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


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.
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Ryo
R
Takagawa
Kazunori
K
Akimoto
Yasushi
Y
Ichikawa
Hirotoshi
H
Akiyama
Yasuyuki
Y
Kojima
Hitoshi
H
Ishiguro
Yoshiaki
Y
Inayama
Ichiro
I
Aoki
Chikara
C
Kunisaki
Itaru
I
Endo
Yoji
Y
Nagashima
Shigeo
S
Ohno
D000230:Adenocarcinoma / Q000201:enzymology* / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005743:Gastrectomy; D006801:Humans; D007124:Immunoenzyme Techniques; D007414:Intestinal Neoplasms / Q000201:enzymology* / Q000556:secondary / Q000601:surgery; D007527:Isoenzymes / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000201:enzymology* / Q000601:surgery; D011379:Prognosis; D011493:Protein Kinase C / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D000099293:Protein Kinase C-lambda
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda