Prognostic implications of neuroendocrine differentiation and hormone production in patients with stage I nonsmall cell lung carcinoma

Giuseppe Pelosi, Felice Pasini, Angelica Sonzogni, Fausto Maffini, Patrick Maisonneuve, Antonio Iannucci, Alberto Terzi, Giovanni De Manzoni, Enrica Bresaola, Giuseppe Viale

Research output: Contribution to journalArticlepeer-review


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 ≥ 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.

Original languageEnglish
Pages (from-to)2487-2497
Number of pages11
Issue number10
Publication statusPublished - May 15 2003


  • Chromogranin A
  • Hormone
  • Immunohistochemistry
  • Neuroendocrine differentiation
  • Nonsmall cell lung carcinoma
  • Survival
  • Synaptophysin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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