Clinicopathological significance of cancer stem-like cell markers in high-grade neuroendocrine carcinoma of the lung

Masahiro Morise, Tomoyuki Hishida, Akiko Takahashi, Junji Yoshida, Yuichiro Ohe, Kanji Nagai, Genichiro Ishii

Research output: Contribution to journalArticle

6 Citations (Scopus)


Purpose: This study aimed to evaluate the clinicopathological significance of cancer stem-like cell (CSLC) markers in high-grade neuroendocrine carcinoma (HGNEC) of the lung, including small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). Methods: We retrospectively studied patients who underwent surgical resection of SCLC (n = 60) and LCNEC (n = 45) to analyze their clinicopathological profiles and the immunohistochemical expression of putative CSLC markers (Caveolin, Notch, CD44, CD166, SOX2, ALDH1, and Musashi1). Staining scores for these markers in tumor cells were calculated by multiplying the percentage of positive tumor cells per lesion by the staining intensity level (0, 1, and 2); a score of ≥10 represented positive expression. Results: There was a difference between SCLC and LCNEC with respect to both SOX2 (55 vs. 27 %, p = 0.003) and CD166 (27 vs. 47 %, p = 0.034) expression. ALDH1 expression was equally observed in SCLC and LCNEC (67 vs. 73 %, p = 0.46), and patients with ALDH1-positive HGNEC had significantly worse recurrence-free survival (RFS) and overall survival (OS) rates than those with ALDH1-negative HGNEC (5-year RFS: 39 vs. 67 %, p = 0.009; 5-year OS: 50 vs. 79 %, p = 0.021). A multivariate analysis revealed that positive ALDH1 expression was an independent unfavorable prognostic factor with respect to both RFS and OS. Conclusions: The differences in the expression profiles of CSLC markers might reflect morphological differences between SCLC and LCNEC. Positive ALDH1 expression in lung HGNEC was associated with an unfavorable patient prognosis, which suggested that ALDH1-positive tumor cells might be future therapeutic targets for the treatment of lung HGNEC.

Original languageEnglish
Pages (from-to)2121-2130
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Issue number12
Publication statusPublished - 2015 May 12
Externally publishedYes



  • Aldehyde dehydrogenase 1 (ALDH1)
  • Cancer stem-like cells
  • High-grade neuroendocrine carcinoma
  • Large cell neuroendocrine carcinoma
  • Small cell lung carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this