Utilizing Digital Pathology to Quantify Stromal Caveolin-1 Expression in Malignant and Benign Ovarian Tumors: Associations with Clinicopathological Parameters and Clinical Outcomes

Saeed-Vafa, D.; Marchion, D. C.; McCarthy, S. M.; Hakam, A.; Lopez, A.; Wenham, R. M.; Apte, S. M.; Chen, D.-T.; Magliocco, A. M.; Lancaster, J. M.; Reid, B. M.; Permuth, J. B.

doi:10.1101/2021.08.18.456818

bioRxiv · 10.1101/2021.08.18.456818

Utilizing Digital Pathology to Quantify Stromal Caveolin-1 Expression in Malignant and Benign Ovarian Tumors: Associations with Clinicopathological Parameters and Clinical Outcomes

Saeed-Vafa, D.·Marchion, D. C.·McCarthy, S. M.·Hakam, A.·Lopez, A.·Wenham, R. M.·Apte, S. M.·Chen, D.-T.·Magliocco, A. M.·Lancaster, J. M.·Reid, B. M.·Permuth, J. B.

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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.

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Saeed-Vafa, D., Marchion, D. C., McCarthy, S. M., Hakam, A., Lopez, A., Wenham, R. M., Apte, S. M., Chen, D.-T., Magliocco, A. M., Lancaster, J. M., Reid, B. M., Permuth, J. B.. 2021-08-18. Utilizing Digital Pathology to Quantify Stromal Caveolin-1 Expression in Malignant and Benign Ovarian Tumors: Associations with Clinicopathological Parameters and Clinical Outcomes. https://doi.org/10.1101/2021.08.18.456818

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