المؤلفون: Saad RS; Department of Pathology, Allegheny General Hospital/Drexel University College of Medicine, Pittsburgh, PA 15212, USA. rsaad@wpahs.org, Denning KL, Finkelstein SD, Liu Y, Pereira TC, Lin X, Silverman JF

المصدر: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2008 Oct; Vol. 21 (10), pp. 1200-7. Date of Electronic Publication: 2008 May 09.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 8806605 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0285 (Electronic) Linking ISSN: 08933952 NLM ISO Abbreviation: Mod Pathol Subsets: MEDLINE

مواضيع طبية MeSH: Loss of Heterozygosity*, Breast Neoplasms/*genetics , Carcinoma, Ductal, Breast/*genetics , Genetic Markers/*genetics , Neoplasms, Multiple Primary/*genetics, Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Ductal, Breast/secondary ; DNA Mutational Analysis ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; Microsatellite Repeats ; Middle Aged ; Neoplasms, Multiple Primary/metabolism ; Neoplasms, Multiple Primary/pathology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Steroid/metabolism

مستخلص: Histologic criteria have a limited role in determining whether the synchronous bilateral breast carcinomas represent two primaries or a metastasis to the contralateral breast. We studied the molecular analysis of synchronous bilateral breast carcinoma and whether they are originating from a single or different clone. We examined 17 patients with breast carcinoma, including 12 patients with synchronous bilateral carcinomas and control group of 5 infiltrating ductal carcinomas with regional lymph node metastases. Mutations were quantitatively determined to detect loss of heterozygosity (LOH) and microsatellite size alterations for a broad panel of 15 markers, involving 10 chromosomes using polymerase chain reaction. The carcinomas were classified as de novo or metastasis based on three levels of concordance: (1) marker-affected tumors were considered concordant if 50% or more of the same markers were mutated, (2) same gene copy affected, and (3) temporal sequence of mutation acquisition. In synchronous bilateral breast carcinoma patients, molecular analysis showed discordant mutations in all cases, supporting the diagnosis of de novo bilateral primary breast carcinomas. In patients with lymph node metastases, the primary breast carcinoma and metastases shared the same mutations, revealing a metastatic lesion. In conclusion, the application of molecular technology may play an important role for the differential diagnosis of dual primary carcinomas vs a metastatic breast cancer to contralateral breast. In this study, synchronous bilateral breast cancers represent two independent primaries rather than metastatic events.

المؤلفون: Nofech-Mozes S; Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada. Sharon.nofech-mozes@sunnybrook.ca, Khalifa MA, Ismiil N, Saad RS, Hanna WM, Covens A, Ghorab Z

المصدر: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2008 Sep; Vol. 21 (9), pp. 1147-55. Date of Electronic Publication: 2008 Jun 20.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 8806605 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0285 (Electronic) Linking ISSN: 08933952 NLM ISO Abbreviation: Mod Pathol Subsets: MEDLINE

مواضيع طبية MeSH: Cystadenocarcinoma, Serous/*diagnosis , Genital Neoplasms, Female/*diagnosis, Aged ; Antibodies, Monoclonal/metabolism ; Antibodies, Monoclonal, Murine-Derived ; Biomarkers, Tumor/metabolism ; Cystadenocarcinoma, Serous/metabolism ; Female ; Genital Neoplasms, Female/metabolism ; Humans ; Immunophenotyping ; Keratin-5/metabolism ; Keratin-6/metabolism ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism

