Abstract
Loss of stromal caveolin-1 (Cav-1) is a biomarker of a cancer-associated fibroblast (CAF) phenotype and is related to progression, metastasis, and poor outcomes in several cancers. The objective of this study was to evaluate the clinical significance of Cav-1 expression in invasive epithelial ovarian cancer (OvCa). Epithelial and stromal Cav-1 expression were quantified in serous OvCa and benign ovarian tissue in two, independent cohorts–one quantified expression using immunohistochemistry (IHC) and the other using multiplex immunofluorescence (IF) with digital image analysis designed to target CAF-specific expression. Cav-1 expression was significantly downregulated in OvCa stroma compared to non-neoplastic stroma using both the IHC (p = 0.002) and IF (p = 1.8x10-13) assays. OvCa stroma showed Cav-1 downregulation compared to tumor epithelium with IHC (p = 1.2x10-24). Conversely, Cav-1 expression was higher in OvCa stroma compared to tumor epithelium with IF (p = 0.002). There was moderate correlation between IHC and IF methods for stromal Cav-1 expression (r2 = 0.69, p = 0.006) whereas there was no correlation for epithelial expression (r2 = 0.006, p = 0.98). Irrespective of the staining assay, neither response to therapy or overall survival correlated with the expression level of Cav-1 in the stroma or tumor epithelium. Our findings demonstrate a loss of stromal Cav-1 expression in ovarian serous carcinomas. Studies are needed to replicate these findings and explore therapeutic implications, particularly for immunotherapy response.
Highlights
Ovarian carcinoma (OvCa) is the fifth leading cause of cancer-related deaths among women in the United States
Since OvCa incidence and mortality is highest in non-hispanic whites1 and most OvCas are of the serous subtype, which is etiologically distinct from other histologies [28], our analyses focused on invasive serous adenocarcinomas among non-Hispanic whites
Given the emerging importance of the tumor microenvironment with respect to carcinogenesis and chemoresistance, we evaluated the expression of Cav-1, a key potential regulator, exploring its role in ovarian serous adenocarcinoma as a therapeutic and prognostic factor
Summary
Ovarian carcinoma (OvCa) is the fifth leading cause of cancer-related deaths among women in the United States. In 2020, an estimated 21,750 new cases of OvCa and 13,940 related deaths occurred, making it the most deadly of all gynecologic cancers [1]. Cancer-associated fibroblasts (CAFs) are the most abundant cells in the tumor microenvironment and are known to promote tumor growth, invasion, and metastasis [8,9,10,11,12] and impact the efficacy of chemotherapy [8, 10,11,12,13]. Ovarian CAFs are genetically more stable than tumor cells [14], making them less prone to developing chemoresistance and excellent therapeutic targets. The clinical significance of proteins associated with CAFs in OvCa is largely unexplored
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