Expression of the hepatocyte growth factor/c-Met pathway is increased at the cancer front in breast carcinoma.
Expression of hepatocyte growth factor (HGF) and c-Met (HGF receptor) has been reported in many neoplasms. We investigated coexpression of HGF and c-Met to determine the role of the HGF/c-Met pathway in breast carcinoma, especially at the cancer front. Eighty-eight cases of carcinoma of the breast were studied by immunohistochemistry and by in situ hybridization for HGF and c-Met expression. The staining pattern was termed "front accentuation pattern" when it was most conspicuous at the cancer front. HGF and c-Met proteins were expressed in cancer and stromal cells, with autocrine and paracrine patterns. The front accentuation pattern of c-Met was observed in cancer cells, but not in stromal cells. The front accentuation pattern was not observed in HGF. Coexpression of HGF and c-Met at the cancer front was correlated with histologic grade, reduced patient survival and a high Ki-67 labeling index. Our findings suggest that the HGF/c-Met pathway acts primarily as a mitogen, especially at the cancer front, in a paracrine manner and affects some clinical factors, including patient survival.
Edakuni
G
G
Department of Pathology, Saga Medical School, Nabeshima 5-1-1, Saga, Japan. g9604@post.saga-med.ac.jp
Sasatomi
E
E
Satoh
T
T
Tokunaga
O
O
Miyazaki
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000032:analysis; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015996:Survival Rate
D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met