Potential prognostic significance of p185(HER2) overexpression with loss of PTEN expression in gastric carcinomas.
OBJECTIVE
The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185(HER2)) that has partial homology with the epidermal growth factor receptor and shares intrinsic tyrosine kinase activity. The phosphatase and tensin homolog mutated on chromosome ten (PTEN) gene product is a protein tyrosine phosphatase that participates in modulating the phosphoinositide 3-kinase pathway which has antagonizing activity to protein tyrosine kinase. The authors investigated the correlation between clinicopathologic variables including survival and the overexpression of the p185(HER2) with loss of PTEN expression in gastric adenocarcinoma patients.


METHODS
The protein expression of p185(HER2) and PTEN was examined by immunohistochemical stain in paraffin-embedded tissues of 94 (M:F, 52:42) gastric adenocarcinoma patients by using monoclonal antibody, and the results were related to clinicopathological variables and survival.


RESULTS
p185(HER2) overexpression correlated positively with lymph node metastasis, distant metastasis, AJCC classification, higher relapse rate. Patients with overexpression of p185(HER2) were found to have significantly lower disease-free survival (P = 0.003) and overall survival (P = 0.0004). Loss of PTEN expression correlated positively with depth of invasion (T stage) and was more frequent in the advanced stage. The patient group with p185(HER2) overexpression and loss of PTEN expression showed significantly shorter disease-free and overall survival (P = 0.03, P = 0.01) than the other groups.


CONCLUSIONS
Our observations suggest potential prognostic significance of p185(HER2) overexpression with PTEN loss in gastric adenocarcinoma patients. This opens up the possibility of considering p185(HER2)and PTEN as a therapeutic target in gastric cancer.
Im
Seock-Ah
SA
Section of Oncology/Hematology, Department of Internal Medicine, Seoul National University, College of Medicine, 28 Yongondong Chongnogu, Seoul, 110-744, Korea. moisa@snu.ac.kr
Lee
Kyung Eun
KE
Nam
Eunmi
E
Kim
Do Yeun
DY
Lee
Joo-Ho
JH
Han
Ho-Seong
HS
Seoh
Ju-Young
JY
Park
Hae-Young
HY
Cho
Min-Sun
MS
Han
Woon Sup
WS
Lee
Soon Nam
SN
D000230:Adenocarcinoma / Q000737:chemistry* / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015536:Down-Regulation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D016019:Survival Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases