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Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as for therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this study to: (a) examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis [microvessel density (MVD) and vascular endothelial growth factor (VEGF)]; and (b) determine the ultimate value of a histomorphological and a dynamic MRI approach by the correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) and standard parameters [the maximum signal intensity increase over baseline (SI-I) and the steepest signal intensity-upslope per second (SI-U/s)] were calculated from a contrast-enhanced dynamic MRI series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD and VEGF) were compared to MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found between MVD and A (P < 0.01) and SI-I (P < 0.05). No significant relationships were observed between VEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based on k21 and SI-U/s showed that tumors with high k21 and SI-U/s values had a significantly (P < 0.05 and 0.001, respectively) worse disease outcome than did tumors with low k21 and SI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD and VEGF) had any significant power to predict patient survival. It is concluded that in patients with uterine cervical cancer: (a) the pathophysiological basis for differences in dynamic MRI is MVD but not VEGF expression; (b) a functional, dynamic MRI approach (both standard and pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than are the current histomorphological-based markers of tumor angiogenesis; and (c) compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assess MVD or patient survival.

Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this project to: (a) examine the relationship between contrast-enhanced dynamic MRI-derived characteristics and histological microvessel density counts, a recognized surrogate of tumor angiogenesis, from primary or recurrent cancers of the uterine cervix; and (b) correlate these parameters with lymphatic involvement to characterize tumor aggressiveness in terms of lymphatic spread. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) were calculated from a contrast-enhanced dynamic MRI series in 55 patients (ages 25-72 years; mean, 50 years) with biopsy-proven primary (n = 42) or recurrent (n = 13) uterine cervical cancer. Both pharmacokinetic parameters were correlated to histologically determined microvessel density counts (factor VIII-related antigen) and other pathological tumor characteristics obtained from the operative specimens after radical surgery. In addition, the magnetic resonance and histological data were correlated to the presence or absence of lymphatic system involvement. Pharmacokinetic MRI-derived parameters (A and k21) increased with increasing histological microvessel density counts with r = 0.41 and 0.50, respectively. Lymphatic involvement was more comprehensibly assessed by the pharmacokinetic parameter k21 compared with histological microvessel density, resulting in a higher sensitivity, overall accuracy, and comparable specificity. Contrast-enhanced MRI parameters might prove to be applicable for estimation of tumor angiogenesis in uterine cervical cancer; thus, MRI may become an additional tool to characterize malignant progression in terms of lymphatic involvement in uterine cervical cancer.

Expression of mdm-2 mRNA was measured in 90 ovarian-cancer tissue specimens using the S1 nuclease assay, to investigate a possible association between MDM2 expression and prognosis. mdm-2 mRNA expression was an independent prognostic factor for patients with primary ovarian cancer, FIGO (International Federation of Gynecology and Obstetrics) stages III and IV (n = 57), who all received chemotherapy with carboplatin or cisplatin and cyclophosphamide. Median survival time for patients (FIGO stages III and IV) with no detectable expression of mdm-2 mRNA (n = 14) was 171 days, as compared with 839 days for patients (n = 43) with detectable mdm-2 mRNA (p = 0.0194; log-rank test). However, no association between mdm-2 mRNA expression and survival was observed for patients with FIGO stages I and II who did not receive chemotherapy. mdm-2 expression was not associated with FIGO stage, residual disease, histologic grade and type. Our results suggest that mdm-2, which is known to disrupt p53 function, sensitizes ovarian-cancer cells to cisplatin/cyclophosphamide, possibly by inhibition of p53-mediated G1 cell-cycle arrest and p53-stimulated nucleotide-excision repair.

