Journal
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 141, Issue 12, Pages 2121-2130Publisher
SPRINGER
DOI: 10.1007/s00432-015-1985-3
Keywords
Cancer stem-like cells; High-grade neuroendocrine carcinoma; Small cell lung carcinoma; Large cell neuroendocrine carcinoma; Aldehyde dehydrogenase 1 (ALDH1)
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Funding
- Japan Society for the Promotion of Science [24791481]
- Grants-in-Aid for Scientific Research [24791481] Funding Source: KAKEN
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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). 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 a parts per thousand yen10 represented positive expression. 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. 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.
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