Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2015; 21(9): 2700-2710
Published online Mar 7, 2015. doi: 10.3748/wjg.v21.i9.2700
Mucinous phenotype and CD10 expression of primary adenocarcinoma of the small intestine
Reiko Kumagai, Kenichi Kohashi, Shunsuke Takahashi, Hidetaka Yamamoto, Minako Hirahashi, Kenichi Taguchi, Kenichi Nishiyama, Yoshinao Oda
Reiko Kumagai, Kenichi Kohashi, Shunsuke Takahashi, Hidetaka Yamamoto, Minako Hirahashi, Yoshinao Oda, Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Kenichi Taguchi, Department of Pathology, National Hospital Organization Kyushu Cancer Center, Fukuoka 811-1395, Japan
Kenichi Nishiyama, Division of Pathology, Japanese Red Cross Fukuoka Hospital, Fukuoka 815-8555, Japan
Author contributions: Kumagai R and Kohashi K performed the experiments, and the statistical analysis and drafted the manuscript; Kumagai R and Takahashi S carried out the experiments and analyzed the data; Kumagai R and Nishiyama K collected the data; Yamamoto H gave technical support and conceptual advice; Hirahashi M, Taguchi K and Oda Y participated in the design of the study and helped to draft the manuscript.
Ethics approval: The study was reviewed and approved by the Institutional Review Board of Kyushu University (IRB#25-191).
Informed consent: Informed consent was not obtained, but this study is not an interventional study and we completely anonymized or omitted all the information that might disclose the identity of the subjects.
Conflict-of-interest: The authors declare that there are no conflicts of interest to disclose.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Yoshinao Oda, Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. oda@surgpath.med.kyushu-u.ac.jp
Telephone: +81-92-6426061 Fax: +81-92-6425968
Received: October 11, 2014
Peer-review started: October 13, 2014
First decision: October 29, 2014
Revised: November 13, 2014
Accepted: December 20, 2014
Article in press: December 22, 2014
Published online: March 7, 2015
Processing time: 148 Days and 19.1 Hours
Abstract

AIM: To clarify the correlation with phenotypic expression, clinicopathological features, genetic alteration and microsatellite-instability status in small intestinal adenocarcinoma (SIA).

METHODS: The cases of 47 patients diagnosed with primary SIAs that were surgically resected at our institution in 1975-2005 were studied. We reviewed clinicopathological findings (age, gender, tumor size, gross appearance, histological morphologic type, invasion depth, lymphatic permeation, venous invasion, and lymph node metastasis), and the immunohistochemical expression of MUC5AC, MUC6, MUC2, CD10, and mismatch-repair (MMR) proteins (MLH1 and MSH2). We analyzed KRAS and BRAF gene mutations, and the microsatellite instability (MSI) status. The immunohistochemical staining of CD10, MUC2, MUC5AC and MUC6 was considered positive when distinct staining in > 5% of the adenocarcinoma cells was recorded. To evaluate of MMR protein expression, we used adjacent normal tissue including lymphoid follicles, inflammatory cells, and stromal cells as an internal positive control. Sections without nuclear staining in the tumor cells were considered to have lost the expression of the respective MMR protein.

RESULTS: There were 29 males and 18 females patients (mean age 59.9 years, range: 23-87 years). Tumors were located in the duodenum in 14 cases (30%), the jejunum in 21 cases (45%), and the ileum in 12 cases (25%). A phenotypic expression analysis revealed 20 MUC2-positive tumors (42.6%), 11 MUC5AC-positive (23.4%), 4 MUC6-positive (8.5%), and 7 CD10-positive (14.9%). The tumor sizes of the MUC2(+) tumors were significantly larger than those of the MUC2(-) tumors (mean, 5.7 ± 1.4 cm vs 4.7 ± 2.1 cm, P < 0.05). All three tumors with adenomatous component were positive for MUC2 (P < 0.05). Polypoid appearance was seen significantly more frequently in the CD10(+) group than in the CD10(-) group (P < 0.05). The tumor size was significantly larger in the CD10 (+) group than in the CD10(-) group (mean, 5.9 ± 1.4 cm vs 5.0 ± 2.1 cm, P < 0.05). Of 34 SIAs with successfully obtained MSI data, 4 were MSI-high. Of the 4 SIAs positive for both MUC5AC and MUC2, 3 showed MSI-H (75%) and 3 were mucinous adenocarcinoma (75%). KRAS mutations were detected in 4 SIAs. SIAs had KRAS mutation expressed only MUC2, but were negative for MUC5AC, MUC6 and CD10.

CONCLUSION: These findings suggest that the phenotypic expression of SIAs is correlated with their biological behavior, genetic alteration, and MSI status.

Keywords: Small intestine; Adenocarcinoma; Mucin; CD10; Microsatellite instability

Core tip: This study analyzed the immunohistochemical expression of mucin core proteins (MUC5AC, MUC6 and MUC2), CD10 and mismatch-repair proteins (MLH1, MSH2), microsatellite instability (MSI), and the mutational status of KRAS and BRAF in 47 primary small intestinal adenocarcinoma. We suggest that the mucin phenotype and CD10 expression of small intestinal adenocarcinoma correlates with biological behavior, genetic alteration, and MSI status. Notably, the preservation of CD10 expression may be correlated with favorable biological behavior. The SIA with co-expression of MUC5AC and MUC2 was correlated with MSI-H status and mucinous adenocarcinoma, similar to colorectal carcinoma.