Glutathione, glutathione S-transferases alpha and pi, and aldehyde dehydrogenase are associated with resistance to carboplatin and/or cyclophosphamide in cell lines. Therefore, we examined whether the expression of these factors in ovarian cancer tissue specimens is associated with resistance of the patients to combination chemotherapy with cyclophosphamide/carboplatin. Ovarian cancer tissue specimens were taken intraoperatively from 139 patients and frozen in liquid nitrogen, and the contents of glutathione S-transferases alpha and pi, total glutathione, and aldehyde dehydrogenase activity were determined. No association between the levels of glutathione S-transferases alpha and pi or aldehyde dehydrogenase activity in tumor tissue and the survival time was observed in patients with primary ovarian cancer. Significantly higher levels of aldehyde dehydrogenase were observed in FIGO stage I and II compared to FIGO stage III and IV tumors (P = 0.019, Wilcoxon test, two sided). The median survival time was significantly longer in patients with primary ovarian cancer with a tumor glutathione content of <4.9 microg/mg protein compared to patients with a tumor glutathione content of > or =4.9 microg/mg protein (P = 0.047). However, glutathione was not an independent prognostic factor, but was significantly associated with FIGO stage resulting in higher levels in FIGO stage III and IV tumors than in FIGO stage I and II tumors (P = 0.0094, Wilcoxon test, two sided). In conclusion the glutathione content was associated with progression of ovarian carcinomas but neither glutathione nor glutathione S-transferases alpha and pi or aldehyde dehydrogenase were independent factors of resistance to cyclophosphamide/carboplatin.

The oncogene specific mRNA of c-erbB-2 was detected by the S1 nuclease protection assay in 95 ovarian cancer specimens. In 79 primary carcinomas, we found 16 (20%) with strong expression, 13 (17%) with weak expression, 4 (5%) with very weak expression, and 46 (58%) with no expression. In 3 of 16 recurrencies (19%) a strong expression of c-erbB-2 mRNA was detected, in 2 (12%) weak expression was detected, and in 11 (69%) no expression of c-erbB-2 mRNA was detected. Kaplan-Meier analysis revealed no significant association between strong expression of c-erbB-2 mRNA and survival of the 79 patients with primary cancer. However, in the subgroup of patients with FIGO (International Federation of Gynecology and Obstetrics) stages III and IV (n = 60) a shorter median survival time (12 months) was obtained for patients with strong c-erbB-2 mRNA expression compared to patients with no, very weak, and weak c-erbB-2 mRNA expression (25 months, P = 0.04). In addition, strong expression of c-erbB-2 mRNA did not depend on histologic grade, histologic type, and FIGO stage. Adverse prognostic factors include histologic type (serous carcinoma), high grade, high stage (FIGO stages III and IV), and residual of tumor after surgery. From our results we conclude that for all patients (FIGO stages I-IV) strong expression of c-erbB-2 mRNA is not a prognostic parameter, but in the subpopulation of patients with FIGO stage III and IV only, an association between strong c-erbB-2 mRNA expression and shorter median survival time was found, although statistical significance was weak (P = 0.04).

The incidence of the carcinoma of the cervical stump is reported in the literature between 0.1-3%. The operative treatment as well as the radiation therapy is more difficult and complicated in relation to the cervical malignancy of an "intact" uterus. On the other hand the supracervical uterus-amputation offers advantages versus the classical hysterectomy. So many endoscopic experienced groups prefer this operative technique. SEMM performs an additional stanza of the cervix and corpus in order to remove the cervical adenocells. This procedure was simulated with the help of an in vitro model to answer the question of facultative adenocells in the remaining cervix. 41 uteri and the resected stanzas were histologically examined. Adenocells could be detected in 68.3 % of the cervical hulls. The transformation zone could be resected totally in all cases. Taking into account these results we can conclude, that the combination of the supracervical hysterectomy with a cervix-corpus-stanza could reduce the risk of a cervical stump-carcinoma. Because of remaining adenocells in the cervical hull, this special carcinoma-risk can't be excluded after an interval of at least 20-25 years.

The surgical therapy of vulvar carcinoma requires a subtle planning. A diagnostical excision of the lesion allows the ascertainment of histologic prognosis factors. On this basis, the surgical procedures should be designed. For all surgical defects, a panel of save plastic reconstructive methods have been developed, that allows favourable functional and cosmetic results.

Objective: In the search for the optimal treatment of advanced cervical cancer, the identification of valid prognostic factors obtainable without histopathologic investigation of the entire tumor and the locoregional lymph nodes is of paramount interest. Tumor microvessel density has recently been demonstrated to correlate strongly with disease aggressiveness in breast cancer and other malignancies., Methods: We established a computerized image analysis system to quantify tumor microvascularity by using the closest-individual method, which determines the distribution of distances from random points within the tumor to the closest microvessel (DTCMV). Tumor microvascularity was assessed in paraffin sections of two cylindrical 2 x 20-mm core biopsies obtained transvaginally from the 12 and 6 o'clock positions of each tumor and then immunohistochemically stained for Factor VIII-related antigen. The oncologic relevance of tumor vascularity is studied in an open prospective trial., Results: Tumor vascularity was quantified in 42 patients with cervical cancers > 3 cm in largest diameter, FIGO stages Ib-IVa. This new parameter representing pathophysiological tumor-host interactions was independent of various other patient and tumor characteristics, including age, FIGO stage, tumor size, differentiation, lymph node metastases and lymphatic space involvement. Thirty-nine patients were treated with curative intent either by primary surgery (n = 22) or radiation (n = 17). After a median observation time of 18 months (range 4-41 months), the patients with higher tumor vascularity (mean DTCMV < 83 microns) had significantly shorter disease-free (P = 0.025) and overall (P = 0.032) survival probabilities than patients with lower tumor vascularity (mean DTCMV > or = 83 microns). Cox regression analysis identified tumor vascularity as the strongest independent prognostic factor in this group of patients., Conclusions: The assessment of tumor microvascularity by computerized image analysis of defined tumor biopsies could become a novel means of predicting tumor aggressiveness in non-early cervical cancer.

In 250 patients with node-negative breast cancer and no systemic adjuvant therapy the impact on the prognosis of the variables age, histological tumour type, tumour size, histological grade, receptor status and localisation of the tumour within the breast, was studied. Patients were followed over a mean period of 60 (range 7-164) months. In a subset of 124 cases additional examination of the growth fraction rate, detected by immunohistochemical determination of antibody Ki-67 and semiquantitative measurement of the stained tumour cell nuclei was performed. In 43 cases, measurement of S-phase fraction by flow cytometry was also performed. By univariate analysis, the histological tumour type (ductal/non-ductal), histological grade and growth fraction rate (< = 20%/> 20% tumour cell nuclei stained by antibody Ki-67) were found to exert a significant influence on distant disease-free and overall survival. Cox' multivariate regression exhibited histological tumour type and growth fraction rate to be independent predictors of distant disease-free and overall survival. Additionally, age was found to be an independent variable of distant disease-free survival. Measurement of growth fraction rate by immunohistochemical detection of Ki-67 antigen is a fairly simple and easily applicable procedure. It should be discussed whether a growth fraction rate of more than 20% could be an indication for adjuvant chemotherapy in patients with node-negative breast cancer.

In spite of the development of various techniques for the formation of a neovagina, the longterm results are often disappointing, especially if the simpler methods (dilation, ectopic pouch formation, epithelium transfer) have been applied. The more complex surgical techniques such as musculo/fasciocutaneous and colon flaps are associated with a significant risk of severe complications. For certain operative situations necessitating vaginal reconstruction, adequate procedures are still missing. Based on surgico-anatomic investigation of the vascular territories of the myoperitoneal anterior abdominal wall, we introduce the use of myoperitoneal composite flaps from the deep inferior epigastric artery angiosome as a novel surgical principle for vaginal reconstruction and report on the experience with the first two patients.

