High Expression of Atypical Protein Kinase C lambda/iota in Gastric Cancer as a Prognostic Factor for Recurrence

The atypical protein kinase C lambda/iota (aPKC lambda/iota) is involved in several signal transduction pathways that influence cell growth, apoptosis, and the establishment and maintenance of epithelial cell polarity. Overexpression of aPKC lambda/iota has been reported in several cancers and been shown to be associated with oncogenesis. However, the expression and role of aPKC lambda/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 aPKC lambda/iota expression and the clinicopathological features of gastric cancer. Gastric adenocarcinoma samples were obtained from 177 patients who underwent gastrectomy at the Yokohama City University Hospital between 1999 and 2004. Expression of aPKC lambda/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. Overexpression of aPKC lambda/iota protein was detected in 126 of the 177 (71.2%) gastric cancers. Immunohistological staining for aPKC lambda/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 aPKC lambda/iota overexpression were prognostic factors for disease recurrence. Our results suggested that aPKC lambda/iota overexpression was a strong prognostic factor for gastric adenocarcinoma recurrence. As well as being a new prognostic indicator, aPKC lambda/iota is also likely to be a novel therapeutic target for gastric cancer.