Prognostic implication of SOX2 expression in small intestinal adenocarcinoma
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ORIGINAL ARTICLE
Prognostic implication of SOX2 expression in small intestinal adenocarcinoma Jeong Won Kim 1,2 & Joon-Yong Chung 1 & Kris Ylaya 1 & Yoonho Park 1 & Sun-Young Jun 3 & Seung-Mo Hong 4 & Stephen M. Hewitt 1 Received: 8 June 2020 / Revised: 23 September 2020 / Accepted: 5 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The presence of KRAS mutation enhances the stem cell features of colorectal carcinoma cells containing mutant adenomatous polyposis coli (APC). However, their potential role in small intestinal adenocarcinoma remains elusive. Here, we aimed to investigate the clinical significance of cancer stem cell markers expression in the context of small intestinal adenocarcinoma with the KRAS genotype. SOX2, NANOG, and OCT4 expression were assessed by immunohistochemistry and digital image analysis, and their potential association with KRAS was further examined in 185 Korean patients with small intestinal adenocarcinomas, which were collected from 22 institutions in South Korea. Positive expression of SOX2, NANOG, and OCT4 was detected in 65 (35.1%), 94 (50.8%), and 82 (44.3%) of patients, respectively. Patients with high SOX2 (SOX2+) expression displayed worse overall survival compared to those with low SOX2 (SOX2−) expression (P < 0.001). Patients with SOX2+/ mutant KRAS (KRASMT) (11.1 months) had significantly shorter overall survival than those with SOX2−/KRASWT (53.6 months) (P < 0.001). In multivariate analysis, SOX2+, distal location, high pT and pN categories, microsatellite stable, and absence of predisposing diseases were independent prognostic factors for worse overall survival. These results suggest that SOX2 expression has the potential to predict clinical outcomes in patients with small intestinal adenocarcinomas. Keywords Small intestine . Adenocarcinoma . Prognosis . Cancer stem cell . KRAS
Introduction Jeong Won Kim and Joon-Yong Chung contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00428-020-02946-x) contains supplementary material, which is available to authorized users. * Seung-Mo Hong [email protected] * Stephen M. Hewitt [email protected] 1
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
2
Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07441, Republic of Korea
3
Department of Pathology, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 21431, Republic of Korea
4
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05550, Republic of Korea
Small intestinal adenocarcinoma is a relatively rare malignancy, accounting for 1 to 3% of all gastrointestinal tumors [29, 32]. Small intestinal adenocarcinomas are most commonly found in the duodenum, followed by the jejunum and ileum [12]. Moreover, duodenal adenocarcinomas are often observed
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