British Columbia, Vancouver, British Columbia, Canada., Chiu D; Department of Molecular Oncology, University of British Columbia, Vancouver, British Columbia, Canada., Lum A; Department of Molecular Oncology, University of British Columbia, Vancouver, British Columbia, Canada., Kwon JS; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, The University of British Columbia and BC Cancer, Vancouver, British Columbia, Canada., Talhouk A; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, The University of British Columbia and BC Cancer, Vancouver, British Columbia, Canada., Gilks B; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Kommoss S; Department of Women's Health, Tübingen University Hospital, Tübingen, Germany., McAlpine JN; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, The University of British Columbia and BC Cancer, Vancouver, British Columbia, Canada.

المصدر: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society [Int J Gynecol Cancer] 2024 Apr 01; Vol. 34 (4), pp. 544-549. Date of Electronic Publication: 2024 Apr 01.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: BMJ Country of Publication: England NLM ID: 9111626 Publication Model: Electronic Cited Medium: Internet ISSN: 1525-1438 (Electronic) Linking ISSN: 1048891X NLM ISO Abbreviation: Int J Gynecol Cancer Subsets: MEDLINE

مواضيع طبية MeSH: Neoplasm Recurrence, Local*/epidemiology , Neoplasm Recurrence, Local*/pathology , Endometrial Neoplasms*/pathology, Female ; Humans ; Retrospective Studies ; Neoplasm Staging ; Radiotherapy, Adjuvant

مستخلص: Objectives: Optimal management of patients with stage IA p53abn endometrial cancer without myoinvasion, classified as intermediate risk in the 2020 European Society of Gynaecological Oncology, European Society for Radiotherapy and Oncology, and European Society of Pathology (ESGO-ESTRO-ESP) guidelines, and the 2022 European Society of Medical Oncology (ESMO) guidelines, is currently unclear. Practice varies from surgery alone to adjuvant radiation±chemotherapy. Our aim was to assess the risk of disease recurrence in patients with stage IA p53abn endometrial cancer without myoinvasion compared with stage IA with myoinvasion (<50%).
Methods: Stage IA p53abn endometrial cancers were identified from retrospective cohorts. Cases were segregated into stage IA with no myoinvasion, including (1) tumor restricted to a polyp, (2) residual endometrial tumor, and (3) no residual tumor in hysterectomy specimen, versus stage IA p53abn with myoinvasion (<50%), with treatment and outcomes assessed.
Results: There were 65 stage IA p53abn endometrial cancers with no myoinvasion (22 polyp confined, 38 residual endometrial tumor, 2 no residual in hysterectomy specimen, 3 not specified) and 97 with myoinvasion. There was no difference in survival outcomes in patients with stage IA without myoinvasion (16% of patients recurred, 19% if there was residual endometrial disease) compared with stage IA with myoinvasion (17%). The risk of recurrence was lowest in patients with stage IA p53abn endometrial cancer without myoinvasion treated with chemotherapy±radiation (8%). Most recurrences in patients with stage IA without myoinvasion were distant (89%), with no isolated vaginal vault recurrences, and all except one distant recurrence occurred in patients who had not received adjuvant chemotherapy.
Conclusion: The recurrence rate in patients with stage IA p53abn endometrial cancer without myoinvasion was 16%, highest in the setting of residual endometrial disease (19%), and exceeding the threshold where adjuvant therapy is often considered. The high frequency of distant recurrences observed may support chemotherapy as part of the treatment regimen.
Competing Interests: Competing interests: None declared.
(© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

المؤلفون: McCluggage WG; Department of Pathology, HCS Belfast Health and Social Care Trust, Belfast, UK glenn.mccluggage@belfasttrust.hscni.net., Bosse T; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands., Gilks CB; Department of Pathology, The University of British Columbia, Vancouver, British Columbia, Canada., Howitt BE; Department of Pathology, Stanford University School of Medicine, Stanford, California, USA., McAlpine JN; Gynecology and Obstetrics; Division Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada., Nucci MR; Women's and Perinatal Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA., Rabban JT; Pathology, UCSF, San Francisco, California, USA., Singh N; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Talia KL; Pathology, Royal Women's Hospital and Royal Children's Hospital, Melbourne, Victoria, Australia., Parra-Herran C; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

المصدر: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society [Int J Gynecol Cancer] 2023 Nov 07. Date of Electronic Publication: 2023 Nov 07.

