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The application of various mathematical models for the identification of binding parameters in steroid receptor studies is discussed. In contrast to the usual statistical error considerations a deterministic error analysis based on the Euclidian norm and condition numbers is included. The predicted sensitivity behaviour with respect to data scattering is in good agreement with the experimental results.

Silicone prostheses are known to impair the diagnostic evaluation of the breast. The authors report about a case of a small carcinoma of the breast, which was examined by MRI, ultrasound and mammography. The diagnostic capabilities of these imaging modalities are discussed and MRI is presented as a new possible tool for an improved evaluation of breasts with silicone implants.

It is possible to predict to some extent the hormone receptor status of carcinomas of the breast via cytomorphology of fine needle biopsy specimens. In most cases the cytologically highly differentiated carcinomas are receptor-positive and the poorly differentiated ones receptor-negative if the cases are arranged in the sequence of increasing conspicuousness of cellular criteria of malignancy. Since visual microscopic examination is subjective by nature, quantification was carried out by means of high-resolution image analysis using Pappenheim stained slides. The quantitative image analysis grading system basing on this method proved to be even more efficient than visual diagnosis.

Between August 1985 and November 1987, 150 patients with 167 biopsy-proved lesions were examined with magnetic resonance (MR) imaging enhanced with gadolinium diethylenetriaminepentaacetic acid, mammography, and palpation. Of these patients, 113 with 123 lesions were also examined with ultrasound. Enhancement above 300 normalized units (NU) on MR images was considered significant; between 250 and 300 NU, borderline; and below 250, nonsignificant. All 27 fibroadenomas and 70 of 71 carcinomas showed significant enhancement; one carcinoma showed borderline enhancement. Nonproliferative dysplasia showed nonsignificant enhancement in 15 of 16 cases and significant enhancement in one, whereas proliferative dysplasia showed usually diffuse enhancement varying from nonsignificant (five of 30 cases) to borderline (five of 30 cases) to significant (20 of 30 cases). In the nonblind evaluation of the modalities, MR imaging compared favorably. When limitations of the technique were considered, MR imaging seemed beneficial as a supplement in selected, diagnostically difficult cases.

The authors report about their preliminary experience with MRI in the diagnosis of breast disease. 50 breast masses in 41 consecutive patients have been evaluated by MRI and mammography, some of which have been evaluated by ultrasound, as well. All masses have consequently been biopsied. They include 32 carcinomas, 1 secondary malignant lymphoma, 4 fibroadenomas, 2 papillomas, 3 cysts, 1 hamartoma and 5 dysplastic nodules. Advantages and disadvantages of MRI of the breast are discussed. Possible future indications are suggested for selected cases.

55 patients with altogether 60 breast masses have been examined postoperatively by plain MR, MR with Gd-DTPA and mammography at our institution. All breast carcinomas and fibroadenomas did enhance significantly. Non-proliferative dysplasia, normal breast tissue and scar tissue did not enhance significantly. Borderline enhancement has been found in cases of proliferative dysplasia. The diagnostic accuracy has been improved by MR with Gd-DTPA. Advantages have been an improved visualization of tumors in dense breasts, an improved differentiation between irregular dysplasia and carcinoma and an improved differentiation between post-therapeutic changes (after radiation, surgery or silicon implants) and carcinoma. Nevertheless both technical improvements and further clinical experience is necessary.

