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The development of cancer in humans is considered as a multistep process ultimately leading to clinically detectable disease and further progression of the tumour. By use of cytometric techniques it has been possible to perform quantitative measurements and detect qualitative alterations in malignant tumours. This mainly applies to DNA aberrations and deviations in nuclear size and morphology. Such alterations may also be present for a long period prior to malignant, invasive growth, i.e. at a preneoplastic stage. A survey of available data on such preneoplastic changes is given. Since the type of aberrations is both dependent on the tissue of origin and the tumour type, this must always be taken into consideration. A particularly rapid expansion has taken place in the field of flow cytometry, where high resolution measurements of cellular DNA content as well as cell cycle distribution and other parameters can be performed shortly after sampling of the tissue. It is expected that cytometric methods will be used in future diagnostics of early cancerous growth in several organ systems, including the skin, the gastrointestinal tract, the urinary bladder, the breast and female genital organs.

Tissue samples taken from endometrial carcinomas as well as from normal and hyperplastic endometria were tested for oestradiol receptors. Roughly one and the same amount of receptors was recordable from all three tissue groups. In premenopausal women, receptor levels were lowest in the advanced phase of secretion. All tumour patients so far have survived without recurrence. Therefore, no correlation has been established, as yet, between receptor level and prognosis, in a way similar to what has been found in cases of mammary carcinoma.

In 49 carcinomas of the endometrium of varying clinical stages the estrogen and progesterone receptors were studied by charcoal absorption methods. The cases were studied between 1979 and 1981. 64% of the investigated cases were receptor positive, 35% were receptor negative. Estrogen receptors were detected in 61% and progesterone receptors in 49% of the cases. Both estrogen and progesterone receptors were detected in 45% of the cases. The receptor status was correlated with the clinical stage, the microscopic differentiation and the age of the patient. In 30 cases with a follow-up of more than 3 months it was attempted to determine the prognostic value of the steroid receptor status in endometrial carcinoma. The treatment possibilities with progestational agents and antiestrogens and with tamoxifen were discussed in view of the receptor status.

Determination of the tissue concentration of hormone receptors in gynaecological malignancies has achieved a great importance over the past few years. In carcinoma of the breast this not only constitutes an excellent prognostic parameter, receptor-positive cases usually having a much better prognosis, but also reliably predicts the response to endocrine treatment: the higher the receptor concentration, the higher the remission incidence under hormonal treatment. With regard to the response to chemotherapeutic treatment the predictive value of receptor determinations is still a matter of dispute. In both carcinoma of the breast and carcinoma of the endometrium there is a good correlation between the degree of differentiation and the concentration of receptors. Since the response to treatment with progestational agents depends on the concentration of progesterone receptors, induction of this receptor by means of antioestrogenic medication can be used therapeutically. In ovarian carcinoma a similar distribution of hormone receptors is found. Whether receptor concentration in ovarian carcinoma is related to prognosis and response to endocrine treatment is still under investigation. It can be assumed that determination of hormone receptor concentrations will become an integral part of the management of gynaecological malignancies.

Prognostic criteria of cervical and uterine carcinomas can be important for both physician and patient. Compared with patients not subjected to surgical treatment, a multitude of prognostic criteria must be investigated in operated women via the systemic examination of the surgical specimen, reaching beyond the weight attached to the clinically assumed staging. These criteria enable quantitative and qualitative characterization of the carcinomas allowing individualisation of therapy adapted to the tumour.

A variety of test systems have been developed for predicting the efficacy of cytotoxic drugs in the treatment of individual malignant human tumors. The present paper reports on the author's experience with Volm's short-term chemosensitivity test and Hamburger and Salmon's stem-cell assay. In the Volm test the influence of adriamycin on the incorporation of radioactively labelled uridine in an individual tumor cell suspension was investigated. Comparison with a cytostatic-free control permitted conclusions to be drawn with regard to the proliferation-related chemosensitivity. The stem-cell assay is based on the capacity of certain tumor cells, the so-called stem cells, to form colonies in a bilaminar soft agar system. The growth of the colony of pre-incubated cytostatics was evaluated in relation to that of untreated tumor cells. The Volm test was successful in 63 (95%) out of a total of 66 tests conducted. Twelve tumors were chemosensitive in the test and 51 chemoresistant. In the stem-cell assay, growth of a colony which permitted chemosensitivity to be tested was only found in 27 out of 183 tests. The criterion of chemosensitivity with a reduction of at least 50% in the number of cells in the colony by at least one cytostatic was satisfied by 14 (29%) of the 49 stem-cell assays which could be evaluated, there being no differences between breast and ovarian carcinomas. The two test systems indicated the chemosensitivity correctly in less than 50% of 49 retrospectively evaluated courses of disease. In contrast, resistance was predicted correctly in 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

The nuclear estrogen receptors ERn were determined in 12 carcinomas whose cytoplasm contained progesterone receptors PRc but no estrogen receptors ERc. ERn were found in 9 of the tumors. Their concentration correlated to those of PRc and reached a mean of only 20% of the ERn concentrations found in ERc+/PRc + carcinomas. These results suggest that in carcinomas of the ERc-/PRc+-type, originally present cytoplasmic estrogen receptors induce the synthesis of progesterone receptors in a concentration corresponding to that of the nuclear receptors, following translocation by endogenous estradiol in the nucleus.