Putative Stem Cell Markers in Non–Small-Cell Lung Cancer: A Clinicopathologic Characterization

• Published in: Journal of thoracic oncology Vol. 9; no. 1; pp. 41 - 49
• Main Authors: Sterlacci, Willam, Savic, Spasenija, Fiegl, Michael, Obermann, Ellen, Tzankov, Alexandar
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2014; Copyright by the European Lung Cancer Conference and the International Association for the Study of Lung Cancer
• Subjects: AC133 Antigen; Adult; Aged; Antigens, CD - analysis; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; CD24 Antigen - analysis; Epithelial-Mesenchymal Transition; Female; Glycoproteins - analysis; Humans; Hyaluronan Receptors - analysis; Immunohistochemistry; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Markers; Middle Aged; Neoplastic Stem Cells - chemistry; Non–small-cell lung cancer; Peptides - analysis; Stem cells; Immunohistochemistry; Non–small-cell lung cancer; Stem cells; Markers
• ISSN: 1556-0864; 1556-1380; 1556-1380
• DOI: 10.1097/JTO.0000000000000021

The cancer stem cell (CSC) theory postulates the existence of a distinct population of undifferentiated cells responsible for tumor initiation and maintenance. CSCs may be naturally resistant to the cytotoxic effect of radio-chemotherapy because of slow cell cycling, lower proliferation, and increased expression of DNA repair and antiapoptosis genes. To date, a universal marker for CSCs has not been identified. Proposed CSC markers are expressed both by cancer cells as well as by benign stem cells. Although many putative CSC markers exist, a precise characterization for non–small-cell lung cancer (NSCLC) is lacking. We explored the expression of multiple alleged stemness associated markers in 371 surgically resected NSCLCs. Extensive clinical data and a postoperative follow-up period of up to 15 years enabled detailed clinicopathological correlations. ABCG5, ALDH1, CD24, CD44, CD133, CD166, epithelial cell adhesion molecule epitopes (ESA, MOC-31, Ber-EP4), nestin, OCT4, and sex-determining region Y-box 2 were analyzed immunohistochemically by using a standardized tissue microarray platform. Sex-determining region Y-box 2, CD44, ABCG5, ALDH1, and nestin were associated with poorer tumor differentiation and/or an increased proliferation index. ALDH1, CD44, and SOX2 were frequently found in squamous cell carcinoma, whereas CD24, CD166, and epithelial cell adhesion molecule markers were encountered in adenocarcinomas. CD44 expression was an independent marker associated with better overall survival in squamous cell carcinoma and Ber-EP4 was associated with tumor recurrences. The expression and prognostic significance of CSC markers obviously varies depending on histologic NSCLC subtype. Importantly, our findings suggest that CD44 and Ber-EP4 may be promising for ongoing targeted therapies in specific NSCLC subgroups.