{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T13:09:38Z","timestamp":1770556178234,"version":"3.49.0"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T00:00:00Z","timestamp":1577145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["110972 and 70113213"],"award-info":[{"award-number":["110972 and 70113213"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The KrasG12D\/+;LSL-Trp53R172H\/+;Pdx-1-Cre (KPC) mouse model is frequently employed for preclinical therapeutic testing, in particular in regard to antistromal therapies. Here, we investigate the prognostic implications of histopathological features that may guide preclinical trial design. Pancreatic tumor tissue from n = 46 KPC mice was quantitatively analyzed using immunohistochemistry and co-immunofluorescence for proliferation (Ki67), mitotic rate (phospho-Histone 3, PHH3), apoptosis (cleaved caspase-3, CC3), collagen content, secreted protein acidic and rich in cysteine (SPARC), hyaluronic acid (HA), and \u03b1-smooth muscle actin (\u03b1-SMA). Furthermore, mean vessel density (MVD), mean lumen area (MLA), grading, activated stroma index (ASI), and fibroblast-proliferation rate (\u03b1-SMA\/Ki67) were assessed. Univariate analysis using the Kaplan\u2013Meier estimator and Cox regression model for continuous variables did not show association between survival and any of the analyzed parameters. Spearman correlation demonstrated that desmoplasia was inversely correlated with differentiated tumor grade (\u03c1 = \u22120.84). Ki67 and PHH3 synergized as proliferation markers (\u03c1 = 0.54), while SPARC expression was positively correlated with HA content (\u03c1 = 0.37). MVD and MLA were correlated with each other (\u03c1 = 0.31), while MLA positively correlated with CC3 (\u03c1 = 0.45). Additionally, increased MVD was correlated with increased fibroblast proliferation rate (\u03b1-SMA + Ki67; \u03c1 = 0.36). Our pilot study provides evidence that individual histopathological parameters of the primary tumor of KPC mice are not associated with survival, and may hint at the importance of systemic tumor-related effects such as cachexia.<\/jats:p>","DOI":"10.3390\/cells9010058","type":"journal-article","created":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T10:28:43Z","timestamp":1577183323000},"page":"58","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Stromal Features of the Primary Tumor Are Not Prognostic in Genetically Engineered Mice of Pancreatic Cancer"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9765-4075","authenticated-orcid":false,"given":"Marie C.","family":"Hasselluhn","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie S.","family":"Patzak","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f6ren M.","family":"Buchholz","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Str\u00f6bel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker","family":"Ellenrieder","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Maisonneuve","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Biostatistics, IEO Istituto Europeo di Oncologia IRCCS, P.I. 08691440153 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albrecht","family":"Neesse","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1002\/cam4.767","article-title":"Projections of cancer incidence and cancer-related deaths in Germany by 2020 and 2030","volume":"5","author":"Quante","year":"2016","journal-title":"Cancer Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1158\/0008-5472.CAN-14-0155","article-title":"Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States","volume":"74","author":"Rahib","year":"2014","journal-title":"Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1136\/gutjnl-2018-316451","article-title":"Stromal biology and therapy in pancreatic cancer: ready for clinical translation?","volume":"68","author":"Neesse","year":"2019","journal-title":"Gut"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1136\/gut.2010.226092","article-title":"Stromal biology and therapy in pancreatic cancer","volume":"60","author":"Neesse","year":"2011","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ccr.2007.01.012","article-title":"Chronic Pancreatitis Is Essential for Induction of Pancreatic Ductal Adenocarcinoma by K-Ras Oncogenes in Adult Mice","volume":"11","author":"Guerra","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1158\/2159-8290.CD-13-0593","article-title":"Inflammation-induced NFATc1-STAT3 transcription complex promotes pancreatic cancer initiation by KrasG12D","volume":"4","author":"Baumgart","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/path.5224","article-title":"Inter- and intra-tumoural heterogeneity in cancer-associated fibroblasts of human pancreatic ductal adenocarcinoma","volume":"248","author":"Neuzillet","year":"2018","journal-title":"J. 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