Aberrant expressions of c-KIT and DOG-1 in mucinous and nonmucinous colorectal carcinomas and relation to clinicopathologic features and prognosis

Ann Diagn Pathol. 2015 Oct;19(5):335-40. doi: 10.1016/j.anndiagpath.2015.06.009. Epub 2015 Jul 11.

Abstract

c-KIT and DOG-1 are 2 highly expressed proteins in gastrointestinal stromal tumors. Few studies had investigated c-KIT, but not DOG-1, expression in colorectal carcinoma (CRC). This study aims to investigate expressions of c-KIT and DOG-1 in colorectal mucinous carcinoma and nonmucinous carcinoma using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique, and immunohistochemistry for c-KIT and DOG-1 was done. We found that aberrant c-KIT expression was detected in 12 cases (8%); 6 cases (4%) showed strong expression. Aberrant DOG-1 expression was detected in 15 cases (10%); among them, only 4 cases (2.7%) showed strong expression. Nonmucinous adenocarcinoma showed a significantly high expression of c-KIT, but not DOG-1, than MA. Aberrant c-KIT and DOG-1 expressions were significantly unrelated but were associated with excessive microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. In conclusion, aberrant c-KIT and DOG-1 expressions in CRC are rare events, either in NMA or MA. Nonmucinous adenocarcinoma showed a significantly higher expression of c-KIT, but not DOG-1, than MA. The expressions of both in CRC are significantly unrelated but are associated with microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. So, c-KIT and DOG-1 immunostaining is not a cost-effective method of identifying patients with CRC who may benefit from treatment with tyrosine kinase inhibitors.

Keywords: Colorectal; DOG-1; Mucinous; c-KIT.

MeSH terms

  • Adenocarcinoma, Mucinous / metabolism*
  • Adult
  • Anoctamin-1
  • Biomarkers, Tumor / biosynthesis
  • Chloride Channels / biosynthesis*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Prognosis
  • Proto-Oncogene Proteins c-kit / biosynthesis*
  • Retrospective Studies
  • Stem Cell Factor / metabolism
  • Tissue Array Analysis

Substances

  • ANO1 protein, human
  • Anoctamin-1
  • Biomarkers, Tumor
  • Chloride Channels
  • Neoplasm Proteins
  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit