Differential expression of hepatocyte growth factor in papillary and nodular tumors of the bladder.
BACKGROUND
The aim of this study was to investigate the expression of hepatocyte growth factor (HGF) and its receptor (c-met) during bladder tumorigenesis.


METHODS
HGF and c-met expression were analyzed immunohistochemically in matched samples of normal, dysplastic, and carcinoma specimens from 49 human bladders resected at the time of radical cystectomy for nonmetastatic transitional cell carcinoma (TCC). The tumors were composed of papillary (n = 22), nodular (n = 16) or mixed papillary and nodular (mixed; n = 11) components.


RESULTS
The normal urothelium showed no significant immunoreactivity to HGF. Expression of HGF was observed in 45.5%, 77.3% and 90.9% of specimens demonstrating mild, moderate, and severe dysplastic lesions adjacent to papillary TCCs, respectively, whereas all of the papillary TCC samples were positive for HGF. No immunoreactivity for HGF was found in dysplastic lesions from nodular tumors, and only 2 specimens had positive immunostaining for HGF in the tumor areas (1 showed weak immunostaining and 1 showed HGF immunostaining only in the deeper invasive compartment). Additionally, 3 nodular lesions taken from mixed tumors showed weak immunostaining for HGF while the concurrent papillary lesions were HGF-positive. There was a significant difference of HGF immunoreactivity between papillary and nodular tumors (P < 0.01). c-met immunostaining was consistently detected in all specimens. HGF and c-met immunoreactivity did not significantly correlate with tumor stage and grade, nor with overall patient survival irrespective of the tumor growth pattern.


CONCLUSIONS
These results suggest that HGF expression may play a significant role in the development of papillary TCC.
Department of Urology, Fukui Medical University, Yoshida, Japan.
B
B
Li
H
H
Kanamaru
S
S
Noriki
M
M
Fukuda
K
K
Okada
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015653:Cystectomy; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis; D012720:Severity of Illness Index; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met