p53 and HER-2 alterations in renal cell carcinoma.
OBJECTIVE
To investigate protein expression and genetic aberrations of p53 and HER-2 in renal cell carcinoma (RCC) as well as possible association of p53 and HER-2 abnormalities with the tumor behavior of RCC.


METHODS
Formalin-fixed and paraffin-embedded tissue blocks from 70 patients with RCC were studied. Protein expression of p53 and HER-2 was assessed immunohistochemically. Following deoxyribonucleic acid extraction from the paraffin sections using a microdissection technique, p53 gene mutations within exons 5 to 8 were examined by polymerase chain reaction (PCR) single-strand conformation polymorphism and HER-2 gene amplification by a differential PCR.


RESULTS
Of the 70 RCCs, 16 (22.9%) showed protein expression of p53, with 7 (10%) demonstrating mutations within exons 5 to 7. Additionally, 28 RCCs (40%) displayed protein expression of HER-2, with 12 (17.1%) demonstrating gene amplification. All cases showing p53 mutations or HER-2 amplification represented protein expression of p53 or HER-2, respectively. No cases with negative immunostaining for p53 or HER-2 protein displayed positive results at gene level. Statistical analysis revealed a close relationship between p53 protein expression and the tumor grade, as well as a significant association of HER-2 protein expression and gene amplification with the tumor stage of RCC.


CONCLUSIONS
Our observations suggest that the abnormalities of p53 and HER-2 may be involved in the pathogenesis of RCC and that other mechanisms leading to protein expression of p53 and HER-2 may coexist within a single tumor in addition to the genetic aberrations.
Zhang
X H
XH
Department of Urology, Kagawa Medical University, Kita-gun, Japan.
Takenaka
I
I
Sato
C
C
Sakamoto
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018739:Oncogene Proteins v-erbB / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D018739:Oncogene Proteins v-erbB; D016159:Tumor Suppressor Protein p53