Immunohistochemical expression of HGF, c-MET and transcription factor STAT3 in colorectal tumors.
By immunohistochemistry, we have investigated the expression of hepatocyte growth factor (HGF), HGF-R or c-met and the transcritor factor STAT3 in a series of 80 colorectal tumours (40 adenomas and 40 adenocarcinomas). The expression of HGF, c-met and STAT3 was revealed in 40/40 (100%) of adenomas and in 26/40 (65%) of adenocarcinomas; the remaining 14/40 (35%) carcinomas expressed c-met but failed to express HGF and STAT3. Positive immunoreaction score was defined through the number of stained cells: low (1-10%), moderate (11-50%) and high (>51%). In adenomas, the HGF immunoreaction was high in 33 (82.5%) and moderate in 7 (17.5%); the c-met staining was high in 3 (7.5%) and moderate in 37 (92.5%); and the STAT3 reactivity was high in 25 (62.5%) and moderate in 15(37.5%). In carcinomas, the HGF immunoreaction was moderate in 21 (80.7%) and low in 5 (19.2%); the c-met staining was high in 14 (35%), moderate in 25 (62.5) and low in 1 (2.5%); and the STAT3 reactivity was moderate in 17 (65.3%) and low in 9 (34.6%). In both type of lesions, HGF and c-met showed a membranous and cytoplasmic location. In adenomas, STAT3 was detected in cytoplasm and nucleus and in carcinomas it was limited to cytoplasm. While the HGF/c-met/STAT3 expression in adenomas was significantly different from carcinomas (c2 = 17, p < 0.0001), no correlation was found among HGF, c-met, or STAT3 immunostaining with histotype or degree of dysplasia in adenomas and the same for histotype, grading or staging in carcinomas. These features, suggesting a role of the HGF/c-met/STAT3 signal in colon tumorigenesis, indicate that a reduced expression of HGF and c-met is associated to progression of adenoma into carcinoma.
Trovato
M
M
Dipartimento di Patologia Umana, Padiglione D, Policlinico Universitario G. Martino, 98125 Messina, Italy. mariatrovato@tin.it
Vitarelli
E
E
Grosso
M
M
Alesci
S
S
Benvenga
S
S
Trimarchi
F
F
Barresi
G
G
D000236:Adenoma / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met