BACKGROUND: Approximately 10-20% of nonsmall cell lung carcinomas (NSCLC) show neuroendocrine (NE) differentiation, as evaluated by panendocrine markers or ultrastructural evidence of dense-core secretory granules. However, little is known regarding the prevalence and clinical implications of NE differentiation in patients with Stage I NSCLC. METHODS: The authors analyzed 220 consecutive patients with Stage I NSCLC (pT1-T2N0M0) among 2100 patients with primary lung carcinoma who underwent surgical treatment between 1987 and 1993. Using light microscopy and immunohistochemical staining for synaptophysin, chromogranin A, and respiratory tract-related hormones, 28 NSCLC specimens with NE differentiation (NSCLC-ND) and 11 large cell neuroendocrine carcinoma (LCNEC) specimens were identified. RESULTS: The 28 NSCLC-ND specimens included 15 adenocarcinomas and 13 squamous cell carcinomas. Neoplastic cells with NE features never exceeded 20% in NSCLC-ND specimens, whereas neoplastic cells amounted to 20-90% in LCNEC specimens. NSCLC-ND specimens with > 5% NE-differentiated tumor cells showed increased Ki-67 labeling index (P = 0.007) and invasive phenotype, as evaluated by fascin immunoreactivity (P = 0.021). Patients with adenocarcinoma, but not with squamous cell carcinoma, who had > 5% NE-differentiated cells had a worse clinical course compared with patients who had ordinary NSCLC, with reduced overall survival (P = 0.017) and disease free survival (P = 0.049). In multivariate analysis, NE differentiation > 5% neoplastic cells in patients with adenocarcinoma independently predicted a poorer prognosis (hazard ratio, 2.61; 95% confidence interval, 0.99-6.85). Hormone production was restricted to chromogranin positive NSCLC-ND but did not affect prognosis. CONCLUSIONS: Stage I adenocarcinomas with >or= 5% NE tumor cells are clinically aggressive tumors, similar to LCNEC. Hormone production identifies a more fully developed neuroendocrine phenotype but is not relevant to prognosis. The identification of NE-differentiated cells in patients with NSCLC may have clinical relevance. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11376
BACKGROUND: Approximately 10-20% of nonsmall cell lung carcinomas (NSCLC) show neuroendocrine (NE) differentiation, as evaluated by panendocrine markers or ultrastructural evidence of dense-core secretory granules. However, little is known regarding the prevalence and clinical implications of NE differentiation in patients with Stage I NSCLC. METHODS: The authors analyzed 220 consecutive patients with Stage I NSCLC (pT1-T2N0M0) among 2100 patients with primary lung carcinoma who underwent surgical treatment between 1987 and 1993. Using light microscopy and immunohistochemical staining for synaptophysin, chromogranin A, and respiratory tract-related hormones, 28 NSCLC specimens with NE differentiation (NSCLC-ND) and 11 large cell neuroendocrine carcinoma (LCNEC) specimens were identified. RESULTS: The 28 NSCLC-ND specimens included 15 adenocarcinomas and 13 squamous cell carcinomas. Neoplastic cells with NE features never exceeded 20% in NSCLC-ND specimens, whereas neoplastic cells amounted to 20-90% in LCNEC specimens. NSCLC-ND specimens with > 5% NE-differentiated tumor cells showed increased Ki-67 labeling index (P = 0.007) and invasive phenotype, as evaluated by fascin immunoreactivity (P = 0.021). Patients with adenocarcinoma, but not with squamous cell carcinoma, who had > 5% NE-differentiated cells had a worse clinical course compared with patients who had ordinary NSCLC, with reduced overall survival (P = 0.017) and disease free survival (P = 0.049). In multivariate analysis, NE differentiation > 5% neoplastic cells in patients with adenocarcinoma independently predicted a poorer prognosis (hazard ratio, 2.61; 95% confidence interval, 0.99-6.85). Hormone production was restricted to chromogranin positive NSCLC-ND but did not affect prognosis. CONCLUSIONS: Stage I adenocarcinomas with >or= 5% NE tumor cells are clinically aggressive tumors, similar to LCNEC. Hormone production identifies a more fully developed neuroendocrine phenotype but is not relevant to prognosis. The identification of NE-differentiated cells in patients with NSCLC may have clinical relevance. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11376
Authors: Adi F Gazdar; Trisha K Savage; Jane E Johnson; Anton Berns; Julien Sage; R Ilona Linnoila; David MacPherson; David G McFadden; Anna Farago; Tyler Jacks; William D Travis; Elisabeth Brambilla Journal: J Thorac Oncol Date: 2015-04 Impact factor: 15.609
Authors: Ilya V Demidyuk; Andrey V Shubin; Eugene V Gasanov; Alexander M Kurinov; Vladimir V Demkin; Tatyana V Vinogradova; Marina V Zinovyeva; Alexander V Sass; Irina B Zborovskaya; Sergey V Kostrov Journal: PLoS One Date: 2013-02-07 Impact factor: 3.240