Open AccessUtilizing digital pathology to quantify stromal caveolin-1 expression in malignant and benign ovarian tumors: Associations with clinicopathological parameters and clinical outcomes
Author(s) -
Daryoush SaeedVafa,
Douglas C. Marchion,
Susan McCarthy,
Ardeshir Hakam,
Alexis S. Lopez,
Robert M. Wenham,
Sachin M. Apte,
DungTsa Chen,
Anthony M. Magliocco,
Johnathan M. Lancaster,
Brett M. Reid,
Jennifer B. Permuth
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0256615
Subject(s) - stromal cell , stroma , immunohistochemistry , serous fluid , pathology , metastasis , epithelium , biology , tissue microarray , cancer research , ovarian cancer , tumor microenvironment , biomarker , tumor progression , cancer , medicine , biochemistry
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 ( r 2 = 0.69, p = 0.006) whereas there was no correlation for epithelial expression ( r 2 = 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.