PTEN expression and mutation in colorectal carcinomas.
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor is a phosphatase that antagonizes the phosphoinositol-3-kinase/AKT signaling pathway and suppresses cell survival as well as cell proliferation. To investigate the molecular role of PTEN expression and mutation in colorectal carcinomas, we performed immunohistochemistry to detect PTEN expression on tissue microarray containing colorectal carcinomas and corresponding adjacent non-cancerous mucosa. PTEN mutation was studied from exon 1 to 9 by PCR, followed by direct sequencing. PTEN expression was then compared with clinicopathological parameters and prognosis of the tumor, including caspase-3 expression. In the present study, PTEN expression was stronger in the adjacent non-cancerous mucosa than carcinoma (P<0.001). Low PTEN expression was positively correlated with tumor size, depth of invasion, lymphatic invasion, lymph node metastasis, higher Dukes staging and reduced caspase-3 expression (P<0.05), but not with venous invasion or differentiation (P>0.05). Univariate analysis suggested that the patients without PTEN expression had shorter survival than the patients with its expression (P=0.003). Multivariate analysis indicated that lymphatic invasion, venous invasion, and PTEN expression were independent prognostic factors for overall colorectal carcinomas (P<0.05). The analysis of mutations revealed only one synonymous mutation in exon 8 (codon 312 Asp: GACright curved arrow GAT). These results suggested that down-regulated PTEN expression was involved in the pathogenesis, invasion and metastasis of colorectal carcinomas possibly by regulating the balance between apoptosis and proliferation. PTEN expression may be a good marker for the prognosis of colorectal carcinoma.
Li
Xiao-Han
XH
Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Sugitani 2630, Toyama, Japan.
Zheng
Hua-Chuan
HC
Takahashi
Hiroyuki
H
Masuda
Shinji
S
Yang
Xiang-Hong
XH
Takano
Yasuo
Y
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D053148:Caspase 3 / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D046888:Tissue Array Analysis; D055815:Young Adult
D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D053148:Caspase 3