نوع المنشور: Journal Article; Review

بيانات الدورية: Publisher: BMJ Country of Publication: England NLM ID: 9111626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-1438 (Electronic) Linking ISSN: 1048891X NLM ISO Abbreviation: Int J Gynecol Cancer Subsets: MEDLINE

مستخلص: An updated International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma was introduced in June 2023. The new system represents a significant departure from traditional endometrial and other gynecological carcinoma staging systems which are agnostic of parameters such as tumor type, tumor grade, lymphovascular space invasion, and molecular alterations. The updated system, which incorporates all of these 'non-anatomical' parameters, is an attempt to make staging more personalized and relevant to patient prognostication and management, and to align with the European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) risk stratification. Herein, we present a critical review of the new staging system and discuss its advantages and disadvantages. The authors propose that the new FIGO staging system should be first appraised at a multi-institutional and global level with the input of all relevant societies (gynecology, pathology, gynecologic oncology, medical oncology, radiation oncology) to understand the impact, scope, and supporting evidence of the proposed changes. Such a process is fundamental to produce a robust system that pathologists and treating clinicians can adopt.
Competing Interests: Competing interests: None declared.
(© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

المؤلفون: Thompson EF; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, British Columbia, Canada., Shum K; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, British Columbia, Canada., Wong RWC; Department of Pathology, United Christian Hospital, Hong Kong, Hong Kong., Trevisan G; Department of Pathology, Barts Health NHS Trust, London, London, UK., Senz J; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, British Columbia, Canada., Huvila J; Department of Pathology, University of Turku, Turku, Finland., Leung S; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, British Columbia, Canada., Huntsman DG; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, British Columbia, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada., Gilks CB; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada., McAlpine JN; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada., Hoang L; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada., Jamieson A; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada amy.jamieson@vch.ca.

المصدر: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society [Int J Gynecol Cancer] 2022 Sep 13. Date of Electronic Publication: 2022 Sep 13.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: BMJ Country of Publication: England NLM ID: 9111626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-1438 (Electronic) Linking ISSN: 1048891X NLM ISO Abbreviation: Int J Gynecol Cancer Subsets: MEDLINE

مستخلص: Objective: Vulvar squamous cell carcinoma and in situ lesions can be stratified by human papillomavirus (HPV) and TP53 status into prognostic risk groups using p16 and p53 immunohistochemistry. We assessed the significance of vulvar squamous cell carcinoma resection margin positivity for either differentiated vulvar intra-epithelial neoplasia (dVIN) or abnormal p53 immunohistochemistry, and other pathologic variables, in a cohort of patients with HPV-independent (HPV-I) p53 abnormal (p53abn) vulvar squamous cell carcinomas.
Methods: Patients with stage I-II HPV-I p53abn vulvar squamous cell carcinoma with negative invasive margins who did not receive adjuvant radiation from a single institution were included. Tumors underwent margin reassessment using p53 immunohistochemistry. Cases were segregated into (1) morphologic dVIN at margin; or (2) abnormal p53 immunohistochemistry staining at margin without morphologic dVIN (p53abn immunohistochemistry); or (3) margins negative by morphology and p53 immunohistochemistry. Clinicopathologic/outcome data were collected.
Results: A total of 51 patients were evaluated: (1) 12 with dVIN on margin; (2) 12 with p53abn immunohistochemistry on margin without morphologic dVIN; and (3) 27 with margins negative for morphologic dVIN and p53abn immunohistochemistry. The recurrence rate for patients with dVIN or p53abn immunohistochemistry on the margin was equally high at 75% each, compared with 33% with margins negative for morphologic dVIN and p53abn immunohistochemistry (p=0.009). On multivariate analysis, positive in situ margins maintained an association with disease recurrence (p=0.03) whereas invasive margin distance (radial and deep), lymphovascular invasion, and tumor size did not.
Conclusions: Patients with stage I-II HPV-I vulvar squamous cell carcinoma with margins positive for either dVIN or p53abn immunohistochemistry without morphologic dVIN showed increased disease recurrence, regardless of invasive margin distance. These findings show that p53 immunohistochemistry is a useful adjunct for evaluating margin status in HPV-I vulvar squamous cell carcinoma and may support repeat excision for positive in situ margins (dVIN or p53abn immunohistochemistry).
Competing Interests: Competing interests: None declared.
(© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

