Relationship of C-erbB-2 protein expression and gene amplification to invasion and metastasis in human gastric cancer.
BACKGROUND
Amplification and/or overexpression of the C-erbB-2 gene has been demonstrated in breast and gastric cancer and is thought to be involved in the process of gastric cancer metastasis.


METHODS
The expression of C-erbB-2 protein in human gastric cancer was examined by immunohistochemistry and amplification of the C-erbB-2 gene by Southern blot hybridization.


RESULTS
C-erbB-2 protein was located on the cell membrane of cancer cells in formalin-fixed, paraffin-embedded sections. Fourteen percent of specimens were positive for C-erbB-2, and no positive reaction was evident in noncancerous tissue. The presence of C-erbB-2 in gastric cancer was correlated with the depth of invasion, histologic type, growth pattern, and presence of liver metastasis. C-erbB-2 was found more often in advanced cancers (P < 0.05), papillary adenocarcinoma (P < 0.01), nonscirrhous cancer (P < 0.05), and cancers with liver metastasis (P < 0.01). The incidence of C-erbB-2 positivity in lymph nodes with metastasis was higher than in primary sites (P < 0.01) and was significantly higher in differentiated adenocarcinoma (P < 0.01). Patients with C-erbB-2-positive tumors had poorer survival rates those with C-erbB-2-negative tumors in the early stages (P < 0.001), but not in the advanced stages. Amplification of the C-erbB-2 gene was detected at the primary site and in metastatic nodes in the same case, and expression of the protein was also evident.


CONCLUSIONS
The expression and/or gene amplification of C-erbB-2 is related to invasion and nodal involvement in differentiated adenocarcinoma of the human stomach.
First Department of Surgery, Nippon Medical School, Tokyo, Japan.
T
T
Mizutani
M
M
Onda
A
A
Tokunaga
N
N
Yamanaka
Y
Y
Sugisaki
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000231:Adenocarcinoma, Papillary / Q000473:pathology; D002293:Adenocarcinoma, Scirrhous / Q000473:pathology; D015139:Blotting, Southern; D066246:ErbB Receptors; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors