Podoplanin-Positive Cancer-Associated Fibroblasts Could Have Prognostic Value Independent of Cancer Cell Phenotype in Stage I Lung Squamous Cell Carcinoma Usefulness of Combining Analysis of Both Cancer Cell Phenotype and Cancer-Associated Fibroblast Phenotype

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), CD 10, and CD44 in the cancer cells and those of podoplanin, CA-IX, CD 10, 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 = .013 and P = .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. CHEST 2013; 143(4):963-970