المؤلفون: Thompson EF; Department of Molecular Oncology, BC Cancer Research Center, Vancouver, British Columbia, Canada., Hoang L; Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia, Canada., Höhn AK; Division of Gynecologic Pathology, University of Leipzig, Leipzig, Germany., Palicelli A; Pathology Unit, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy., Talia KL; Royal Women's Hospital and VCS Foundation, Melbourne, Victoria, Australia., Tchrakian N; Department of Molecular Oncology, BC Cancer Research Center, Vancouver, British Columbia, Canada.; Barts Health NHS Trust, London, UK., Senz J; Department of Molecular Oncology, British Columbia Cancer Research Center, Vancouver, British Columbia, Canada., Rusike R; Barts Health NHS Trust, London, London, UK., Jordan S; Barts Health NHS Trust, London, London, UK., Jamieson A; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, The University of British Columbia, Vancouver, British Columbia, Canada., Huvila J; Department of Pathology, University of Turku, Turku, Finland., McAlpine JN; Gynecology and Obstetrics, Division Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada., Gilks CB; Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia, Canada blake.gilks@vch.ca., Höckel M; Leipzig School of Radical Pelvis Surgery, Division of Gynecologic Oncology, University Hospital Leipzig, Leipzig, Germany., Singh N; Cellular Pathology, Barts Health and NHS Trust and Queen Mary University, London, UK., Horn LC; Division of Gynecologic Pathology, University of Leipzig, Leipzig, Germany.

المصدر: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society [Int J Gynecol Cancer] 2022 Aug 01; Vol. 32 (8), pp. 977-985. Date of Electronic Publication: 2022 Aug 01.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: BMJ Country of Publication: England NLM ID: 9111626 Publication Model: Electronic Cited Medium: Internet ISSN: 1525-1438 (Electronic) Linking ISSN: 1048891X NLM ISO Abbreviation: Int J Gynecol Cancer Subsets: MEDLINE

مواضيع طبية MeSH: Alphapapillomavirus* , Carcinoma, Squamous Cell*/metabolism , Papillomavirus Infections* , Vulvar Neoplasms*/pathology, Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Female ; Humans ; Papillomaviridae/genetics ; Prognosis ; Reproducibility of Results ; Retrospective Studies ; Tumor Suppressor Protein p53/metabolism

مستخلص: Objectives: Vulvar squamous cell carcinoma is subclassified into three prognostically relevant groups: (i) human papillomavirus (HPV) associated, (ii) HPV independent p53 abnormal (mutant pattern), and (iii) HPV independent p53 wild type. Immunohistochemistry for p16 and p53 serve as surrogates for HPV viral integration and TP53 mutational status. We assessed the reproducibility of the subclassification based on p16 and p53 immunohistochemistry and evaluated the prognostic significance of vulvar squamous cell carcinoma molecular subgroups in a patient cohort treated by vulvar field resection surgery.
Methods: In this retrospective cohort study, 68 cases treated by vulvar field resection were identified from the Leipzig School of Radical Pelvic Surgery. Immunohistochemistry for p16 and p53 was performed at three different institutions and evaluated independently by seven pathologists and two trainees. Tumors were classified into one of four groups: HPV associated, HPV independent p53 wild type, HPV independent p53 abnormal, and indeterminate. Selected cases were further interrogated by (HPV RNA in situ hybridization, TP53 sequencing).
Results: Final subclassification yielded 22 (32.4%) HPV associated, 41 (60.3%) HPV independent p53 abnormal, and 5 (7.3%) HPV independent p53 wild type tumors. Interobserver agreement (overall Fleiss' kappa statistic) for the four category classification was 0.74. No statistically significant differences in clinical outcomes between HPV associated and HPV independent vulvar squamous cell carcinoma were observed.
Conclusion: Interobserver reproducibility of vulvar squamous cell carcinoma subclassification based on p16 and p53 immunohistochemistry may support routine use in clinical practice. Vulvar field resection surgery showed no significant difference in clinical outcomes when stratified based on HPV status.
Competing Interests: Competing interests: None declared.
(© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

المؤلفون: Jamieson A; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, The University of British Columbia, Vancouver, British Columbia, Canada., Thompson EF; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada., Huvila J; Department of Pathology, University of Turku, Turku, Finland., Gilks CB; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada., McAlpine JN; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, The University of British Columbia, Vancouver, British Columbia, Canada jessica.mcalpine@vch.ca.

