BACKGROUND: Most pancreatic ductal adenocarcinomas (PDACs) metastasize even after curative resection. Our goal was to investigate the important factors affecting metastasis and overall survival (OS). METHODS: We studied 88 PDACs with R0 resection and evaluated immunohistochemical markers on tissue microarrays to assess the expression levels of the following: EGFR, amphiregulin, VEGF, p-c-met, MMP2, MMP7, MMP9, CXCR3, and CXCR4. RESULTS: The median OS in patients who had positive versus negative expression of AREG and MMP9 were 25 versus 16 months and 24 versus 13 months, respectively (P = 0.03, P = 0.006). However, the median OS in patients with positive versus negative expression of MMP2 was 22 versus 37 months (P = 0.04). Immunoprofiles also revealed that patients with positive expression of p-c-met or VEGF had significantly shorter distant metastasis-free survival. Adjuvant treatment, postoperative decrease of CA 19-9, angiolymphatic invasion, AREG, and MMP2 were independent prognostic factors affecting OS in multivariate analysis. CONCLUSIONS: Immunoprofiles revealed the groups with unfavorable tumor biology: negative expression of AREG and positive expression of MMP2. Also, high immunoreactivity of p-c-met or VEGF seemed to be associated with early distant organ metastasis in R0 resected PDACs; however, they still need to be further investigated. These results may give us useful insights in understanding the tumor biology and the patterns of PDAC dissemination.
BACKGROUND: Most pancreatic ductal adenocarcinomas (PDACs) metastasize even after curative resection. Our goal was to investigate the important factors affecting metastasis and overall survival (OS). METHODS: We studied 88 PDACs with R0 resection and evaluated immunohistochemical markers on tissue microarrays to assess the expression levels of the following: EGFR, amphiregulin, VEGF, p-c-met, MMP2, MMP7, MMP9, CXCR3, and CXCR4. RESULTS: The median OS in patients who had positive versus negative expression of AREG and MMP9 were 25 versus 16 months and 24 versus 13 months, respectively (P = 0.03, P = 0.006). However, the median OS in patients with positive versus negative expression of MMP2 was 22 versus 37 months (P = 0.04). Immunoprofiles also revealed that patients with positive expression of p-c-met or VEGF had significantly shorter distant metastasis-free survival. Adjuvant treatment, postoperative decrease of CA 19-9, angiolymphatic invasion, AREG, and MMP2 were independent prognostic factors affecting OS in multivariate analysis. CONCLUSIONS: Immunoprofiles revealed the groups with unfavorable tumor biology: negative expression of AREG and positive expression of MMP2. Also, high immunoreactivity of p-c-met or VEGF seemed to be associated with early distant organ metastasis in R0 resected PDACs; however, they still need to be further investigated. These results may give us useful insights in understanding the tumor biology and the patterns of PDAC dissemination.
Authors: Wilson Petrushnko; Justin S Gundara; Philip R De Reuver; Greg O'Grady; Jaswinder S Samra; Anubhav Mittal Journal: HPB (Oxford) Date: 2016-07-14 Impact factor: 3.647
Authors: Franziska Brandes; Katharina Schmidt; Christine Wagner; Julia Redekopf; Hans Jürgen Schlitt; Edward Kenneth Geissler; Sven Arke Lang Journal: BMC Cancer Date: 2015-02-19 Impact factor: 4.430
Authors: Srinivasa P Pothula; Zhihong Xu; David Goldstein; Romano C Pirola; Jeremy S Wilson; Minoti V Apte Journal: Int J Mol Sci Date: 2020-12-01 Impact factor: 5.923
Authors: Kaidi Mikhitarian; Maressa Pollen; Zhiguo Zhao; Yu Shyr; Nipun B Merchant; Alexander Parikh; Frank Revetta; M Kay Washington; Cindy Vnencak-Jones; Chanjuan Shi Journal: Mod Pathol Date: 2013-11-01 Impact factor: 7.842