Phosphorylation of epidermal growth factor receptor and chromosome 7 polysomy in gastric adenocarcinoma.
OBJECTIVE
To investigate the phosphorylation of epidermal growth factor receptor (EGFR) and its potentially associated chromosomal aberrations in gastric adenocarcinoma.


METHODS
Phosphorylated EGFR (pEGFR) was detected by immunohistochemistry on 145 specimens including 60 tumoral, 60 non-tumoral, 12 tumor-adjacent intramucosal dysplasia from patients with gastric adenocarcinoma and 13 mucosae from cancer-free patients. EGFR gene amplification and chromosome 7 (Chr-7) polysomy were detected by fluorescence in situ hybridization.


RESULTS
Positivity of pEGFR was found in 50 tumoral (83.3%) and 42 non-tumoral specimens (70.0%). There was an association between tumoral and non-tumoral zones on immunostains of pEGFR (r = 0.353, P = 0.006). Nuclear pEGFR usually presented in mucosae with Helicobacter pylori infection, stromal reaction or vascular invasion. Cytoplasmic pEGFR was correlated with local cancer extension (r = 0.337, P = 0.014) and inversely related with gastrokine 2, which had been previously detected in the same specimens. Eleven intramucosal dysplastic specimens were also positive for pEGFR while 13 mucosae from cancer-free patients were all negative. No EGFR gene amplification was observed. However, seven tumor specimens showed Chr-7 polysomy (11.7%) in which 5 were strongly positive for pEGFR.


CONCLUSIONS
EGFR phosphorylation may be one of the mechanisms that promote tumor initiation and expansion in gastric adenocarcinoma. Detection of pEGFR with analysis of its nuclear or cytoplasmic patterns could be clinicopathologically valuable. Chr-7 polysomy may partially contribute to EGFR activation in gastric adenocarcinoma, although its role does not predominate.
Department of Pathology, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
Fan
F
Zhang
Jian Min
JM
Tang
Li
L
Wang
Jing Ying
JY
Shen
Lin
L
Zheng
Ping Ping
PP
Wu
Mei
M
Zhang
Zhao Wen
ZW
Yan
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C503073:GKN2 protein, human; D009363:Neoplasm Proteins; D066246:ErbB Receptors