The occurrence of the p 53 gene mutation in breast carcinoma tumour cells, leads to the accumulation of mutant p 53 protein types, whose consequence is the loss of the negative regulation normally exercised by the p 53 gene, which is considered to act as a tumour suppressor. It is possible to demonstrate the presence of mutant p 53 protein types in tumour cell nuclei by applying immunohistochemical procedures to paraffin sections (Clon DO 1, Dianova). We tested 482 primary breast carcinomas for the presence of these proteins, and positive immunohistochemical findings for mutant p 53 proteins were recorded in 21.6% of the cases. In another 14.3% of these breast carcinomas, less than 10% of the tumour cells exhibited positive staining. In the other 64.1% of cases, the immunohistochemical findings for p 53 proteins were entirely negative. Independent of the immunohistochemical staining results, we performed a retrospective analysis of the disease course of this group of primary breast carcinomas: it emerged, that p-53-positive breast carcinomas had a significantly less favourable prognosis as compared to primary tumours, which were negative or weakly positive for this protein group. The accumulation of p 53 proteins in tumour cell nuclei is correlated with negative oestrogen- and progesterone-receptor status, as well as with the degree of proliferation exhibited by the breast carcinoma. Such accumulation is, in contrast, unaffected by the tumour stage, its histological grading, menopausal status, and the overexpression of c-erb B2.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: Are newer histologic investigations helpful in the evaluation of the prognosis of vulvar carcinoma?, Methods: 147 primary squamous cell carcinomas of the vulva were examined for overall- and disease-free survival (mean observation 59.6 months)., Results: A significance in prognosis was found for FIGO-stage, a new-created histologic grade, p53- and vimentin-expression and amount of T-lymphocytes in tumoral stroma. Unfavourable prognosis was detected for tumors with elevated growth fraction, high proliferating cell-compartment (S + G2 + M) and increased cytokeratin-8-expression., Conclusions: These investigations are able to describe the malignant potential of a vulvar carcinoma and should therefore influence the decision for a modified radical therapy.

We determined the growth fraction in 549 primary breast carcinomas using monoclonal antibody Ki-67. With respect to the course of disease, significant differences emerged for the whole collective as well as among the node-positive tumors. We paid special attention to the node-negative (N0) carcinomas in the group, the aim being to differentiate a prognostically unfavorable subgroup in this otherwise favorable collective. Owing to the comparative rarity of clinical events, our findings for such tumors failed to attain statistical significance; however, a strong clinical trend indicating an adverse prognosis for both overall and disease-free survival emerged for tumors exhibiting a high growth fraction. One-quarter of these patients had received adjuvant treatment. In the group exhibiting high levels of Ki-67 reactivity, significantly less favorable findings with respect to overall survival were observed among the untreated patients. The present results seem to confirm previous indications that antibody Ki-67 is of value in assessing the prognosis of N0 breast cancer.

In a prospective study conducted since 1983, the hormone-receptor status of primary breast carcinomas was investigated using immunohistochemical (ER-ICA, PgR-ICA) and biochemical (DCC) methods. The degree of immunohistochemical staining was evaluated according to the immunoreactive score (IRS) devised by Remmele and Stegner [Frauenarzt 28, 41-43 (1987)]. The findings obtained using the biochemical radioactive-ligand-binding assay (cutoff level, 20 fmol/mg) and those obtained using qualitative immunohistochemical methods were in agreement in 72.5% (ER-ICA) and 72.2% (PgR-ICA) of cases. For the 789 cases of primary breast carcinoma examined, postoperative data were available for a mean follow-up period of 48 months. Using the statistical procedure of Kaplan-Meyer to analyze the probability of disease-free and overall survival, it emerged that ER-ICA- and PgR-ICA-positive breast carcinomas exhibited the most favorable course of disease. Breast carcinomas with negative immunohistochemical findings for both types of receptor were found to have a significantly less favorable disease course. Semiquantitative evaluations of the staining results using the IRS failed to yield significant differences among the 12 IRS groups. Neither the percentage of positive tumor cells nor the immunohistochemical staining intensity proved to be prognostically useful parameters for predicting the course of disease. In comparison to the established biochemical method for the demonstration of hormone receptors, however, the immunohistochemical procedure was found to be superior with respect to prognostic meaningfulness, particularly in the group with conflicting biochemical and immunohistochemical findings with respect to hormone-receptor status. Using Cox analysis, the prognostic usefulness of the immunohistochemical test was compared with that of certain established prognosis parameters (pT, pN, grading, Ki-67), from which it became apparent that PgR-ICA has the greatest prognostic value, with the most lasting influence on the course of disease. The results of the present study demonstrate that, with respect to the prognostic value of its findings, the immunohistochemical test for hormone receptors is superior to the biochemical procedure.

