BACKGROUND: The terms large cell and mixed small-large cell neuroendocrine carcinoma (LCNC, MNC) have been proposed to describe distinct types of high-grade neuroendocrine lung tumors. However, cytologic appearance and neuroendocrine immunohistochemical stains cannot uniformly distinguish these from other neuroendocrine tumors, such as typical and atypical carcinoids or small cell carcinoma, or nonendocrine lung cancers such as large cell undifferentiated carcinoma. This study sought to determine the patterns of expression in LCNC and MNC of several molecular markers often abnormally expressed in lung cancers. METHODS: Primary lung tumors with neuroendocrine features operated on between 1984 and 1994 were reviewed and classified as typical carcinoid (TC), atypical carcinoid (AC), LCNC, MNC, and small cell lung cancer (SCLC) based on mitotic rate, extent of necrosis, and cytoarchitectural features. Immunohistochemistry was performed using antibodies MIB-1 for Ki67, pAb1801 for p53, OP-66 for Rb, 31G7 for EGFR. Staining was scored as 0 to 4+ (0 = less than 5%, 1+ = 5% to 20%, 2+ = 20% to 50%, 3+ = 50% to 80%, 4+ = more than 80%) for p53, Ki67, and EGFR; and negative, focal, or positive for Rb. Overall survival was calculated by the Kaplan-Meier method and prognostic factors compared by log rank test. RESULTS: Ninety-two tumors were examined: 25 TC, 7 AC, 24 LCNC, 18 MNC, 18 SCLC. The LCNC and MNC presented more frequently as stage II or III tumors (n = 28, 66%) than TC and AC (n = 5, 15%). Median survival for LCNC and MNC was 18.7 months, for SCLC 14.3 months, and has not been reached for TC and AC tumors. TC and AC tumors were uniformly characterized by low proliferative rate, absent p53, and normal Rb staining. LCNC, MNC, and SCLC showed a high proliferative rate, abnormal p53, and absent Rb staining. Overexpression of EGFR was frequent in all five tumor types. CONCLUSIONS: (1) Ki67, p53, and Rb help distinguish LCNC and MNC from TC and AC. (2) Small numbers of patients preclude comparison of survival rates, but LCNC/MNC have a median survival similar to comparable early stage SCLC, and clearly worse than TC/AC. These results justify a sharp separation of high-grade neuroendocrine tumors from carcinoids, and suggest a close relationship between LCNC, MNC, and SCLC.
BACKGROUND: The terms large cell and mixed small-large cell neuroendocrine carcinoma (LCNC, MNC) have been proposed to describe distinct types of high-grade neuroendocrine lung tumors. However, cytologic appearance and neuroendocrine immunohistochemical stains cannot uniformly distinguish these from other neuroendocrine tumors, such as typical and atypical carcinoids or small cell carcinoma, or nonendocrine lung cancers such as large cell undifferentiated carcinoma. This study sought to determine the patterns of expression in LCNC and MNC of several molecular markers often abnormally expressed in lung cancers. METHODS:Primary lung tumors with neuroendocrine features operated on between 1984 and 1994 were reviewed and classified as typical carcinoid (TC), atypical carcinoid (AC), LCNC, MNC, and small cell lung cancer (SCLC) based on mitotic rate, extent of necrosis, and cytoarchitectural features. Immunohistochemistry was performed using antibodies MIB-1 for Ki67, pAb1801 for p53, OP-66 for Rb, 31G7 for EGFR. Staining was scored as 0 to 4+ (0 = less than 5%, 1+ = 5% to 20%, 2+ = 20% to 50%, 3+ = 50% to 80%, 4+ = more than 80%) for p53, Ki67, and EGFR; and negative, focal, or positive for Rb. Overall survival was calculated by the Kaplan-Meier method and prognostic factors compared by log rank test. RESULTS: Ninety-two tumors were examined: 25 TC, 7 AC, 24 LCNC, 18 MNC, 18 SCLC. The LCNC and MNC presented more frequently as stage II or III tumors (n = 28, 66%) than TC and AC (n = 5, 15%). Median survival for LCNC and MNC was 18.7 months, for SCLC 14.3 months, and has not been reached for TC and ACtumors. TC and ACtumors were uniformly characterized by low proliferative rate, absent p53, and normal Rb staining. LCNC, MNC, and SCLC showed a high proliferative rate, abnormal p53, and absent Rb staining. Overexpression of EGFR was frequent in all five tumor types. CONCLUSIONS: (1) Ki67, p53, and Rb help distinguish LCNC and MNC from TC and AC. (2) Small numbers of patients preclude comparison of survival rates, but LCNC/MNC have a median survival similar to comparable early stage SCLC, and clearly worse than TC/AC. These results justify a sharp separation of high-grade neuroendocrine tumors from carcinoids, and suggest a close relationship between LCNC, MNC, and SCLC.
Authors: Olca Basturk; Laura Tang; Ralph H Hruban; Volkan Adsay; Zhaohai Yang; Alyssa M Krasinskas; Efsevia Vakiani; Stefano La Rosa; Kee-Taek Jang; Wendy L Frankel; Xiuli Liu; Lizhi Zhang; Thomas J Giordano; Andrew M Bellizzi; Jey-Hsin Chen; Chanjuan Shi; Peter Allen; Diane L Reidy; Christopher L Wolfgang; Burcu Saka; Neda Rezaee; Vikram Deshpande; David S Klimstra Journal: Am J Surg Pathol Date: 2014-04 Impact factor: 6.394
Authors: Tina Zahel; Sabine Krysa; Esther Herpel; Albrecht Stenzinger; Benjamin Goeppert; Peter Schirmacher; Hans Hoffmann; Philipp A Schnabel; Arne Warth Journal: Virchows Arch Date: 2012-03 Impact factor: 4.064
Authors: Jarushka Naidoo; Maria L Santos-Zabala; Tunc Iyriboz; Kaitlin M Woo; Camelia S Sima; John J Fiore; Mark G Kris; Gregory J Riely; Piro Lito; Afsheen Iqbal; Stephen Veach; Stephanie Smith-Marrone; Inderpal S Sarkaria; Lee M Krug; Charles M Rudin; William D Travis; Natasha Rekhtman; Maria C Pietanza Journal: Clin Lung Cancer Date: 2016-01-21 Impact factor: 4.785
Authors: Natasha Rekhtman; Maria C Pietanza; Matthew D Hellmann; Jarushka Naidoo; Arshi Arora; Helen Won; Darragh F Halpenny; Hangjun Wang; Shaozhou K Tian; Anya M Litvak; Paul K Paik; Alexander E Drilon; Nicholas Socci; John T Poirier; Ronglai Shen; Michael F Berger; Andre L Moreira; William D Travis; Charles M Rudin; Marc Ladanyi Journal: Clin Cancer Res Date: 2016-03-09 Impact factor: 12.531
Authors: A Faggiano; G Mansueto; P Ferolla; F Milone; M L del Basso de Caro; G Lombardi; A Colao; G De Rosa Journal: J Endocrinol Invest Date: 2008-03 Impact factor: 4.256