المصدر: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society [Int J Gynecol Cancer] 2021 Jun; Vol. 31 (6), pp. 907-913. Date of Electronic Publication: 2021 Feb 15.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Review

بيانات الدورية: Publisher: BMJ Country of Publication: England NLM ID: 9111626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-1438 (Electronic) Linking ISSN: 1048891X NLM ISO Abbreviation: Int J Gynecol Cancer Subsets: MEDLINE

مواضيع طبية MeSH: Endometrial Neoplasms/*classification , Tumor Suppressor Protein p53/*genetics, Female ; Humans

مستخلص: Over the past decade, our understanding of endometrial cancer has changed dramatically from the two-tiered clinicopathologic classification system of type I and type II endometrial cancer through to the four distinct molecular subtypes identified by The Cancer Genome Atlas (TCGA) in 2013. In both systems there is a small subset of endometrial cancers (serous histotype/high numbers of somatic copy number abnormalities) that account for a disproportionately high percentage of endometrial cancer related deaths. This subset can be identified in routine clinical practice by first identifying the approximately one-third of endometrial cancers that are either ultramutated/ POLE mut tumors, with pathogenic mutations in the exonuclease domain of POLE , or hypermutated/MMRd tumors, with loss of DNA mismatch repair. Immunostaining for p53 stratifies the remaining endometrial cancers into those with wild-type staining pattern and those with mutant pattern staining (p53abn endometrial cancer). This latter group of p53abn endometrial cancer is the subject of this review. Most p53abn endometrial cancers are serous type and high grade, but it also includes other histotypes and lower grade tumors, and has consistently been associated with the poorest clinical outcomes. Although it only accounts for 15% of all endometrial cancer cases, it is responsible for 50-70% of endometrial cancer mortality. A better understanding of the molecular alterations in the p53abn subgroup, beyond the ubiquitous and definitional TP53 mutations, is required so we can identify better treatments for these most aggressive endometrial cancers. Recent evidence has shown improved survival outcomes with the addition of chemotherapy compared with radiation alone in p53abn endometrial cancers. Opportunities for targeted therapy for p53abn endometrial cancers also exist with a proportion of p53abn endometrial cancers known to have homologous recombination deficiency (HRD) or human epidermal growth factor 2 (HER2) overexpression/amplification. This review will provide an overview of our current understanding of p53abn endometrial cancer.
Competing Interests: Competing interests: None declared.
(© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

المؤلفون: Baxter E; Queensland Centre for Gynaecological Cancer Research, The University of Queensland, Brisbane, Queensland, Australia e.baxter@uq.edu.au., Brennan DJ; Department of Gynaecological Oncology, UCD School of Medicine, Mater Misericordiae University Hospital, Dublin, Ireland.; Systems Biology Ireland, University College Dublin, Dublin, Ireland., McAlpine JN; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, The University of British Columbia, Vancouver, British Columbia, Canada.; BC Cancer Agency, Vancouver, British Columbia, Canada., Mueller JJ; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Obstetrics & Gynecology, Weill Cornell Medical College, New York, New York, USA., Amant F; Department of Oncology, KU Leuven, Leuven, Flanders, Belgium.; Centre for Gynaecologic Oncology Amsterdam, Antoni van Leeuwenhoek Netherlands Cancer Institute and Amsterdam University Medical Centres, Amsterdam, Noord-Holland, The Netherlands., van Gent MDJM; Centre for Gynaecologic Oncology Amsterdam, Antoni van Leeuwenhoek Netherlands Cancer Institute and Amsterdam University Medical Centres, Amsterdam, Noord-Holland, The Netherlands., Huntsman DG; BC Cancer Agency, Vancouver, British Columbia, Canada.; Departments of Pathology and Laboratory Medicine and Gynecology and Obstetrics, The University of British Columbia, Vancouver, British Columbia, Canada., Coleman RL; Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Westin SN; Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Yates MS; Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Krakstad C; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Vestland, Norway.; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Vestland, Norway., Quinn MA; Royal Women's Hospital, Melbourne, Victoria, Australia., Janda M; Centre for Health Services Research, The University of Queensland, Brisbane, Queensland, Australia., Obermair A; Queensland Centre for Gynaecological Cancer Research, The University of Queensland, Brisbane, Queensland, Australia.