With regard to clinical diagnosis and prognosis, intrauterine infection continues to pose major problems for obstetricians. In recent years serum assay of CRP, an acute phase protein, has become firmly established in the obstetric management of premature rupture. We investigated the relationship between histologically confirmed chorioamnionitis and maternal and fetal inflammation parameters in 69 patients on the basis of inflammation of the membranes, placenta and cord occurring in histomorphologic stages. Our results show the C-reactive protein to be a sensitive and specific indicator of chorioamnionitis and closely correlated with both the histologic stage and the severity of the chorioamnionitis. We therefore advocate adoption of the histologic result as the "gold standard" for evaluating subclinical and clinically manifest forms of intrauterine infection.

The discussions on the pros and cons of obstetric screening for connatal infections have been going on for years. We, therefore, conducted a prevalence study of the most common connatal infections. HIV infection, rubella and syphilis were not subjects of this study. We analysed the relevance of these infections in 512 pregnant women and their newborn infants at the moment of delivery. Further serological tests were run three months post partum, if necessary even for a longer period. Cytomegaly IgG antibodies were found in 46% of the examined women, IgM antibodies in 1.3%. Women under the age of twenty and women of low social standing showed the highest rate of prevalence of infection with CMV. The prevalence of IgG antibodies against parvovirus B 19 was 29%. In 10 mothers, positive IgM titers were found at the time of delivery. In all these women, pregnancies had been uneventful. However, 9 mothers exhibited a significantly raised abortion rate within the last 20 months before delivery. 7 of 512 women turned out to be HBs antigen carriers, 3 women and their babies were anti-HCV positive. The prevalence of toxoplasmosis IgG antibodies was 36%, of IgM antibodies 5.3%. By further investigation (Toxo ISAGA, Toxo IgA) we were able to detect one child with connatal toxoplasmosis. We conclude, that screening for parvovirus B 19 and hepatitis C is required only, if there are contact or clinical hints that the patients might have acquired either one of these infections. But we postulate, that a routine screening programme for hepatitis B and toxoplasmosis should be carried out in all pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS)

Between 1984 and 1990, twenty-four patients suffering from advanced primary (7) or recurrent (17) valvular carcinoma were treated by posterior exenteration and myocutaneous reconstruction of the defect. During a follow-up of 34 months, the overall survival was 49%. Eight patients died. Tumour diameter and tumour-free margins of the resected specimens were the most important prognostic factors. In all cases, an improved quality of life could be achieved by the operation. It is concluded that, even in extremely difficult situations, posterior exenteration, followed by plastic reconstruction entails an essential benefit for the patient.

The expression patterns of intermediate filament proteins of primary and metastatic endometrial (n = 18) and ovarian (n = 24) adenocarcinomas were analyzed by immunocytochemistry using a panel of specific antibodies and by gel electrophoresis of cytoskeletal preparations, followed by immunoblotting. All cells of all endometrial adenocarcinomas studied contained the "simple epithelial"-type cytokeratins (CKs) 8, 18, and (mostly) 19, with variable numbers of cells also positive for CK 7 and vimentin. In addition, most of these tumors contained individual cells or groups of cells that were positive for the stratification-related CKs 4, 5, 6, 13, 14, and 17. The latter CKs were often associated with squamous cell foci, but were also found in some single (nonsquamous) tumor cells, indicative of early stages of squamous cell differentiation. Ovarian carcinomas of various histologic types and grades contained predominantly CKs 7, 8, 18, and 19. Serous, endometrioid, and anaplastic tumors, but not mucinous and clear cell tumors, also contained minor amounts of stratification-related CKs in variable combinations, mostly including CK 4. In all tumor types except mucinous tumors, vimentin was consistently detected in variable proportions of tumor cells which, however, were rather low in anaplastic carcinomas. Surprisingly, glial filament protein was detected in a minor proportion (< or = 20%) of tumor cells in seven of 14 serous and endometrioid ovarian carcinomas and in three of 18 endometrial carcinomas. These different intermediate filament expression patterns of müllerian duct-type carcinomas, only partly related to the morphologic appearance of the specific type of tumor, might reflect the multipotentiality of differentiation of müllerian duct-derived epithelia. Cytoskeletal features of potential diagnostic value, especially in metastatic carcinomas, are discussed.

