Overexpression of regenerating gene Iα appears to reflect aberration of crypt cell compartmentalization in sessile serrated adenoma/polyps of the colon.
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.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7240956081100040.
Kentaro
K
Okamoto
Takahiro
T
Fujimori
Takeshi
T
Yamaguchi
Kazuhito
K
Ichikawa
Shigeki
S
Tomita
Tamotsu
T
Sugai
Johji
J
Imura
Yasuo
Y
Ohkura
Takashi
T
Yao
Shigehiko
S
Fujii
Toshihiro
T
Kusaka
Akira
A
Sekikawa
Hirokazu
H
Fukui
Tsutomu
T
Chiba
Hiroyuki
H
Kato
Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi 321-0293, Japan. hmitomi@dokkyomed.ac.jp.
Hiroyuki
H
Mitomi
D058739:Aberrant Crypt Foci / Q000737:chemistry* / Q000473:pathology; D000236:Adenoma / Q000737:chemistry* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000473:pathology; D003111:Colonic Polyps / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D051847:Lithostathine / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D051847:Lithostathine; C497617:REG1A protein, human