المصدر: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society [Int J Gynecol Cancer] 2020 Nov; Vol. 30 (11), pp. 1811-1823. Date of Electronic Publication: 2020 May 06.

نوع المنشور: Journal Article; Review

بيانات الدورية: Publisher: BMJ Country of Publication: England NLM ID: 9111626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-1438 (Electronic) Linking ISSN: 1048891X NLM ISO Abbreviation: Int J Gynecol Cancer Subsets: MEDLINE

مواضيع طبية MeSH: Endometrial Hyperplasia/*drug therapy , Endometrial Neoplasms/*drug therapy , Progestins/*administration & dosage, Biomarkers, Tumor ; Endometrial Hyperplasia/genetics ; Endometrial Neoplasms/classification ; Endometrial Neoplasms/genetics ; Female ; Humans ; Neoplasm Recurrence, Local/prevention & control ; Risk Factors

مستخلص: Objectives: This review examines how response rates to progestin treatment of low-grade endometrial cancer can be improved. In addition to providing a brief overview of the pathogenesis of low-grade endometrial cancer, we discuss limitations in the current classification of endometrial cancer and how stratification may be refined using molecular markers to reproducibly identify 'low-risk' cancers which may represent the best candidates for progestin therapy. We also discuss constraints in current approaches to progestin treatment of low-grade endometrial cancer and perform a systematic review of predictive biomarkers.
Methods: PubMed, ClinicalTrials.gov, and Cochrane Library were searched for studies reporting pre-treatment biomarkers associated with outcome in women with low-grade endometrial cancer or endometrial hyperplasia with an intact uterus who received progestin treatment. Studies of fewer than 50 women were excluded. The study protocol was registered in PROSPERO (ID 152374). A descriptive synthesis of pre-treatment predictive biomarkers reported in the included studies was conducted.
Results: Of 1908 records reviewed, 19 studies were included. Clinical features such as age or body mass index cannot predict progestin response. Lesions defined as 'low-risk' by FIGO criteria (stage 1A, grade 1) can respond well; however, the reproducibility and prognostic ability of the current histopathological classification system is suboptimal. Molecular markers can be reproducibly assessed, have been validated as prognostic biomarkers, and may inform patient selection for progestin treatment. DNA polymerase epsilon (POLE)-ultramutated tumors and a subset of p53 wild-type or DNA mismatch repair (MMR)-deficient tumors with 'low-risk' features (eg, progesterone and estrogen receptor-positive) may have improved response rates, though this needs to be validated.
Discussion: Molecular markers can identify cases which may be candidates for progestin treatment. More work is needed to validate these biomarkers and potentially identify new ones. Predictive biomarkers are anticipated to inform future research into progestin treatment of low-grade endometrial cancer and ultimately improve patient outcomes.
Competing Interests: Competing interests: DGH is a founder and Chief Medical Officer of Contextual Genomics, a for-profit company that provides genomic diagnostics and reporting to assist in cancer patient treatment.
(© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

المؤلفون: Kim SR; Gynecologic Oncology, University of Toronto, Toronto, Ontario, Canada., Pina A; Obstetrics and Gynaecology, Universite de Montreal, Montreal, Quebec, Canada., Albert A; Women's Health Research Institute, Vancouver, British Columbia, Canada., McAlpine JN; Division Gynecology Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada., Wolber R; Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Gilks B; Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Carey MS; Division Gynecology Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada., Kwon JS; Division Gynecology Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada janice.kwon@vch.ca.

المصدر: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society [Int J Gynecol Cancer] 2020 Jun; Vol. 30 (6), pp. 783-788. Date of Electronic Publication: 2020 Apr 30.

