Open Access Research

Overexpression of regenerating gene Iα appears to reflect aberration of crypt cell compartmentalization in sessile serrated adenoma/polyps of the colon

Kentaro Okamoto12, Takahiro Fujimori1, Takeshi Yamaguchi12, Kazuhito Ichikawa1, Shigeki Tomita1, Tamotsu Sugai3, Johji Imura4, Yasuo Ohkura5, Takashi Yao6, Shigehiko Fujii7, Toshihiro Kusaka7, Akira Sekikawa8, Hirokazu Fukui9, Tsutomu Chiba10, Hiroyuki Kato2 and Hiroyuki Mitomi1*

Author Affiliations

1 Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi 321-0293, Japan

2 First Department of Surgery, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi 321-0293, Japan

3 Division of Molecular Diagnostic Pathology, Department of Pathology, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan

4 Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan

5 Department of Pathology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan

6 Department of Human Pathology, Juntendo University School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan

7 Department of Gastroenterology, Kyoto Katsura Hospital, 17 Yamada Hirao, Nishikyo-ku, Kyoto 615-8256, Japan

8 Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-30 Fudegasaki, Tennoji-ku, Osaka 543-8555, Japan

9 Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya, Hyogo 663-8501, Japan

10 Department of Gastroenterology and Hepatology, Kyoto, University Graduate School of Medicine, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan

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Diagnostic Pathology 2013, 8:187  doi:10.1186/1746-1596-8-187

Published: 13 November 2013

Abstract

Background

Colorectal sessile serrated adenoma/polyps (SSA/Ps) are characterized by asymmetrical distribution of Ki67-positive cells, which varies among crypts and involves the crypt length to a variable extent; the pattern has been designated as aberration of crypt cell compartmentalization. The regenerating gene (REG) Iα is a cell growth and/or anti-apoptotic factor and its overexpression might be associated with aberration of crypt cell compartmentalization in SSA/Ps. We investigated REG Iα expression in SSA/Ps in comparison to hyperplastic polyps (HPs).

Methods

A total of 64 cases of serrated polyps (≥10 mm in size), including 53 SSA/Ps and 11 HPs, were included in the present study. Immunostaining was performed using a labeled streptavidin-biotin method. REG Iα expression was classified as follows: (i) expression of endocrine cells: grade 0 (a few positive cells) to 3 (marked increase in positive cells); (ii) expression of goblet cells: grade 0 (negative) to 2 (positive for crypts and surface epithelial cells); (iii) staining intensity of goblet cells: grade 0 (negative) to 2 (strong); (iv) staining intensity of crypt (absorptive) cell membranes: grade 0 (negative) to 2 (strong). The presence of aberration of crypt cell compartmentalization was assessed using Ki67 immunostaining.

Results

With regard to the REG Iα expression of endocrine cells, 8 out of 11 HPs (73%) were grade 0, whereas 51 of 53 SSA/Ps (96%) were grade 1 or higher (p < 0.001). With regard to the distribution of REG Iα-immunoreactive goblet cells, 10 of 11 HPs (91%) were grade 1, whereas 50 of 53 SSA/Ps (94%) were grade 2 (p < 0.001). A similar trend was found in the staining intensity of goblet cells or crypt cell membranes (p = 0.011). Aberration of crypt cell compartmentalization was more frequently identified in SSA/Ps (72%) than in HPs (18%; p = 0.002). A significant association was observed between REG Iα overexpression and the aberration of crypt cell compartmentalization in serrated polyps (p = 0.037).

Conclusions

REG Iα overexpression is a characteristic of SSA/Ps, which appears to reflect aberration of crypt cell compartmentalization.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7240956081100040 webcite

Keywords:
Colon; Crypt cell compartmentalization; Hyperplastic polyp; REG Iα; Sessile serrated adenoma/polyp