مستخلص: To update the data on the expression of 'mesothelioma markers' by serous carcinomas of various sites we have studied cases from ovary (n=56), endometrium (n=37), fallopian tube (n=6), primary peritoneum (n=5) and cervix (n=3) using a panel of antibodies (WT1, P53, estrogen receptors, HER2/neu, D2-40, cytokeratin 5/6 and E-cadherin). Ovarian carcinomas demonstrated D2-40 and cytokeratin 5/6 immunoreactivity in 23.2 and 55.4% of cases, respectively. Endometrial carcinomas demonstrated D2-40 and cytokeratin 5/6 immunoreactivity in 43.2 and 37.8% of cases, respectively. D2-40 staining pattern was predominantly focal; however, strong reactivity was identified in 16.2% of endometrial and 10.7% of ovarian carcinomas. HER2/neu oncoprotein overexpression was demonstrated in 7 of 37 (18.9%) uterine serous carcinomas. In contrast, all the serous carcinomas of the other sites were HER2/neu negative. The proportion of positive cases was significantly different in ovarian vs endometrial carcinomas regarding WT1 (P=0.0458), estrogen receptors (P<0.001) reactivity and HER2/neu overexpression (P=0.0025). D2-40 and cytokeratin 5/6 are expressed in a considerable proportion of serous carcinomas and should be used cautiously in a 'mesothelioma panel' in situations where serous carcinoma is in the differential diagnosis. HER2/neu was exclusively overexpressed in serous carcinomas of endometrial origin.

المؤلفون: Saad RS; Department of Pathology, Allegheny General Hospital/Drexel University College of Medicine, Pittsburgh, PA 15213, USA. rsaad@wpahs.org, Kordunsky L, Liu YL, Denning KL, Kandil HA, Silverman JF

المصدر: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2006 Oct; Vol. 19 (10), pp. 1317-23. Date of Electronic Publication: 2006 Jun 23.

نوع المنشور: Comparative Study; Journal Article

بيانات الدورية: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 8806605 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0893-3952 (Print) Linking ISSN: 08933952 NLM ISO Abbreviation: Mod Pathol Subsets: MEDLINE

مواضيع طبية MeSH: Biomarkers, Tumor/*analysis , Colorectal Neoplasms/*pathology , Liver Neoplasms/*secondary , Lymphatic Vessels/*pathology, Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/analysis ; Antibodies, Monoclonal, Murine-Derived ; Antigens, Neoplasm/analysis ; Colorectal Neoplasms/chemistry ; Female ; Humans ; Lymphatic Metastasis ; Lymphatic Vessels/chemistry ; Male ; Middle Aged ; Neoplasm Invasiveness ; Platelet Endothelial Cell Adhesion Molecule-1/analysis ; Prognosis ; Retrospective Studies ; Vascular Endothelial Growth Factor A/analysis

مستخلص: Lymph node metastases is an important prognostic indicator for disease progression and crucial for therapeutic strategies in the work-up of colorectal carcinoma. In this study, we investigated tumor lymphangiogenesis and vascular endothelial growth factor (VEGF) expression as predictive markers for the risk of lymph node metastasis and their relation to other prognostic parameters in colorectal carcinoma. Resected colorectal carcinomas from 90 patients were examined, including 30 patients without lymph node metastases, 30 with only lymph node metastases, and 30 with liver metastases. Cases were immunostained for CD31, D2-40, and VEGF. Positivity stained microvessels were counted in densely vascular/lymphatic foci (hot spots) at x 400 field (=0.17 mm2). Intensity of staining for VEGF was scored on a two-tiered scale. D2-40 lymphatic microvessel density demonstrated significant correlation with CD31 counts (20+/-9 vs 18+/-6/0.17 mm2 field, P<0.05) and VEGF expression (P<0.01). VEGF was expressed in 61/90 (67%) cases. D2-40 identified lymphatic tumor invasion in 48/90 patients, which was greater than CD31 (37/90) and hematoxylin and eosin (H&E) (31/90). There was a positive significant correlation of D2-40, CD31 counts, and VEGF expression with the presence of lymphovascular invasion and lymph node metastases (P<0.05). D2-40 lymphatic microvessel density correlated significantly with depth of invasion (pT), positive vascular pedicle lymph nodes and liver metastases (P<0.05). In conclusion, D2-40 lymphatic microvessel density showed prognostic significance with positive correlation with lymphovascular invasion, pT, and metastases to lymph nodes and liver. Immunostaining with D2-40 enhances the detection of lymphatic invasion relative to H&E staining and the endothelial marker, CD31.

المؤلفون: Saad RS; Department of Pathology, Allegheny General Hospital, Pittsburgh, PA, USA. redasaad2@hotmail.com, Liu Y, Han H, Landreneau RJ, Silverman JF

المصدر: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2004 Oct; Vol. 17 (10), pp. 1235-42.

