Cancer-initiating cell marker-positive cells generate metastatic tumors that recapitulate the histology of the primary tumors

• Published in: Pathology international 2013-02, Vol.63 (2), p.94-101
• Main Authors: Nishijima, Nobuhiko, Ishii, Genichiro, Nagai, Kanji, Atsumi, Naho, Aokage, Keiju, Tokunaga, Yuichi, Ichinokawa, Hideomi, Ohe, Yuichiro, Ochiai, Atsushi
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; cancer initiating cell; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; CD44; Female; Humans; Immunohistochemistry; lung cancer; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lymphatic Metastasis - pathology; Male; Membrane Glycoproteins - analysis; Middle Aged; Neoplastic Stem Cells; p63; podoplanin; squamous cell carcinoma; Tissue Array Analysis
• ISSN: 1320-5463; 1440-1827
• DOI: 10.1111/pin.12039

Cancer‐initiating cell (CIC) hypothesis suggests that CICs may be responsible for the generation of tumors that recapitulate the histology of the primary tumor at distant sites. We investigated the distribution of CIC markers (podoplanin (PDPN), CD44, and p63) positive cells of lung squamous cell carcinoma (SqCC) within primary and matched lymph node (LN) metastatic tumors to confirm this hypothesis (n = 113). In 61 cases, the PDPN‐positive cells were localized in more peripheral areas of the tumor nests than the CD44‐ and p63‐positive cells. This distribution pattern corresponded to a ‘hierarchical distribution (HD)’ reported previously. Among the cases with HD‐(+) primary tumors (n = 61), the number showing HD‐(+) LN metastatic tumors was 31 (51%), while among the cases with HD‐(−) primary tumors (n = 52), the number showing HD‐(+) LN metastatic tumors was 7 (13%) (p