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

Diagn Pathol. 2013 Nov 13:8:187. doi: 10.1186/1746-1596-8-187.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aberrant Crypt Foci / chemistry*
  • Aberrant Crypt Foci / pathology
  • Adenoma / chemistry*
  • Adenoma / pathology
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Colonic Neoplasms / chemistry*
  • Colonic Neoplasms / pathology
  • Colonic Polyps / chemistry*
  • Colonic Polyps / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Lithostathine / analysis*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Lithostathine
  • REG1A protein, human