A subset of small cell lung cancer with low neuroendocrine expression and good prognosis: a comparison study of surgical and inoperable cases with biopsy

Hum Pathol. 2014 May;45(5):1045-56. doi: 10.1016/j.humpath.2014.01.001. Epub 2014 Jan 23.

Abstract

Patients with small cell lung carcinoma (SCLC) rarely demonstrate long-term survival. We previously reported that gene expression profiling identified a subset of SCLC with good prognosis in surgical cases. To find an easier way to routinely identify SCLC belonging to this subset, we conducted the present study with a hypothesis that neuroendocrine (NE) or basaloid (BA) phenotypes may influence prognosis. To confirm the subset, we used an array platform to analyze fresh samples. Because inoperable cases may differ from surgical cases, we enrolled 51 biopsy cases and 43 resected samples. To evaluate NE and BA phenotypes, we used NE (synaptophysin, chromogranin A, and CD56) and BA (p63 and CK34βE12) markers. To varying extents, expression profiling based on the array platform duplicated the subsets. For NE phenotypes, 77% of surgical cases and 100% of biopsy cases were positive for at least 1 marker. For BA phenotypes, only 19% of surgical cases were positive for at least 1 marker, whereas there were no positive biopsy cases. Cases undergoing surgery were categorized based on NE and BA immunoreactivity; 58% into NE+BA-, 19% into NE+BA+, 23% into NE-BA-, and 0 into NE-BA+ groups. NE- patients (n = 10) demonstrated a significantly better prognosis (P = .0306) than their NE+ counterparts (n = 33), whereas no survival difference was evident between the BA+ and BA- groups. Multivariate analyses showed that NE positivity was an independent prognostic factor. In conclusion, the SCLC subset with good prognosis is identified by low NE marker expression, which was found only in surgical cases.

Keywords: Basal cell; Immunohistochemistry; Neuroendocrine; Prognosis; Small cell lung cancer (SCLC).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis
  • Biopsy
  • CD56 Antigen / analysis
  • Carcinoma, Neuroendocrine / pathology
  • Chromogranin A / analysis
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Keratins / analysis
  • Lung Neoplasms / mortality
  • Male
  • Membrane Proteins / analysis
  • Middle Aged
  • Prognosis
  • Protein Array Analysis
  • Small Cell Lung Carcinoma / chemistry*
  • Small Cell Lung Carcinoma / pathology
  • Small Cell Lung Carcinoma / surgery*
  • Synaptophysin / analysis

Substances

  • Biomarkers, Tumor
  • CD56 Antigen
  • CKAP4 protein, human
  • Chromogranin A
  • Membrane Proteins
  • NCAM1 protein, human
  • Synaptophysin
  • Keratins