نوع المنشور: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: BMJ Country of Publication: England NLM ID: 9111626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-1438 (Electronic) Linking ISSN: 1048891X NLM ISO Abbreviation: Int J Gynecol Cancer Subsets: MEDLINE

مواضيع طبية MeSH: DNA Mismatch Repair*, Carcinoma, Endometrioid/*etiology , Neoplasms/*etiology, Aged ; British Columbia/epidemiology ; Carcinoma, Endometrioid/mortality ; Female ; Humans ; Middle Aged ; Neoplasms/mortality ; Prognosis ; Retrospective Studies

مستخلص: Objectives: Mismatch repair deficiency is observed in 25%-30% of all endometrial cancers. This can be detected by the absence of mismatch repair protein staining on immunohistochemistry, and is used as a screen for Lynch syndrome. Only 10% of women with mismatch repair deficiency have Lynch syndrome, but mismatch repair deficiency may still have prognostic significance. The objective of this study was to compare clinical outcomes between mismatch repair-deficient and mismatch repair-proficient low-risk endometrioid endometrial cancers (stage IA, grade 1 or 2).
Methods: This was a retrospective population-based cohort study of all low-risk endometrioid endometrial cancers (stage IA, grade 1 or 2) from the Vancouver Coastal Health Authority region from February 2011 to January 2016 that were assessed for mismatch repair deficiency. Any other histology, stage, or grade was excluded from the study. Primary outcome measures were progression-free survival and overall survival calculated using Kaplan-Meier method and log-rank tests. Cox proportional hazards model estimated the association between mismatch repair deficiency and recurrence and death after adjustment for covariates, expressed as hazard ratios (HRs). Secondary outcome measures were recurrence rates expressed per 100 person-years (p100py).
Results: There were 475 patients diagnosed with low-risk endometrioid endometrial cancer, including 131 with mismatch repair-deficient (27.6%) and 344 with mismatch repair-proficient (72.4%) tumors. Women with mismatch repair-deficient tumors had worse progression-free survival (24 months; p=0.0082) and higher recurrence rates (3.56 p100py) compared with those with mismatch repair-proficient tumors (27 months; 1.21 p100py, p=0.04). The absolute number of recurrences was overall low. There were 11 recurrences out of 131 mismatch repair-deficient cases (8.4%) and 14 out of 344 mismatch repair proficient cases (4.1%). After adjustment for age, lymphovascular space invasion status, adjuvant therapy, and post-operative grade, mismatch repair-deficient status remained associated with a higher risk of recurrence (HR 3.56, 95% CI 2.01 to 5.95). There was no significant difference in overall survival between mismatch repair groups (mismatch repair-proficient group 27.5 months vs 25.0 months in the deficient group) (HR 1.23, 95% CI 0.49 to 3.10).
Conclusion: In low-risk stage IA grade 1 or 2 endometrioid endometrial cancers, mismatch repair deficiency is associated with a higher recurrence rate than mismatch repair proficiency after adjustment for covariates, implying that mismatch repair deficiency reflects a different biology in endometrial cancer.
Competing Interests: Competing interests: None declared.
(© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

المؤلفون: Proctor L; Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada., Hoang L; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada., Moore J; Radiation Oncology, BC Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada., Thompson E; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada., Leung S; Genetic Pathology Evaluation Center, Vancouver General Hospital, Vancouver, British Columbia, Canada., Natesan D; Radiation Oncology, Duke University School of Medicine, Durham, North Carolina, USA., Chino J; Radiation Oncology, Duke University School of Medicine, Durham, North Carolina, USA., Gilks B; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada., McAlpine JN; Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada jessica.mcalpine@vch.ca.

المصدر: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society [Int J Gynecol Cancer] 2020 Jan; Vol. 30 (1), pp. 100-106. Date of Electronic Publication: 2019 Nov 25.

نوع المنشور: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: BMJ Country of Publication: England NLM ID: 9111626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-1438 (Electronic) Linking ISSN: 1048891X NLM ISO Abbreviation: Int J Gynecol Cancer Subsets: MEDLINE

مواضيع طبية MeSH: Carcinoma, Squamous Cell/*radiotherapy , Carcinoma, Squamous Cell/*virology , Human papillomavirus 16/*isolation & purification , Papillomavirus Infections/*pathology , Vulvar Neoplasms/*radiotherapy , Vulvar Neoplasms/*virology, Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Cohort Studies ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Papillomavirus Infections/metabolism ; Retrospective Studies ; Treatment Outcome ; Vulvar Neoplasms/metabolism ; Vulvar Neoplasms/pathology

