One hundred benign and malignant primary liver tumours were screened immunocytochemically for alpha-fetoprotein (AFP), alpha 1-antitrypsin, alpha-human chorionic gonadotropin, carcinoembryonic antigen (CEA), keratin and vimentin. Alpha-fetoprotein was found in 16/63 (24%) hepatocellular carcinomas and in two hepatoblastomas. When comparing tissue positivity for AFP with tumour differentiation, grade 1 hepatocellular carcinomas were found to be negative, while 21% of grade 2, 36% of grade 3 and 16% of grade 4, respectively, stained positively. Alpha-fetoprotein positive cells were present in 9/10 hepatocellular carcinomas with serum levels exceeding 5000 ng/ml, but were absent in 17 tumours with serum AFP levels below 5000 ng/ml. All tumours other than hepatocellular carcinomas and hepatoblastomas were AFP negative. Carcinoembryonic antigen was present in 72% of cholangiocarcinomas, but was demonstrated in only one hepatocellular carcinoma. This exception was a combined hepatocellular-cholangiocarcinoma in which CEA expression was restricted to the cholangiocellular part. Alpha 1-antitrypsin was found in 4/63 hepatocellular carcinomas, in 2/2 fibrolamellar carcinomas and in 2/18 cholangiocarcinomas. Alpha-human chorionic gonadotropin was detected in one hepatocellular carcinoma and was strongly expressed in both fibrolamellar carcinomas. Weak staining for keratin was seen in most tumours with hepatocellular differentiation. All cholangiocarcinomas, in contrast, were strongly labelled with the keratin antibody. Co-expression of keratin and vimentin was observed in seven poorly differentiated hepatocellular carcinomas and three cholangiocarcinomas as well as in the two hepatoblastomas. The findings suggest that AFP is a diagnostic but rather insensitive immunocytochemical marker for hepatocellular differentiation in malignant liver tumours; CEA and keratin may help in discriminating cholangiocarcinomas from hepatocellular carcinomas.

Purpose: Breast cancer (BC) is the most frequent female carcinoma and the major cause of death in women aged 35–50 years. The total number of patients surviving BC and especially the morbidity rate of patients below the age of 55 years has increased significantly in the last several years. As a consequence, the number of BC patients suffering from the long-term effects of estrogen deficiency due to adjuvant treatment is increasing. At present, hormone replacement therapy (HRT) following BC treatment is applied individually and mainly depends on the severity of postmenopausal symptoms (PMS) experienced by these patients. Patients and Methods: In a retrospective study (total n = 185 BC patients, 64 with and 121 without HRT), the effect of HRT during or after adjuvant therapy [chemotherapy and/ or (anti-) hormonotherapy] has been investigated. The surveillance period was up to 60 months. Evaluated were HRT effects on (1) PMS measured by a comprehensive life quality questionnaire, (2) bone mineral density (BMD) measured by osteodensitometry and (3) morbidity as well as mortality rates. Results: Both groups did not differ with regard to tumor stage, lymph node involvement, metastasis, grading, and steroid hormone receptor status. A reduction in PMS was significant in women taking HRT (p < 0.001), especially in the subgroup of women ≤50 years (p < 0.0001). For both age groups, the median reduction in BMD (z-score) was less in women receiving HRT (≤50 years: without HRT –1.99 vs. with HRT –0.95, p < 0.05; >50 years: without HRT –2.29 vs. with HRT –1.19, p < 0.01). There were no statistically significant differences regarding morbidity and mortality (p = 0.29). Conclusion: In this study of BC patients, the use of HRT shows positive effects on PMS and BMD. There was no significant influence on morbidity or mortality. However, a reevaluation of HRT in the routine management of BC patients should await the results of prospective randomized trials.

Proliferation of breast and endometrial cells is under the control of ovarian steroid hormones (SHs) such as oestrogen and progesterone. They mediate diverse physiological functions via interaction with nuclear-localised steroid hormone receptors (HRs). The SH receptor complex modifies the expression of SH-regulated genes by binding to conserved binding sites in their promoter region or through cross-talk with other transcription factors. In non-malignant tissues, HRs are in balance with other factors regulating proliferation, differentiation and apoptosis. While dysfunction of the regulatory mechanisms is a part of malignant transformation, functional SH receptors can promote growth of SH-responsive tumours. Therefore, anti-hormones that block the interaction of steroid hormones with the SH receptor are useful tools for the treatment of SH-responsive carcinomas. However, a portion of ER-positive breast cancers and most endometrial cancers do not respond to anti-oestrogens and continued treatment results in hormone resistance, mostly without loss of the ER. This review focuses on the mechanisms of action of hormones and anti-hormones in breast and endometrial carcinomas.

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Seventy specimens of normal endometrium (n = 13) and cervix (n = 12), endometrial hyperplasia (n = 4), cervical dysplasia (n = 20), endometrial (n = 11) and cervical carcinoma (n = 8) and uterine metastases of mammary carcinomas (n = 2) have been analysed for c-erB-2 expression with immunohistochemistry employing a monoclonal anti ERBB-2 antibody and Northern-blot hybridization using single stranded RNA probes. In comparison with the c-erbB-2 mRNA expression level found in normal samples, two advanced and poorly differentiated endometrial adenocarcinomas (FIGO IV) and two ductal mammary carcinomas which had metastasized to the uterus, together with three carcinomas in situ of the cervix, showed c-erbB-2 enhanced transcription level. All other endometrial samples including adenomatous hyperplasia and nine endometrial carcinomas (FIGO I), and all other lesions of squamous epithelial origin displayed transcriptional activities at or below the baseline level. Immunohistochemical study of ERBB-2 protein expression showed staining in most samples, although different in distribution and intensity. Staining of endometrial glands was seen in unevenly distributed cells or cell clusters. In contrast, for endocervical glands, labelling was observed distinctly on basally located cells (reserve cells) and at the subapical side of luminal cells. Faint labelling of the basal cell layer was also observed in squamous epithelia. It was more pronounced in severe cervical dysplasia and carcinoma in situ. In carcinomas of glandular origin, dedifferentiation was accompanied by an increase in cytoplasmic labelling, whereas the intensity of staining was not related to differentiation in squamous cell carcinomas. While data derived from Northern blots are suggestive of c-erbB-2 overexpression to indicate an advanced and dedifferentiated state of tumours of glandular origin, staining with an anti-ERBB-2 antibody occurred in both normal and atypical squamous and glandular epithelia and may indicate regular proliferation and/or differentiation-associated events.