Kei Shimizu1,2,3, Keisuke Kirita1, Keiju Aokage2, Motohiro Kojima1, Tomoyuki Hishida2, Takeshi Kuwata1, Satoshi Fujii1, Atsushi Ochiai1, Kazuhito Funai3, Junji Yoshida2, Masahiro Tsuboi2, Genichiro Ishii4. 1. Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 2. Division of Thoracic Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 3. First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, 431-3192, Japan. 4. Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. gishii@east.ncc.go.jp.
Abstract
PURPOSE: Caveolin is an essential constituent of caveolae and has many biological functions. Expression of caveolin-1 in cancer cells was reported to be a prognostic marker in several types of cancers, the prognostic significance of its expression in cancer-associated fibroblasts (CAFs) has not been investigated. This study aimed to evaluate the clinicopathological significance of expression by CAFs in lung adenocarcinoma. METHODS: We examined caveolin-1 expression in both CAFs and cancer cells in stage I invasive lung adenocarcinoma (n = 412) and analyzed the relationship between the expression and clinicopathological factors. RESULTS: Caveolin-1 expression by CAFs and cancer cells was observed in 12.1% and 7.8% of adenocarcinomas, respectively. Tumors with caveolin-1-positive CAFs had vascular and pleural invasion significantly more frequently than those with caveolin-1-negative CAF (p < 0.05). This was also the cases with tumors with caveolin-1-positive cancer cells (p < 0.01). Caveolin-1 expression by CAFs and that by cancer cells were significant predictors of shorter recurrence-free survival (p < 0.001). Caveolin-1 expression by CAFs and cancer cells was found in 25% and 30% of solid predominant subtype, respectively, but only 9.2% and 2.7% of non-solid predominant subtype, respectively. The frequency of cases with caveolin-1-positive CAFs or cancer cells was significantly higher in the solid predominant subtype than in non-solid predominant subtype (p < 0.001). CONCLUSIONS: Our current results highlight the prognostic importance of caveolin-1 expression by CAFs in stage I lung adenocarcinoma and provide new insights into the biological significance of caveolin-1 in the tumor microenvironment, especially in microenvironment of solid predominant adenocarcinoma.
PURPOSE:Caveolin is an essential constituent of caveolae and has many biological functions. Expression of caveolin-1 in cancer cells was reported to be a prognostic marker in several types of cancers, the prognostic significance of its expression in cancer-associated fibroblasts (CAFs) has not been investigated. This study aimed to evaluate the clinicopathological significance of expression by CAFs in lung adenocarcinoma. METHODS: We examined caveolin-1 expression in both CAFs and cancer cells in stage I invasive lung adenocarcinoma (n = 412) and analyzed the relationship between the expression and clinicopathological factors. RESULTS:Caveolin-1 expression by CAFs and cancer cells was observed in 12.1% and 7.8% of adenocarcinomas, respectively. Tumors with caveolin-1-positive CAFs had vascular and pleural invasion significantly more frequently than those with caveolin-1-negative CAF (p < 0.05). This was also the cases with tumors with caveolin-1-positive cancer cells (p < 0.01). Caveolin-1 expression by CAFs and that by cancer cells were significant predictors of shorter recurrence-free survival (p < 0.001). Caveolin-1 expression by CAFs and cancer cells was found in 25% and 30% of solid predominant subtype, respectively, but only 9.2% and 2.7% of non-solid predominant subtype, respectively. The frequency of cases with caveolin-1-positive CAFs or cancer cells was significantly higher in the solid predominant subtype than in non-solid predominant subtype (p < 0.001). CONCLUSIONS: Our current results highlight the prognostic importance of caveolin-1 expression by CAFs in stage I lung adenocarcinoma and provide new insights into the biological significance of caveolin-1 in the tumor microenvironment, especially in microenvironment of solid predominant adenocarcinoma.
Authors: N Oka; M Yamamoto; C Schwencke; J Kawabe; T Ebina; S Ohno; J Couet; M P Lisanti; Y Ishikawa Journal: J Biol Chem Date: 1997-12-26 Impact factor: 5.157
Authors: Jose A Karam; Yair Lotan; Claus G Roehrborn; Raheela Ashfaq; Pierre I Karakiewicz; Shahrokh F Shariat Journal: Prostate Date: 2007-05-01 Impact factor: 4.104