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

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 ovaria...

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Autores principales: Daryoush Saeed-Vafa, Douglas C Marchion, Susan M McCarthy, Ardeshir Hakam, Alexis Lopez, Robert M Wenham, Sachin M Apte, Dung-Tsa Chen, Anthony M Magliocco, Johnathan M Lancaster, Brett M Reid, Jennifer B Permuth
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:5ca8a7d61e0f4af186e6fa6b2b9a9a6f2021-12-02T20:16:15ZUtilizing digital pathology to quantify stromal caveolin-1 expression in malignant and benign ovarian tumors: Associations with clinicopathological parameters and clinical outcomes.1932-620310.1371/journal.pone.0256615https://doaj.org/article/5ca8a7d61e0f4af186e6fa6b2b9a9a6f2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256615https://doaj.org/toc/1932-6203Loss 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.Daryoush Saeed-VafaDouglas C MarchionSusan M McCarthyArdeshir HakamAlexis LopezRobert M WenhamSachin M ApteDung-Tsa ChenAnthony M MaglioccoJohnathan M LancasterBrett M ReidJennifer B PermuthPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0256615 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Daryoush Saeed-Vafa
Douglas C Marchion
Susan M McCarthy
Ardeshir Hakam
Alexis Lopez
Robert M Wenham
Sachin M Apte
Dung-Tsa Chen
Anthony M Magliocco
Johnathan M Lancaster
Brett M Reid
Jennifer B Permuth
Utilizing digital pathology to quantify stromal caveolin-1 expression in malignant and benign ovarian tumors: Associations with clinicopathological parameters and clinical outcomes.
description 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.
format article
author Daryoush Saeed-Vafa
Douglas C Marchion
Susan M McCarthy
Ardeshir Hakam
Alexis Lopez
Robert M Wenham
Sachin M Apte
Dung-Tsa Chen
Anthony M Magliocco
Johnathan M Lancaster
Brett M Reid
Jennifer B Permuth
author_facet Daryoush Saeed-Vafa
Douglas C Marchion
Susan M McCarthy
Ardeshir Hakam
Alexis Lopez
Robert M Wenham
Sachin M Apte
Dung-Tsa Chen
Anthony M Magliocco
Johnathan M Lancaster
Brett M Reid
Jennifer B Permuth
author_sort Daryoush Saeed-Vafa
title Utilizing digital pathology to quantify stromal caveolin-1 expression in malignant and benign ovarian tumors: Associations with clinicopathological parameters and clinical outcomes.
title_short Utilizing digital pathology to quantify stromal caveolin-1 expression in malignant and benign ovarian tumors: Associations with clinicopathological parameters and clinical outcomes.
title_full Utilizing digital pathology to quantify stromal caveolin-1 expression in malignant and benign ovarian tumors: Associations with clinicopathological parameters and clinical outcomes.
title_fullStr Utilizing digital pathology to quantify stromal caveolin-1 expression in malignant and benign ovarian tumors: Associations with clinicopathological parameters and clinical outcomes.
title_full_unstemmed Utilizing digital pathology to quantify stromal caveolin-1 expression in malignant and benign ovarian tumors: Associations with clinicopathological parameters and clinical outcomes.
title_sort 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 (PLoS)
publishDate 2021
url https://doaj.org/article/5ca8a7d61e0f4af186e6fa6b2b9a9a6f
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