title: Immunophenotypic features of metastatic lymph node tumors to predict recurrence in N2 lung squamous cell carcinoma.
abstract: Patients with mediastinal lymph node metastasis (N2) in squamous cell carcinoma (SqCC) of the lung have poor prognosis after surgical resection of the primary tumor. The aim of this study was to clarify predictive factors of the recurrence of pathological lung SqCC with N2 focusing on the biological characteristics of both cancer cells and cancer-associated fibroblasts (CAFs) in primary and metastatic lymph node tumors. We selected 64 patients with pathological primary lung N2 SqCC who underwent surgical complete resection and investigated the expressions of four epithelial-mesenchymal transition-related markers (caveolin, clusterin, E-cadherin, ZEB2), three cancer stem cell-related markers (ALDH-1, CD44 variant6, podoplanin) of cancer cells, and four markers of CAFs (caveolin, CD90, clusterin, podoplanin) in both primary and matched metastatic lymph node tumors in the N2 area. In the primary tumors, the expressions of all the examined molecules were not related to recurrence. However, in the metastatic lymph node tumors, high clusterin and ZEB2 expressions in the cancer cells and high podoplanin expression in the CAFs were significantly correlated with recurrence (P = 0.03, 0.04, and 0.007, respectively). In a multivariate analysis, only podoplanin expression in the CAFs in metastatic lymph node tumors was identified as a significantly independent predictive factor of recurrence (P = 0.03). Our study indicated that the immunophenotypes of both cancer cells and CAFs in metastatic lymph node tumors, but not primary tumors, provide useful information for predicting the recurrence of pathological N2 lung SqCC.
authors.affiliation: Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan; Division of Thoracic Surgery, Kyorin University, Tokyo, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Matsuwaki
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Zenke
authors.forename: Shinya
authors.initials: S
authors.lastname: Neri
authors.forename: Keiju
authors.initials: K
authors.lastname: Aokage
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hishida
authors.forename: Junji
authors.initials: J
authors.lastname: Yoshida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kondo
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Goya
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D051152:Clusterin / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D012097:Repressor Proteins / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism; D059016:Tumor Microenvironment; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D014408:Biomarkers, Tumor; C495242:CLU protein, human; D051152:Clusterin; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D018800:Thy-1 Antigens; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2
keywords: Cancer-associated fibroblasts; lung squamous cell carcinoma; metastatic lymph node tumors; recurrence; tumor microenvironment