P16/MTS1 and pRB expression in endometrial carcinomas

p16(MTS1/CDKN1) and the retinoblastoma protein Rb are both involved in nega tive regulation of G1/S progression in the mammalian cell cycle. Inactivati on of one of these tumour suppressor genes is involved in many malignant ru mours, and in some studies a negative correlation of p16 and Rb expression has been found. In order to study this interaction in endometrial carcinoge nesis, we investigated 36 endometrial carcinomas, 11 cases of hyperplasia. 23 normal endometrial samples, and two uterine carcinoma cell lines by immu nohistochemistry or RT-PCR. Rb was expressed in normal endometrial epitheli um, hyperplasia, cell lines, and most carcinomas; negative immunostaining w as only detected in I of 36 rumours. In contrast, p16 expression was weak i n normal endometrium and increased in most cases of hyperplasia, but negati ve or minimally positive in 74% of the carcinomas and the HeclB adenocarcin oma cell line, and there was no significant association with Rb immunostain ing. Strikingly high p16 expression was found in foci of squamous metaplasi a within hyperplastic or carcinomatous tissue. Deletion and mutation analys is of the p16 gene was performed in DNA from microdissected tumour samples and cell lines. No p16 deletion was found, and mutations were detected in o nly one tumour sample and SkutlB uterine mixed mesodermal tumour cells. Our data indicate that in spite of low or absent p16 expression, genetic alter ations of the p16 and Rb tumour suppressor genes are rare in endometrial ca rcinogenesis.