نوع المنشور: Comparative Study; Journal Article

بيانات الدورية: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 8806605 Publication Model: Print Cited Medium: Print ISSN: 0893-3952 (Print) Linking ISSN: 08933952 NLM ISO Abbreviation: Mod Pathol Subsets: MEDLINE

مواضيع طبية MeSH: Adenocarcinoma/*pathology , Adenocarcinoma, Bronchiolo-Alveolar/*pathology , Biomarkers, Tumor/*biosynthesis , Lung Neoplasms/*pathology, Adenocarcinoma/metabolism ; Adenocarcinoma, Bronchiolo-Alveolar/metabolism ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/metabolism ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/biosynthesis ; Survival Analysis ; Tumor Suppressor Protein p53/biosynthesis ; Vascular Endothelial Growth Factor A/biosynthesis

مستخلص: In this study, we investigated the prognostic value of HER2/neu, p53, and vascular endothelial growth factor in early stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung. We studied 100 patients and consisted of 50 cases with conventional adenocarcinoma and 50 cases with bronchioloalveolar carcinoma (32 nonmucinous and 18 mucinous subtypes). Representative sections were immunostained for HER2/neu, p53, and vascular endothelial growth factor. Positivity was scored quantitatively by three observers and correlated with multiple prognostic parameters including survival. In the conventional adenocarcinoma, HER2/neu, p53, and vascular endothelial growth factor were expressed in 19/50 (38%), 32/50 (64%), 33/50 (66%), respectively. In this group, p53 showed a significant correlation with recurrence while vascular endothelial growth factor correlated with angiolymphatic invasion (P < 0.05). HER2/neu, p53, and vascular endothelial growth factor expression was associated with significantly shorter survival (log rank, P < 0.05). Patient whose tumors coexpressed both p53 and HER2/neu had the worst outcome. In the bronchioloalveolar carcinoma, HER2/neu, p53, and vascular endothelial growth factor were expressed in 9/50 (18%), 3/50 (6%) and 12/50 (24%), respectively which was significantly less than in conventional adenocarcinoma (P < 0.05). HER2/neu positivity showed a significant correlation with shorter survival (log rank, P < 0.05) in nonmucinous type. In conclusion, vascular endothelial growth factor was associated with angiolymphatic invasion and poor prognosis in conventional adenocarcinoma. Also, in conventional adenocarcinoma, p53, and HER2/neu expression appeared to be poor prognostic markers, while in bronchioloalveolar carcinoma, only HER2/neu was associated with a poorer prognosis. This immunostaining pattern suggests that conventional adenocarcinoma has different molecular abnormalities than bronchioloalveolar carcinoma.

المؤلفون: Liu Y; Department of Pathology and Laboratory Medicine, Allegheny General Hospital, Pittsburgh, PA 15212, USA. yliu@wpahs.org, Sturgis CD, Bunker M, Saad RS, Tung M, Raab SS, Silverman JF

المصدر: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2004 Sep; Vol. 17 (9), pp. 1129-33.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 8806605 Publication Model: Print Cited Medium: Print ISSN: 0893-3952 (Print) Linking ISSN: 08933952 NLM ISO Abbreviation: Mod Pathol Subsets: MEDLINE

مواضيع طبية MeSH: Keratins/*biosynthesis , Meningeal Neoplasms/*pathology , Meningioma/*pathology, Antibodies, Neoplasm/analysis ; Biomarkers, Tumor/analysis ; Carcinoembryonic Antigen/analysis ; Carcinoma/metabolism ; Carcinoma/secondary ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Lewis X Antigen/analysis ; Meningeal Neoplasms/metabolism ; Meningioma/metabolism ; Mucin-1/analysis ; Predictive Value of Tests ; Vimentin/analysis

