Effects of short-term tamoxifen administration in patients with invasive cervical carcinoma.

Cervical cancer is not considered a hormone-responsive tumor in spite of the presence of estrogen receptors (ER) and progesterone receptors (PgR) in some of them. Endocrine treatments have not achieved clinical responses, however, tamoxifen has been reported to induce PgR and to inhibit cell growth of many cervical carcinoma cell lines. In this study we investigated whether tamoxifen administration affects the histopathological characteristics of cervical cancer and the expression of ER, PgR, HER-2/neu and p53 protein. Nineteen patients with invasive cervical cancer free of previous treatments were studied. The triphenylethylene antiestrogen tamoxifen was given orally during 10 days (20 or 40 mg/day). Pre- and post-tamoxifen biopsies were evaluated using slides stained with hematoxylin and eosin and immunostained (ER, PgR, HER-2/neu, p53, PCNA, keratin, heat shock protein 27,000 daltons). Estrogen receptors were present in 37% and PgR in 16% of the biopsies from untreated patients. Only one case that was PgR-negative before tamoxifen administration showed weak PgR-positivity following antiestrogen administration. No obvious changes were observed in ER, HER-2/neu and p53 proteins. A statistically significant decrease in the number of mitotic figures was obtained in 16% (3/19) of the post-tamoxifen biopsies and two of them showed higher differentiation. The results showed that tamoxifen did not induce changes in estrogen-regulated proteins in cervical cancer. However, the data showed that certain cervical carcinomas had changes in their proliferation and differentiation levels following tamoxifen administration. These findings suggest that tamoxifen may affect some cervical cancer tissues by a hormone-independent mechanism(s).

Analysis of a 24-kilodalton (KD) protein in the human uterine cervix during abnormal growth.

The authors have previously studied the presence and distribution of a 24-kilodalton (KD) estrogen-regulated protein in the human normal cervix (Am J Obstet Gynecol 1986; 155:1090-1096). This protein has recently been identified as a heat-shock protein, and in order to continue its study the authors have now examined its expression in preneoplastic to neoplastic cervical samples. The study involved 53 patients, the presence of 24-KD protein together with keratin and carcinoembryonic antigen (CEA) was investigated by immunohistochemical analysis. Cytosol samples from 15 patients with squamous cervical carcinomas were also studied by the Western blot technique, and the presence of estrogen receptors was analyzed biochemically. The 24-KD protein was observed in cervical intraepithelial neoplasias (CIN), but it was not useful to identify the different degrees of CIN examined. The 24-KD protein, keratin, and CEA were predominantly expressed in well and moderately differentiated squamous carcinomas in the more differentiated areas, and the protein was also found in cervical adenocarcinomas. The presence of 24-KD protein did not correlate with that of estrogen receptors in squamous cervical carcinomas. The Western blot and the immunohistochemical studies revealed that the antibody to 24-KD protein does not cross-react with epitopes of CEA and keratins.