Overexpression of c-Met/hepatocyte growth factor receptors in human prostatic adenocarcinoma.
Hepatocyte growth factor (HGF) and c-met proto-oncogene product (c-Met) have varied biological functions in different tissues and have been implicated in mitogenic, motogenic and morphogenic responses in both organ regeneration and carcinogenesis. Some studies have suggested that the overexpression of c-Met and epidermal growth factor receptor (EGFR) are associated with growth advantage, while transforming growth factor-beta receptor II (TGF beta R II) is associated with growth disadvantage of human prostatic adenocarcinoma. However, it is unclear if the expression of c-Met correlates with the expression of EGFR and TGF beta R II, and with the proliferative status of human prostatic adenocarcinoma. Using immunohistochemical staining with anti-c-Met (C-12), anti-EGFR (NCL-EGFR) and anti-TGF beta R II (L-21) antibodies, we determined the frequency of expression of c-MET, EGFR, and TGF beta R II respectively in a series of 134 radical prostatectomy specimens. We evaluated the relationship between the expression of these receptors and clinicopathological characteristics. Overall, c-Met immunostaining was detected in 54 of 134 (40.3%) cases, EGFR in 45 (33.6%) and TGF beta R II in 64 (48.4%). The overexpression of c-Met was significantly more common in poorly differentiated (P < 0.0001) and in the diffusely infiltrated specimens (P < 0.0005). In contrast, TGF beta R II was significantly overexpressed in the well differentiated specimens (P < 0.0001) and associated negatively with c-Met (P < 0.0001). Overall, these data suggest that c-Met/HGF receptor and TGF beta R II overexpression may be involved in the differentiation of human prostatic adenocarcinoma, c-Met with de-differentiation and TGF beta R II with differentiation.
Inoue
K
K
Department of Urology, Kochi Medical School, Japan.
Chikazawa
M
M
Karashima
T
T
Iiyama
T
T
Kamada
M
M
Shuin
T
T
Furihata
M
M
Ohtsuki
Y
Y
D000230:Adenocarcinoma / Q000737:chemistry*; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis* / Q000276:immunology; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D018125:Receptors, Transforming Growth Factor beta; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II