مستخلص: Based on clinical and histologic features, differentiating metastatic carcinomas from benign or malignant meningiomas usually is not difficult. Occasionally, however, in some patients without a clinical history of carcinoma, malignant meningiomas can morphologically simulate metastatic carcinoma, necessitating an immunohistochemical study for cytokeratin to make a correct diagnosis. However, the utility of immunohistochemical markers to separate malignant meningioma from metastatic carcinoma has not been investigated. The immunoperoxidase method with antigen retrieval was used to characterize the expression of three cytokeratins (AE1/AE3, CAM 5.2, and Pan cytokeratin), EMA, CEA, Ber-EP4, CD 15, and B72.3 in 12 previously diagnosed malignant meningiomas, 20 benign meningiomas, and 20 metastatic carcinomas. Cytokeratin expression was detected in 75% of malignant meningiomas, 0% of benign meningiomas, and 100% of metastatic carcinomas. While epithelial markers of Ber-EP4, CEA, B72.3 and CD-15 were positive in 90, 80, 70 and 65% of the metastatic carcinoma, respectively, they were negative in all 12 malignant meningioma examined. Vimentin immunoreactivity was seen in all benign and malignant meningiomas, and in 20% of metastatic carcinomas. Our results indicated that cytokeratin is not a reliable immunohistochemical marker to separate a malignant meningioma from metastatic carcinoma. A panel of epithelial markers including Ber-EP4, CEA, B72.3 and CD-15, and vimentin may be needed to separate malignant meningioma from metastatic carcinoma. Cytokeratin expression can be a potential pitfall for confusing a malignant meningioma with a metastatic carcinoma.

المؤلفون: Saad RS; Department of Pathology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA. redasaad2@hotmail.com, Liu YL, Nathan G, Celebrezze J, Medich D, Silverman JF

المصدر: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2004 Feb; Vol. 17 (2), pp. 197-203.

نوع المنشور: Comparative Study; Journal Article

بيانات الدورية: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 8806605 Publication Model: Print Cited Medium: Print ISSN: 0893-3952 (Print) Linking ISSN: 08933952 NLM ISO Abbreviation: Mod Pathol Subsets: MEDLINE

مواضيع طبية MeSH: Biomarkers, Tumor/*analysis , Colorectal Neoplasms/*metabolism , Colorectal Neoplasms/*pathology , Vascular Cell Adhesion Molecule-1/*biosynthesis , Vascular Endothelial Growth Factor A/*biosynthesis, Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; Colorectal Neoplasms/blood supply ; Endoglin ; Female ; Humans ; Immunohistochemistry ; Liver Neoplasms/secondary ; Lymphatic Metastasis/pathology ; Male ; Middle Aged ; Neovascularization, Pathologic/metabolism ; Prognosis ; Receptors, Cell Surface ; Retrospective Studies

مستخلص: Endoglin (CD105) has been shown to be a more useful marker to identify proliferating endothelium involved in tumor angiogenesis than panendothelial markers such as CD31. We investigated endoglin and vascular endothelial growth factor expression as possible prognostic markers in colorectal cancer. Surgical specimens from 150 patients with resected colorectal carcinomas were immunostained for endoglin, CD31 and vascular endothelial growth factor. Colorectal carcinoma cases consisted of 50 cases without lymph node metastases, 50 cases with only lymph node metastases and 50 cases with liver metastases (38 cases also had positive lymph nodes). Positively stained microvessels were counted in densely vascular foci (hot spots) at x 400 fields in each specimen. For vascular endothelial growth factor, intensity of staining was scored on a three-tiered scale. Results were correlated with other prognostic parameters. Endoglin demonstrated significantly more proliferating neoplastic microvessels than CD31 (31+/-10 vs 19+/-8/0.15 mm2 field, P<0.001). Low vascular endothelial growth factor expression within tumor cells was seen in 49 (33%) and high expression in 101 cases (67%). There was a positive correlation of endoglin, CD31 counts and vascular endothelial growth factor overexpression with the presence of angiolymphatic invasion and lymph node metastases (P<0.05). Only endoglin counts correlated significantly with liver metastases and positive vascular pedicle lymph nodes (P<0.05), while vascular endothelial growth factor showed significant correlation with the depth of invasion (P<0.01). Endoglin, by staining higher numbers of the proliferating vessels in colon carcinoma, is a more specific and sensitive marker for tumor angiogenesis than the commonly used panendothelial markers. Endoglin staining also showed prognostic significance with positive correlation with angiolymphatic invasion and metastases to lymph nodes and liver.