دورية أكاديمية
Stage IV lung carcinoids: spectrum and evolution of proliferation rate, focusing on variants with elevated proliferation indices.
العنوان: | Stage IV lung carcinoids: spectrum and evolution of proliferation rate, focusing on variants with elevated proliferation indices. |
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المؤلفون: | Rekhtman N; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. rekhtman@mskcc.org., Desmeules P; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pathology, Quebec Heart and Lung Institute, Quebec, QC, Canada., Litvak AM; Thoracic Oncology Service, Department of Medicine, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Cancer Center at Saint Barnabas Medical Center, Livingston, NJ, USA., Pietanza MC; Thoracic Oncology Service, Department of Medicine, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Merck Research Laboratories, Rahway, NJ, USA., Santos-Zabala ML; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ni A; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Montecalvo J; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chang JC; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Beras A; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Preeshagul IR; Thoracic Oncology Service, Department of Medicine, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Sabari JK; Thoracic Oncology Service, Department of Medicine, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; New York University Langone's Perlmutter Cancer Center, New York, NY, USA., Rudin CM; Thoracic Oncology Service, Department of Medicine, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ladanyi M; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Klimstra DS; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Travis WD; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Lai WC; Thoracic Oncology Service, Department of Medicine, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. |
المصدر: | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2019 Jul; Vol. 32 (8), pp. 1106-1122. Date of Electronic Publication: 2019 Mar 28. |
نوع المنشور: | Comparative Study; Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
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 |
أسماء مطبوعة: | Publication: 2023- : [New York] : Elsevier Inc. Original Publication: Baltimore, MD : Williams & Wilkins, c1988- |
مواضيع طبية MeSH: | Cell Proliferation* , Mitosis*, Carcinoid Tumor/*secondary , Lung Neoplasms/*pathology , Neuroendocrine Tumors/*secondary, Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics ; Carcinoid Tumor/chemistry ; Carcinoid Tumor/genetics ; Diagnosis, Differential ; Disease Progression ; Female ; Humans ; Ki-67 Antigen/analysis ; Lung Neoplasms/chemistry ; Lung Neoplasms/genetics ; Male ; Middle Aged ; Mitotic Index ; Neoplasm Staging ; Neuroendocrine Tumors/chemistry ; Neuroendocrine Tumors/genetics ; Predictive Value of Tests |
مستخلص: | The spectrum and evolution of proliferation rates in stage IV lung carcinoids is poorly defined. In particular, there are limited data on the prevalence and characteristics of tumors exceeding the standard upper proliferative criteria-as defined largely based on early-stage carcinoids-in metastatic setting. Sixty-six patients with stage IV lung carcinoids were identified, and all evaluable samples (n = 132; mean 2 samples per patient) were analyzed for mitotic counts and Ki-67 rate. Clinicopathologic and genomic features associated with elevated proliferation rates (>10 mitoses per 2 mm 2 and/or >20% hot-spot Ki-67), and evolution of proliferation rates in serial specimens were analyzed. We found that mitoses and/or Ki-67 exceeded the standard criteria in 35 of 132 (27%) samples, primarily (31/35 cases) at metastatic sites. Although neuroendocrine neoplasms with >10 mitoses per 2 mm 2 are currently regarded as de facto neuroendocrine carcinomas, the notion that these cases are part of the spectrum of carcinoids was supported by (1) well-differentiated morphology, (2) conventional proliferation rates in other samples from same patient, (3) genetic characteristics, including the lack of RB1/TP53 alterations in all tested samples (n = 19), and (4) median overall survival of 2.7 years, compared to <1 year survival of stage IV neuroendocrine carcinomas in the historic cohorts. In patients with matched primary/metastatic specimens (48 pairs), escalation of mitoses or Ki-67 by ≥10 points was observed in 35% of metastatic samples; clonal relationship in one pair with marked proliferative progression was confirmed by next-generation sequencing. Notably, escalation of proliferation rate was documented in a subset of metastases arising from resected typical carcinoids, emphasizing that the diagnosis of typical carcinoid in primary tumor does not assure low proliferation rate at metastatic sites. In conclusion, stage IV lung carcinoids frequently exceed the standard proliferative criteria established for primary tumors, and commonly exhibit proliferative escalation at metastatic sites. Despite the overlap of proliferation rates, these tumors show fundamental morphologic, genomic and clinical differences from neuroendocrine carcinomas, and should be classified separately from those tumors. Awareness of the increased proliferative spectrum in metastatic carcinoids is critical for their accurate diagnosis. Further studies are warranted to explore the impact of proliferation indices on prognosis and therapeutic responses of patients with metastatic carcinoids. |
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معلومات مُعتمدة: | P30 CA008748 United States CA NCI NIH HHS |
المشرفين على المادة: | 0 (Biomarkers, Tumor) 0 (Ki-67 Antigen) 0 (MKI67 protein, human) |
تواريخ الأحداث: | Date Created: 20190330 Date Completed: 20200427 Latest Revision: 20240720 |
رمز التحديث: | 20240720 |
مُعرف محوري في PubMed: | PMC6746332 |
DOI: | 10.1038/s41379-019-0248-2 |
PMID: | 30923345 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1530-0285 |
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DOI: | 10.1038/s41379-019-0248-2 |