Cardiotocography (CTG) is to be considered today's most sensitive monitoring tool for the functional surveillance of placental performance during parturition. 351 cardiotocographically monitored singleton pregnancies were used as patient material for fine tissue examination of the state of maturity of the villi of the relevant placentas. In histological assessment, placental diagnoses are allocated to defined CTG changes; in particular, however, the identification of reserves, capable of maturing (immature intermediate villi in the centres of the placental subdivisions or placentones), is subject to separate scrutiny. The following results emerge clearly: terminal placentas without maturing potentials, prematurely matured placentas and placentas with deficiency of terminal villi, as well as the absence of immature intermediate villi in the centers of the placentones, are connected with a suspected prepathological or pathological CTG assessment. The histological groups have the lowest incidence of the normal oscillatory type and normal oscillatory frequency and have the highest proportion of abnormal CTG assessments according to the Hammacher score. The absence of the identification of potential maturing reserves (immature intermediate villi) is associated with the highest incidence of Caesarean sections (29.8%). These results show, that the physiological maturing potentials (immature intermediate villi) which can be identified up to term are a histological indication towards regular placental performance, even in labour.

We investigated the oestrogen-receptor content (ER-ICA) of 614 tissue samples taken from breast carcinomas (all obtained from patients at the Universitäts-Frauenklinik, Mainz FRG) using immunohistochemical procedures. Since the findings of follow-up studies as well as estimates of survival probability (according to the procedure of Kaplan-Meier) for 334 of the primary breast carcinomas were available, it was possible, to assess the prognostic value of the immunohistochemical results. The percentage of receptor-positive tumour cell nuclei (i.e. the heterogeneity of the tumour), as opposed to the staining intensity, proved to be the most useful criterion of the IRS, whose cut off level was determined as being IRS 1. Regardless of their lymph node status, mammary carcinomas which were immunohistochemically positive for estrogen receptors, were found to have a significantly better short-term prognosis, than breast tumours which were negative for such receptors. In the case of certain breast carcinomas exhibiting contradictory findings (i.e. ER-ICA positive but biochemically negative for oestrogen receptors), the present immunohistochemical method provided the most accurate assessment of the biological behaviour and development of the tumor. Therefore, ER-ICA represents a valuable prognostic criterion, which when complemented with PR-ICA, should facilitate attaining optimal selection of patients suitable for endocrine therapy.

In 147 primary breast carcinomas, over-expression of NEU-protein was detected immuno-histochemically. 20 tumours (13.6%) showed a positive reaction. Correlations with established prognostic factors, showed a significant relationship to unfavourable histological grading and negative oestrogen receptor status, as well as to the negative status of both oestrogen and progesterone receptors. However, no correlation could be demonstrated with the progesterone receptor alone. Only a trend without significance was demonstrated to the tumour size and proliferation rate-indicated by the Ki-67 antibody. No correlation existed to the status of the axillary nodes. Overexpression of NEU-protein proved to have a significant influence on the disease-free survival and overall survival in a median follow-up time of 31 months. Nevertheless, this could be shown only for tumours with metastasis in axillary nodes, but not for nodal negative tumours. A possible Longer follow-up time is necessary, to show a difference of results for the latter group.

245 breast cancer tissues were analysed immunohistochemically, using monoclonal antibody Ki-67, which spezifically reacts with a nuclear antigen of proliferating cells and represents the so-called growth fraction. According to the number of positive cells, three Ki-score categories (I-III) were established. The results were compared with prognostic variables (Histological grading, DNA-cytophotometry), staging parameters, immunocytochemical (ER-ICA, mPRI), and biochemical (DCC) hormone receptor assay. We found a good correlation between Ki-67 and grading (Bloom and Richardson): G 1-tumors had small growth fractions, in contrast to G-III carcinoma, which showed a high percentage of Ki-Score III. Receptor negative cases had a large growth fraction and receptorpositive ones showed an uniform distribution. The comparison between Ki-67 and tumor spread or DNA-Cytophotometry showed no correlation. The majority of 31 recurrent tumors not only had a large number of positive cells, but also a definite dependence was found between Ki-Score and length of the disease-free period. Ki-67 seems to be an important immunohistochemical marker of breast cancer, which contributes to the individual assessment of the disease and can possibly give predictions on tumor development and response to radiation and systemic therapy.