One hundred thirty-four pre- and perimenopausal patients presenting with metastatic breast cancer (median age, 42 years; range, 25 to 55) were treated with goserelin (Zoladex [ICI 118 630]; ICI Pharma, Plankstadt, Germany) a long-acting gonadotrophin-releasing hormone (GnRH)-analogue depot formulation, injected subcutaneously every 4 weeks, as a first-line therapy. One hundred eighteen patients were evaluable for response. Serum concentrations of estradiol, luteinizing hormones (LH), and follicle-stimulating hormones were significantly suppressed by Zoladex. Mean serum estradiol values fell into the range of castrated or postmenopausal women within 2 to 3 weeks of therapy. This suppression was maintained for the duration of therapy. Overall objective response was: 12 (10.2%) complete remission; 41 (34.7%) partial remission; 33 (28.0%) no change; and 32 (27.1%) progression. In responders, the median time to response was 4 months (range, 2 to 11 months), median duration of response was 8 + months (range 2 to 24 months), and median time to progression was 11 + months (range, 5 to 30 months). Objective responses were seen for different sites of metastases: loco-regional (62.5%), bone (46.7%), visceral (45.0%), and multiple (35.1%). Tumor remission was more common in patients in which the primary tumor was estrogen receptor (ER)-positive (49.3%) or ER-unknown (44.0%), but appreciable response rates were also observed in ER-poor patients (33.3%). Zoladex depot was well tolerated both locally and systemically. It produced effective castration and the objective response rates and duration of remission are at least comparable to those seen following oophorectomy; however, the side effects are less. The use of depot Zoladex avoids the psychological trauma and operative morbidity of the irreversible operative castration.

In a preliminary study 20 patients underwent breast examinations by magnetic resonance (MR) imaging without and with Gd-DTPA as contrast medium. All carcinomas enhanced, whereas dysplastic tissue enhanced slightly or not at all. Significant additional diagnostic information was available on the Gd-DTPA examinations in at least four of 20 cases compared with MR without contrast medium and X-ray mammography. Our preliminary results indicate that MR imaging of breast using Gd-DTPA may be helpful for the evaluation of dense breasts and the differentiation of dysplasia and scar tissue from carcinoma.

Doubtful and established breast cancer risk factors were checked in a case/control study. Multivariate analysis with the logistical regression approach resulted in a usable separation of the cases from the controls on the basis of the five dichotimized variables: age at birth of first child, family history, Quetelet index, breast complaints, and a behavior score. On the basis of probability, the risk patterns were summarized in six risk categories, and a maximum 70-fold risk was thus established. The proportion of incidence represented by the risk groups was then estimated from distribution in the control group. Approx. 5% of new cases originate in 30% of the female population aged under 30, but approx. 51% originate in a mere 10%. Hence it is logical to use risk factors for early detection based on risk.

The incorporation of N-ethylmaleimide into the 30,000-Mr component of beef-heart mitochondria has been studied as a function of various ligands to the ADP/ATP carrier and the isolation of the N-ethylmaleimide-labeled protein is reported. 1. The incorporation of N-ethylmaleimide into the 30,000-Mr component is specifically stimulated by ADP and ATP. Thus by differential incorporation of N-ethylmaleimide, the 30,000-Mr component is preferentially labeled. 2. Addition of carboxyatractylate inhibits, whereas bongkrekate tolerates, the incorporation of N-ethylmaleimide. 3. After solubilization by Triton the purification of N-ethylmaleimide-labeled protein is facilitated in the presence of bongkrekate but not of carboxyatractylate, in agreement with the postulated existence of only a bongkrekate-N-ethylmaleimide-protein complex. The labeled protein was purified to homogeneity on hydroxyapatite in Triton and subsequently, after denaturation in dodecylsulfate, on Sepharose 6B. 4. The identify of the isolated labeled protein with the formerly isolated bongkrekate-protein or carboxyatractylate-protein complexes is confirmed by the isoelectric point and amino acid composition. 5. Two moles of N-ethylmaleimide must be incorporated into the 30,000-Mr component in order to inhibit fully the binding of one mole carboxyatractylate. This corresponds to one -SH group per unit.