مستخلص: Introduction: Vulvar squamous cell carcinoma develops through two separate pathways, associated with the presence or absence of high-risk human papilloma virus (HPV). The objective of this study was to evaluate treatment response and clinical outcomes in women with HPV-associated versus HPV-independent vulvar squamous cell carcinoma treated with primary radiation therapy, in order to determine the ability to use HPV status as a predictor of response to radiation therapy.
Methods: This was a retrospective cohort study combining data from British Columbia Cancer, Canada and Duke University, USA. Patients were included who had been treated with radiation therapy but excluded if they had received major surgical interventions. Immunohistochemistry for p16 (as a surrogate for high-risk HPV infection) and p53 was performed. We analyzed the univariable association between p16 status and clinico-pathological features and performed univariable survival analysis for p16.
Results: Forty-eight patients with vulvar squamous cell carcinoma treated with primary radiation therapy were identified: 26 p16 positive/HPV-associated patients and 22 p16 negative/HPV-independent patients. p16 positive vulvar squamous cell carcinoma demonstrated a significantly improved overall survival (HR 0.39, p=0.03) and progression-free survival (HR 0.35, p=0.02). In women treated with definitive radiation therapy, p16 positivity was associated with improved overall survival (HR 0.29, p<0.01) and progression-free survival (HR 0.21, p<0.01). Among patients who received sensitizing chemotherapy, a significant association was observed with p16 positive tumors and overall survival (HR 0.25, p=0.03) and progression-free survival (HR 0.09, p<0.01).
Conclusion: This study suggests that HPV status in vulvar squamous cell carcinoma has both prognostic and predictive implications, with increased radiosensitivity demonstrated in HPV-associated vulvar squamous cell carcinoma. Implications may include radiation dose de-escalation for HPV-associated vulvar squamous cell carcinoma and increased surgical aggressiveness for HPV-independent vulvar squamous cell carcinoma.
Competing Interests: Competing interests: None declared.
(© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

المؤلفون: Arora N; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada., Talhouk A; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada., McAlpine JN; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada., Law MR; Centre for Health Services and Policy Research, School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada., Hanley GE; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada Gillian.hanley@vch.ca.

المصدر: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society [Int J Gynecol Cancer] 2019 Mar; Vol. 29 (3), pp. 593-598. Date of Electronic Publication: 2018 Dec 21.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: BMJ Country of Publication: England NLM ID: 9111626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-1438 (Electronic) Linking ISSN: 1048891X NLM ISO Abbreviation: Int J Gynecol Cancer Subsets: MEDLINE

مواضيع طبية MeSH: Cancer Survivors/*statistics & numerical data , Carcinoma, Ovarian Epithelial/*mortality , Ovarian Neoplasms/*mortality, Adult ; Aged ; Aged, 80 and over ; British Columbia/epidemiology ; Cause of Death ; Cohort Studies ; Female ; Humans ; Middle Aged

مستخلص: Objectives: Little is known regarding the health of women who survive more than 5 years following their ovarian cancer diagnosis. To bridge an important gap in our knowledge about long term health of ovarian cancer survivors, we examined the causes of death among women diagnosed with epithelial ovarian cancer between 1990 and 2014 in British Columbia. These causes were stratified by years since diagnosis, and compared with age- standardized causes of death among women who have not been diagnosed with ovarian cancer.
Methods: We examined all women with epithelial ovarian cancer in British Columbia 1990-2014 using population- based administrative datasets. We stratified women into three groups: all epithelial ovarian cancer patients; women surviving 5 to 9 years post-diagnosis, and women surviving 10 or more years since diagnosis. All- cause and cause specific standardized mortality ratios (SMRs) were calculated.
Results: There were 4246 deaths among 6427 women with epithelial ovarian cancer. About 55.9% of deaths were from ovarian cancer. When compared with the general population, the highest SMRs (SMR of 5 or higher) were for deaths from other cancers and external causes (44.4% from falls) among women surviving 5-9 years and 10 or more years post-diagnosis. Mortality from other cancers can largely be explained by deaths from breast cancer (15.8%), lung cancer (12.3%), and colorectal cancer (11%).
Conclusions: While the majority of epithelial ovarian cancer patients continue to die from their ovarian cancer, our results suggest that long term ovarian cancer survivors are particularly vulnerable to deaths from other cancers and from falls in elderly survivors. These data could indicate closer surveillance for breast, lung, and colorectal cancer, and closer attention to bone health is warranted among women surviving for 5 or more years following their epithelial ovarian cancer diagnosis.
Competing Interests: Competing interests: None declared.
(© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

