Journal ArticleDOI
An algorithmic approach utilizing CK7, TTF1, beta-catenin, CDX2, and SSTR2A can help differentiate between gastrointestinal and pulmonary neuroendocrine carcinomas.
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In this article, a stepwise algorithmic approach utilizing CK7, TTF1, beta-catenin, CDX2, SSTR2A, SATB2, Napsin A, PR, GATA3, PAX8, ISL1, AFP, SMAD4, Rb, and p53 were used to distinguish primary GI-NEC from pulmonary neuroendocrine carcinoma.Abstract:
Primary gastrointestinal neuroendocrine carcinoma (GI-NEC) cannot be distinguished morphologically from pulmonary neuroendocrine carcinoma (P-NEC). This can present a significant diagnostic challenge in cases where site of origin cannot be readily determined. To identify immunohistochemical (IHC) markers that can be used to reliably distinguish between GI-NECs and P-NECs, we constructed 3-mm tissue microarrays, one containing 13 GI-NECs and one containing 20 P-NECs. IHC was performed on both microarrays using 21 stains: AE1/AE3, CK7, CK20, synaptophysin, chromogranin, CD56, INSM1, SSTR2A, CDX2, SATB2, TTF1, Napsin A, PR, GATA3, PAX8, ISL1, beta-catenin, AFP, SMAD4, Rb, and p53. For GI-NEC, the most strongly expressed marker was synaptophysin (mean H-score 248), while AE1/AE3 was the most strongly expressed in P-NEC (mean H-score 230), which was stronger than in GI-NEC (p = 0.011). Other markers that were stronger overall in P-NEC than in GI-NEC included CK7 (p < 0.0001) and TTF1 (p < 0.0001). Markers that were stronger overall in GI-NEC than in P-NEC included SSTR2A (p = 0.0021), SATB2 (p = 0.018), CDX2 (p = 0.019), and beta-catenin (nuclear; p = 0.029). SMAD4, Rb, and p53 showed similar rates of abnormal protein expression. Based on these results, a stepwise algorithmic approach utilizing CK7, TTF1, beta-catenin, CDX2, and SSTR2A had a 91% overall accuracy in distinguishing these GI-NEC from P-NEC. This was tested on a second cohort of 10 metastatic GI-NEC and 10 metastatic P-NEC, with an accuracy in this cohort of 85% and an overall accuracy of 89% for the 53 cases tested. Our algorithm reasonably discriminates GI-NEC from P-NEC using currently available IHC stains.read more
Citations
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Journal ArticleDOI
Second-Generation Neuroendocrine Immunohistochemical Markers: Reflections from Clinical Implementation.
TL;DR: In this paper, the advent of second-generation neuroendocrine markers ISL LIM Homeobox 1 (ISL1), INSM Transcriptional Repressor 1 (INSM1), and Secretagogin (SECG) have expanded the pathology toolbox considerably, constituting markers that often retain expression even in poorly differentiated neuroendocrin carcinomas.
Journal ArticleDOI
An update on the development of concepts, diagnostic criteria, and challenging issues for neuroendocrine neoplasms across different digestive organs
Anne Couvelard,Jérôme Cros +1 more
TL;DR: An update on diagnosis, including the most important differential diagnoses of NEN, with a focus on high-grade neoplasms and mixed tumours, and a variety of currently used and next-generation predictive and prognostic biomarkers as well as biomarkers of tumour origin are highlighted.
Journal ArticleDOI
Neuroendocrine Differentiation in Conventional Colorectal Adenocarcinomas: Incidental Finding or Prognostic Biomarker?
Björn Konukiewitz,Atsuko Kasajima,M. Schmitt,Kristina Schwamborn,Tanja Groll,Felix Schicktanz,Claire Delbridge,Lisa Marie Schütze,Dirk Wilhelm,Corinna Lang,Sebastian Lange,Sebastian Foersch,Paul Jank,Katja Steiger,Alexander von Werder,Carsten Denkert,Wilko Weichert,Günter Klöppel,Moritz Jesinghaus +18 more
TL;DR: In this article, the authors investigated synaptophysin expression in 1002 conventional colorectal adenocarcinomas and correlated the results with clinicopathological characteristics and patient survival.
Journal ArticleDOI
Primary hepatic neoplasms arising in cirrhotic livers can have a variable spectrum of neuroendocrine differentiation.
TL;DR: In this paper, the authors identified four cases of primary hepatic neoplasms with neuroendocrine differentiation, two females and two males with age ranging from 52 to 74 years.
References
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Book
WHO Classification of Tumours of the Digestive System
TL;DR: WHO Classification of Tumours of the Digestive System - Libros de Medicina - Gastroenterologia oncologica - 128,25
Journal ArticleDOI
Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States.
Arvind Dasari,Chan Shen,Daniel M. Halperin,Bo Zhao,Shouhao Zhou,Ying Xu,Tina Shih,James C. Yao +7 more
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Journal ArticleDOI
Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial
Howard L. Kaufman,Jeffery S. Russell,Omid Hamid,Shailender Bhatia,Patrick Terheyden,Sandra P. D'Angelo,Kent C. Shih,Céleste Lebbé,Gerald P. Linette,Michele Milella,Isaac Brownell,Karl D. Lewis,Jochen H. Lorch,Kevin M. Chin,Lisa Mahnke,Anja von Heydebreck,Jean Marie Cuillerot,Paul Nghiem +17 more
TL;DR: Treatment with avelumab was associated with durable responses, most of which are still ongoing, and was well tolerated; hence, a Velumab represents a new therapeutic option for advanced Merkel cell carcinoma.
Journal ArticleDOI
Comparisons between the National Comprehensive Cancer Network (NCCN) non‐small‐cell lung cancer (NSCLC) Clinical Practice Guidelines (Chinese version), the NCCN original edition, and the European Society for Medical Oncology NSCLC Guidelines in 2009
TL;DR: Comparison of the differences between NCCN non‐small‐cell lung cancer Clinical Practice Guidelines (Chinese version), the N CCN original edition, and European Society for Medical Oncology non-small‐ cell lung cancer guidelines is compared.
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