132 solid breast masses have been examined at our institution by MR and have consequently been histopathologically correlated. T1- and T2-weighted SE and multi-echo sequences have been evaluated visually. It was found that signal intensities of tissues on T2-weighted images correlated with the contents of fibrosis, cells or water. Thus in some lesions (which consisted of different tissue components), a characteristic internal structure was visible on T2-weighted images, reflecting their histopathologic structure. Corresponding to their different composition, differences of signal intensity have also been noted between those fibroadenomas with a high contents of fibrosis and all other well-circumscribed breast lesions (fibroadenomas, carcinomas). However, for the majority of lesions with irregular contours a discrimination based on signal intensities or calculated T1- and T2-values did not seem possible. This overlap can also be explained by the macroscopically similar composition (amount of fibrosis, water or cells) of benign and malignant irregular lesions.

Epidemiological and experimental investigations have led to the hypothesis that the growth of malignant melanoma is induced by hormones. The demonstration of free-hormone binding sites in melanoma tissue may help to determine the validity of this hypothesis, as receptors are necessary for the transformation of hormonal action. The DCC assay with subsequent saturation analysis was used for the demonstration of specific cytoplasmatic binding sites of steroid hormones. The presence of free-cytosolic estrogen-, progesterone- and glucocorticosteroid receptors was investigated in 50 melanoma samples from 46 patients. In 20 of the 50 specimens, free estrogen and progesterone receptors were found. Free-glucocorticosteroid receptors we found in 10 cases. The use of four fold-labeled estradiol (2,4,6,7-[3]-17 beta-estradiol) in the DCC assay produced a false-positive demonstration of free-estrogen receptors. Tyrosinase hydroxylates estradiol at the C2 level of the steroid. Using fourfold labeled estradiol, tritium is separated at the C2 position, thus forming radioactive water in the cytosol which mimics high, free-estrogen binding sites. The use of twofold-labeled estradiol or L-dopa in the experiments with fourfold labeled estradiol produced no false-positive determinations of estrogen receptors. The demonstration of receptors in malignant melanomas was unaffected by the sex of the patient. Also, the type of malignant melanoma, the invasion level, and the prognostic index did not show a correlation with the presence of the various hormone receptors. In metastases, free steroid hormone receptors were detected less often than in the primary tumor.

In a prospective study CA 125 serum levels of 99 patients with ovarian cancer were determined serially. 50 of 55 patients with second-look-laparotomy elevated levels initially had. We were interested in particular in the correlation between CA 125 and the histological findings at second-look operation. In 16 patients there was no residual tumor, CA 125 was in the normal range. In 34 the women tumor tissue was demonstrated; CA 125 was elevated in 14 patients, so there were 20 patients with false negative CA 125 serum levels. No false positive CA 125 values were found. In all patients with elevated tumor marker the residual tumor was histologically confirmed at second look. To verify a complete remission, a second-look operation will have to be performed in spite of a negative tumor marker, since active tumor tissue might still be present. In patients with elevated CA 125 a second-look laparotomy should be avoided at this time.

36 patients with cervical carcinoma were treated with cytostatic drugs in our department between January 1986 and December 1988. Following histological diagnosis by staging laparotomy or by means of a scalenous biopsy, 12 patients received primary chemotherapy and 3 patients received adjuvant chemotherapy following a radical hysterectomy, because of the histological extent of the disease. Twenty-one patients were treated by chemotherapy because of recurrent disease. Treatment consisted at first of a combination of cisplatin and etoposide, followed in August 1987 with a combination of carboplatin and ifosfamide. More than 90% of patients, the SCC, CEA or both tumour markers were elevated before the treatment, so that the course of the tumour markers during chemotherapy could be followed. All patients showed primary response to therapy, the tumour marker levels fell rapidly to normal after one or two cycles. None of these patients showed tumour progression while the tumour marker levels were within the normal range. Clinical remission was not obtained in those patients with levels, which remained high or rose again following an initial decrease. After only two cycles of chemotherapy, levels began to rise further and continuation of therapy did not seem justified. Chemotherapy is often the only available therapy for advanced cervical carcinoma or recurrent disease, even though the results of treatment in squamous cell carcinoma remain poor. The course of SCC and/or CEA levels can help in an early decision, whether or not the patient would profit from a continuation of the therapy.(ABSTRACT TRUNCATED AT 250 WORDS)