title: Cancer-initiating cell marker-positive cells generate metastatic tumors that recapitulate the histology of the primary tumors.
abstract: 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 < 0.01). Primary and matched pulmonary metastatic (PM) tumors were also analyzed (n = 31), and a significant relationship of the HD pattern between them was also detected (p = 0.01). These results indicate that PDPN-positive cells might reflect the most immature cells in the differentiation process of metastatic SqCC and might generate metastatic tumors that recapitulate the histologic heterogeneity of the primary tumor.
authors: Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors: Nobuhiko
authors: N
authors: Nishijima
authors: Genichiro
authors: G
authors: Ishii
authors: Kanji
authors: K
authors: Nagai
authors: Naho
authors: N
authors: Atsumi
authors: Keiju
authors: K
authors: Aokage
authors: Yuichi
authors: Y
authors: Tokunaga
authors: Hideomi
authors: H
authors: Ichinokawa
authors: Yuichiro
authors: Y
authors: Ohe
authors: Atsushi
authors: A
authors: Ochiai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D014411:Neoplastic Stem Cells; D046888:Tissue Array Analysis; D000098853:Podoplanin
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin