Get access

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

Authors

  • Nobuhiko Nishijima,

    1. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    2. Thoracic Oncology Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    Search for more papers by this author
  • Genichiro Ishii,

    Corresponding author
    • Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    Search for more papers by this author
  • Kanji Nagai,

    1. Thoracic Oncology Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    Search for more papers by this author
  • Naho Atsumi,

    1. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    Search for more papers by this author
  • Keiju Aokage,

    1. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    2. Thoracic Oncology Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    Search for more papers by this author
  • Yuichi Tokunaga,

    1. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    2. Thoracic Oncology Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    Search for more papers by this author
  • Hideomi Ichinokawa,

    1. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    2. Thoracic Oncology Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    Search for more papers by this author
  • Yuichiro Ohe,

    1. Thoracic Oncology Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    Search for more papers by this author
  • Atsushi Ochiai

    Corresponding author
    • Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    Search for more papers by this author

Correspondence: Genichiro Ishii, MD, PhD, Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277-0882, Japan. Email: gishii@east.ncc.go.jp

Atsushi Ochiai, MD, PhD, Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277-0882, Japan. Email: aochiai@east.ncc.go.jp

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.

Ancillary