المؤلفون: Pina A; Department of Gynecology and Obstetrics, Division Gynecologic Oncology, Université de Montréal, Centre Hospitalier de l'Université de Montréal, Service de Gynécologie Oncologique, Montreal, Quebec., Wolber R; Department of Laboratory Medicine and Pathology, Lions Gate Hospital, North Vancouver., McAlpine JN; Division Gynecologic Oncology, Department of Gynecology and Obstetrics, and., Gilks B; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Kwon JS; Department of Laboratory Medicine and Pathology, Lions Gate Hospital, North Vancouver.

المصدر: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society [Int J Gynecol Cancer] 2018 Oct; Vol. 28 (8), pp. 1624-1630.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: BMJ Country of Publication: England NLM ID: 9111626 Publication Model: Print Cited Medium: Internet ISSN: 1525-1438 (Electronic) Linking ISSN: 1048891X NLM ISO Abbreviation: Int J Gynecol Cancer Subsets: MEDLINE

مواضيع طبية MeSH: Adenocarcinoma/*genetics , Adenocarcinoma/*metabolism , DNA Repair Enzymes/*biosynthesis , Endometrial Neoplasms/*genetics , Endometrial Neoplasms/*metabolism, Adenocarcinoma/pathology ; Adenocarcinoma/therapy ; Cohort Studies ; DNA Repair Enzymes/genetics ; DNA-Binding Proteins/biosynthesis ; DNA-Binding Proteins/genetics ; Endometrial Neoplasms/pathology ; Endometrial Neoplasms/therapy ; Female ; Germ-Line Mutation ; Humans ; Immunohistochemistry ; Middle Aged ; Mismatch Repair Endonuclease PMS2/biosynthesis ; Mismatch Repair Endonuclease PMS2/genetics ; MutL Protein Homolog 1/biosynthesis ; MutL Protein Homolog 1/genetics ; MutS Homolog 2 Protein/biosynthesis ; MutS Homolog 2 Protein/genetics ; Neoplasm Staging ; Retrospective Studies

مستخلص: Objective: There is uncertainty about the prognostic significance of mismatch repair (MMR) deficiency in endometrial cancer. The objective was to evaluate clinical characteristics and outcomes of endometrial cancers based on MMR status within a population-based study.
Methods: This was a retrospective population-based cohort study of all endometrial cancer cases from the Vancouver Coastal Health Authority region, evaluated for 4 MMR proteins using immunohistochemistry from 2012 to 2015. Patients were classified as MMR deficient (dMMR, any MMR protein absent) or MMR proficient (pMMR), Demographics, tumor characteristics, recurrences, and survival rates were compared according to MMR status.
Results: There were 892 patients, with 650 pMMR (72.5%) and 242 dMMR tumors. The dMMR group had more endometrioid tumors (87.6% vs 74.0%, P < 0.001), lymphovascular space invasion (43.8% vs 30.8%, P = 0.001), and dedifferentiation (5.9% vs 1.5%, P < 0.001), but fewer grade 1 tumors compared with the pMMR group (31.8% vs 40.8%, P < 0.001). Median progression-free survival and overall survival have not been reached. After a median follow-up of 31 months (1-99 months), there was no difference in progression or recurrence rates between pMMR and dMMR tumors (19.5% vs 16.5%; P = 0.31). However, among those with nonendometrioid tumors, recurrence and mortality rates were significantly higher for pMMR than dMMR tumors (42.0% vs 10.0%, P = 0.001, and 36.1% vs 13.1%, P = 0.01, respectively), despite similar stage and lymphovascular space invasion distributions.
Discussion: In this population-based study, there were no significant differences in recurrence or survival outcomes according to MMR status in endometrial cancer. However, among those with nonendometrioid tumors, there were lower recurrence and mortality rates associated with MMR-deficient compared with MMR-proficient tumors.