Utilizing digital pathology to quantify stromal caveolin-1 expression in malignant and benign ovarian tumors: Associations with clinicopathological parameters and clinical outcomes.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Caveolin 1/*metabolism ; Cystadenocarcinoma, Serous/*metabolism ; Ovarian Neoplasms/*metabolism ; Ovary/*metabolism ; Stromal Cells/*metabolism; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Cystadenocarcinoma, Serous/mortality ; Cystadenocarcinoma, Serous/pathology ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms/mortality ; Ovarian Neoplasms/pathology ; Ovary/pathology ; Stromal Cells/pathology ; Survival Rate ; Tissue Array Analysis

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.
Competing Interests: Dr. Robert Wenham reports grants and personal fees from Merck, personal fees from Tesaro/GSK, personal fees from Genentech, personal fees from Legend Biotech, personal fees from AbbVie, personal fees from Astrazeneca, grants and personal fees from Ovation Diagnostics, personal fees from Clovis Oncology, personal fees from Regeneron, outside the submitted work. Dr. Johnathan Lancaster employed by Regeneron. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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P30 CA076292 United States CA NCI NIH HHS

0 (Biomarkers, Tumor)
0 (Caveolin 1)

Date Created: 20211123 Date Completed: 20211224 Latest Revision: 20211224

20221213

PMC8610269

10.1371/journal.pone.0256615

34813586