High expression of atypical protein kinase C lambda/iota in gastric cancer as a prognostic factor for recurrence

Ann Surg Oncol. 2010 Jan;17(1):81-8. doi: 10.1245/s10434-009-0708-x. Epub 2009 Sep 23.

Abstract

Background: The atypical protein kinase C lambda/iota (aPKClambda/iota) is involved in several signal transduction pathways that influence cell growth, apoptosis, and the establishment and maintenance of epithelial cell polarity. Overexpression of aPKClambda/iota has been reported in several cancers and been shown to be associated with oncogenesis. However, the expression and role of aPKClambda/iota in gastric cancer, one of the commonest cancers in Asia, have not so far been investigated. This study aimed to clarify the relationship between aPKClambda/iota expression and the clinicopathological features of gastric cancer.

Patients and methods: Gastric adenocarcinoma samples were obtained from 177 patients who underwent gastrectomy at the Yokohama City University Hospital between 1999 and 2004. Expression of aPKClambda/iota and E: -cadherin was examined immunohistochemically and compared with clinicopathological features of the tumors. Univariate and multivariate analyses were performed for both disease-specific and relapse-free survival.

Results: Overexpression of aPKClambda/iota protein was detected in 126 of the 177 (71.2%) gastric cancers. Immunohistological staining for aPKClambda/iota was stronger in gastric adenocarcinoma of intestinal type than diffuse type (p = 0.036), but was not correlated with E: -cadherin expression. A multivariate analysis suggested that nodal metastasis and aPKClambda/iota overexpression were prognostic factors for disease recurrence.

Conclusions: Our results suggested that aPKClambda/iota overexpression was a strong prognostic factor for gastric adenocarcinoma recurrence. As well as being a new prognostic indicator, aPKClambda/iota is also likely to be a novel therapeutic target for gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / secondary
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Female
  • Follow-Up Studies
  • Gastrectomy
  • Humans
  • Immunoenzyme Techniques
  • Intestinal Neoplasms / enzymology*
  • Intestinal Neoplasms / secondary
  • Intestinal Neoplasms / surgery
  • Isoenzymes / metabolism*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / enzymology*
  • Neoplasm Recurrence, Local / surgery
  • Prognosis
  • Protein Kinase C / metabolism*
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Isoenzymes
  • Protein Kinase C
  • protein kinase C lambda