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One of the strongest prognostic indicators of outcome is grade groups based on the Gleason grading system. Gleason grade 4 prostate cancer with cribriform morphology is associated with adverse outcomes and can be utilized clinically to improve risk stratification. The underpinnings of disease aggressiveness associated with cribriform architecture are not fully understood. Most studies have focused on genetic and molecular alterations in cribriform tumor cells; however, less is known about the tumor microenvironment in cribriform prostate cancer. Cancer\u2010associated fibroblasts (CAFs) are a heterogeneous population of fibroblasts in the tumor microenvironment that impact cancer aggressiveness. The overall goal of this study was to determine if cribriform prostate cancers are associated with a unique repertoire of CAFs. Radical prostatectomy whole\u2010tissue sections were analyzed for the expression of fibroblast markers (<jats:italic>ASPN<\/jats:italic> in combination with <jats:italic>FAP<\/jats:italic>, <jats:italic>THY1<\/jats:italic>, <jats:italic>ENG<\/jats:italic>, <jats:italic>NT5E<\/jats:italic>, <jats:italic>TNC<\/jats:italic>, and <jats:italic>PDGFR\u03b2<\/jats:italic>) in stroma adjacent to benign glands and in Gleason grade 3, Gleason grade 4 cribriform, and Gleason grade 4 noncribriform prostate cancer by RNAscope\u00ae. Halo\u00ae Software was used to quantify percent positive stromal cells and expression per positive cell. The fibroblast subtypes enriched in prostate cancer were highly heterogeneous. Both overlapping and distinct populations of low abundant fibroblast subtypes in benign prostate stroma were enriched in Gleason grade 4 prostate cancer with cribriform morphology compared to Gleason grade 4 prostate cancer with noncribriform morphology and Gleason grade 3 prostate cancer. In addition, gene expression was distinctly altered in CAF subtypes adjacent to cribriform prostate cancer. Overall, these studies suggest that cribriform prostate cancer has a unique tumor microenvironment that may distinguish it from other Gleason grade 4 morphologies and lower Gleason grades.<\/jats:p>","DOI":"10.1002\/cjp2.205","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T15:30:03Z","timestamp":1613835003000},"page":"271-286","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A distinct repertoire of <scp>cancer\u2010associated<\/scp> fibroblasts is enriched in cribriform prostate cancer"],"prefix":"10.1002","volume":"7","author":[{"given":"Amanda B","family":"Hesterberg","sequence":"first","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda L","family":"Rios","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University 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