ABSTRACT
Loss of stromal Caveolin-1 (CAV1) expression is associated with poor prognosis in various cancers. We evaluated the prognostic value of CAV1 expression of both cancer cells and stromal cells in colorectal liver metastases (CRLM) in patients undergoing hepatectomy. In this retrospective study, 109 patients were enrolled. CAV1 expression was studied by immunohistochemistry. The staining was scored semiquantitatively as weak or strong. Disease-free survival (DFS) and overall survival (OS) were calculated using both Kaplan-Meier and multivariate Coxregression methods. Weak stromal CAV1 expression was associated with decreased DFS and OS in univariate and in multivariate analysis (HR 2.00; 95% CI, 1.24-3.22; P = 0.004, and HR 2.47; 95% CI, 1.28-4.76; P = 0.007, respectively). Cancer cell CAV1 expression was not associated with DFS and OS. Five-year DFS and OS rates were 13% and 43%, respectively, in patients with weak stromal CAV1 expression and 40% and 71%, respectively, in patients with strong stromal CAV1 expression. In this study, we indicate that weak stromal CAV1 expression in CRLM is an adverse prognostic factor in patients who undergo liver resection for liver-only colorectal metastases. We suggest validation of this finding in an independent cohort and consideration of risk stratification for post-hepatectomy adjuvant follow-up and therapy.
Subject(s)
Caveolin 1/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Stromal Cells/metabolism , Aged , Aged, 80 and over , Biomarkers , Caveolin 1/metabolism , Female , Hepatectomy , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Magnetic Resonance Imaging/methods , Male , Middle Aged , PrognosisABSTRACT
PURPOSE: ß-catenin and AXIN2 play an important role in the Wnt signaling pathway. The aim of this study was to investigate ß-catenin and AXIN2 expression in colorectal cancer (CRC) and relate these findings with patients' clinicopathological features and prognosis. METHODS: 57 consecutive patients with surgically treated CRC were included in this study. Quantitative PCR and immunohistochemistry (IHC) analyses were performed to characterize the expression of the aforementioned markers in CRC tissues. RESULTS: ß-catenin overexpression in the nucleus was associated with advanced N stage CRCs (p=0.04). Multivariate Cox regression analysis showed that ß-catenin overexpression is an independent prognostic factor for overall survival (OS). A positive correlation between ß-catenin location and AXIN2 mRNA was observed. CONCLUSIONS: Nuclear ß-catenin is a valuable prognostic factor. AXIN2 is a component of the "Destruction Complex" and also a Wnt target gene. However, the clinical importance of AXIN2 expression in CRC remains unclear.
