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.
Highlights
The treatment of colorectal liver metastases (CRLM) by surgical resection has become accepted and its use has increased over the last two decades
A total of 139 patients were identified from the institutional database; 109 patients were eligible for inclusion in the study
43% of the patients had solitary liver metastases, while metastases were synchronous in 70% of patients
Summary
The treatment of colorectal liver metastases (CRLM) by surgical resection has become accepted and its use has increased over the last two decades. In an attempt to individualise perioperative systemic therapy, prognostic factors have been sought to classify hepatectomy patients at low and increased risk of disease recurrence[3,4,5]. The prognostic significance of a variety of stromal biomarkers in cancer patients has been demonstrated[7]. Loss of stromal CAV1 expression has been characterised as a key regulator in the development of the “reverse Warburg effect” and “the autophagic tumour stroma model of cancer metabolism”[13,14,15]. CAFs with loss of CAV1 expression have an increased ability to provide nutrients to cancer cells, and in this fashion, promote aggressive tumour growth[13,14,15]
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