Shotaro Ono1, Genichiro Ishii2, Kanji Nagai3, Teruhisa Takuwa4, Junji Yoshida3, Mitsuyo Nishimura3, Tomoyuki Hishida3, Keiju Aokage3, Satoshi Fujii5, Norihiko Ikeda6, Atsushi Ochiai5. 1. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba; Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba; Departments of Thoracic Surgery, Tokyo Medical University, Shinjuku, Tokyo, Japan. 2. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba. Electronic address: gishii@east.ncc.go.jp. 3. Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba. 4. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba; Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba. 5. Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba. 6. Departments of Thoracic Surgery, Tokyo Medical University, Shinjuku, Tokyo, Japan.
Abstract
BACKGROUND: The prognostic significance of the tumor microenvironment, which is created by both cancer cells and cancer-associated fibroblasts (CAFs), has been increasingly recognized. The purpose of this study was to analyze the prognostic markers of stage I squamous cell carcinoma (SqCC), with special reference to the immunophenotypes of both cancer cells and CAFs. METHODS: A total of 142 patients with stage I SqCC were included in this study. We examined the expressions of E-cadherin, laminin-5, podoplanin, c-MET, carbonic anhydrase IX (CA-IX), CD10, and CD44 in the cancer cells and those of podoplanin, CA-IX, CD10, and CD44 in the CAFs to evaluate their prognostic value. RESULTS: Patients with low E-cadherin expression in the cancer cells showed a significantly poorer prognosis than those with high E-cadherin expression in the cancer cells ( P , .001). On the other hand, high podoplanin expression in the CAFs was also associated with a significantly poorer prognosis ( P , .001). A multivariate analysis identified low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs as significantly independent prognostic factors for overall survival ( P 5 .013 and P 5 .0011, respectively). According to subgroup analyses combining E-cadherin expression in cancer cells and podoplanin expression in CAFs, 5-year overall survival of patients with low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs was 7.0% and showed a significantly poorer prognosis as compared with other groups ( P , .001). CONCLUSIONS: The current study indicates that immunophenotypes of CAFs could have a prognostic value independent of those of the cancer cells in SqCC.
BACKGROUND: The prognostic significance of the tumor microenvironment, which is created by both cancer cells and cancer-associated fibroblasts (CAFs), has been increasingly recognized. The purpose of this study was to analyze the prognostic markers of stage I squamous cell carcinoma (SqCC), with special reference to the immunophenotypes of both cancer cells and CAFs. METHODS: A total of 142 patients with stage I SqCC were included in this study. We examined the expressions of E-cadherin, laminin-5, podoplanin, c-MET, carbonic anhydrase IX (CA-IX), CD10, and CD44 in the cancer cells and those of podoplanin, CA-IX, CD10, and CD44 in the CAFs to evaluate their prognostic value. RESULTS:Patients with low E-cadherin expression in the cancer cells showed a significantly poorer prognosis than those with high E-cadherin expression in the cancer cells ( P , .001). On the other hand, high podoplanin expression in the CAFs was also associated with a significantly poorer prognosis ( P , .001). A multivariate analysis identified low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs as significantly independent prognostic factors for overall survival ( P 5 .013 and P 5 .0011, respectively). According to subgroup analyses combining E-cadherin expression in cancer cells and podoplanin expression in CAFs, 5-year overall survival of patients with low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs was 7.0% and showed a significantly poorer prognosis as compared with other groups ( P , .001). CONCLUSIONS: The current study indicates that immunophenotypes of CAFs could have a prognostic value independent of those of the cancer cells in SqCC.
Authors: Kyuichi Kadota; Daniel Buitrago; Ming-Ching Lee; Jonathan Villena-Vargas; Camelia S Sima; David R Jones; William D Travis; Prasad S Adusumilli Journal: Lung Cancer Date: 2015-06-15 Impact factor: 5.705