[Male breast cancer: history, epidemiology, genetic and histopathology]. / Das Mammakarzinom des Mannes - Historie, Epidemiologie, Atiologie, Genetik und Histopathologie.

Breast carcinoma is a rare disease in men. The incidence is 1 per cent of the incidence in women. Relative hyperestrogenemia and environmental factors seem to be important for the development of the disease. In recent years, germline mutations have been observed in male breast carcinoma patients in several genes, BRCA2, the androgene receptor gene and PTEN. Suspected genetic factors include the cell-cycle checkpoint kinase (CHEK)2 protein truncating mutation 1100delC that has been shown to confer a 10-fold increase of breast cancer risk in men. The c.1-34T > C 5' promoter region polymorphism in cytochrome P450c17 (CYP17), a key enzyme in the biosynthesis of estrogen, has been associated with male breast cancer risk, hemochromatosis gene (HFE) mutations, the mismatch repair genes (hMSH2, hMLH1,hPMS1,hPMS2) and PTEN mutations (Cowden syndrome) are associated with male breast cancer. The majority of tumors is seen retromamillarly. Ductal carcinoma in situ comprises 5-10 % of all cancers. In case of invasive growth, 85-90 % are invasive ductal carcinomas (NOS), 2.5 % are papillary tumors; lobular cancers are exceptionally rare. About 3/4 of all cancers express estrogen and progesterone receptor with increasing positivity with increasing patient age. HER-2 / neu overexpression is seen in the same frequency as in female breast cancer. Poor prognostic factors are tumor size > 2 cm, poorly differentiated tumors, receptor negativity, axillary lymph node involvement and more than four affected nodes.

Childhood leukaemia incidence around French nuclear installations using geographic zoning based on gaseous discharge dose estimates.

The present study investigated for the first time the incidence of childhood leukaemia (1990-2001) around French nuclear installations using a geographic zoning based on estimated doses to the red bone marrow due to gaseous radioactive discharges. The observed number of cases of acute leukaemia (O=750) in 40 km2 centred on 23 French nuclear installations between 1990 and 2001 was lower than expected (E=795.01), although not significantly so (standardised incidence ratio SIR=0.94, 95% confidence interval=(0.88-1.01)). In none of the five zones defined on the basis of the estimated doses was the SIR significantly >1. There was no evidence of a trend in SIR with the estimated doses for all the children or for any of the three age groups studied. This study confirmed that there was no evidence of an increased incidence of childhood leukaemia around the 23 French nuclear sites.

S100 as an immunohistochemically-detected marker with prognostic significance in endometrial carcinoma.

BACKGROUND: Several studies have indicated that dendritic cells (DC) participate in anti-tumor immunity, possibly influencing the course of malignant disease. We tested whether tumor infiltration by S100+ DC could be a prognostic marker for endometrial cancer. MATERIALS AND METHODS: A retrospective study analyzing 115 tissue samples from patients with endometrial carcinoma and known histological grading as well as hormone receptor, Ki-67, Her-2/neu and p53 expression. Sections of paraffin-embedded endometrial tissue were immunohistochemically-stained with anti S100 antibody. Tumor infiltrating S100+ DC were counted via microscopic examination and calculated as S100+ DC per mm2 of tissue. RESULTS: Samples were divided into group 1: less than 10 S100+DC/mm2 (n = 44) and group 2: 10 or more S100+ DC/mm2 (n = 71). Correlation with clinico-pathological markers was calculated by Chi-square test. Compared to group 1, the DC-rich group 2 showed a higher level of differentiation (p=0.045), a lower overexpression of p53 (p=0.021) and less proliferation (p=0.028). DC infiltration was not correlated with Her-2/neu, hormone receptor status and FIGO-stage. Although no significant correlation could be seen, the DC-poor group samples seemed to correlate with a higher FIGO-stage compared to the DC-rich group. In uni- and multivariate analysis, DC infiltration proved to be a significant prognostic marker for adjusted survival but not for overall survival. CONCLUSION: Our results indicate that the immunohistochemical determination of S100+ DC could contribute to the identification of a high-risk subgroup and, therefore, would be a favorable prognostic factor for endometrial carcinoma. Our observation that pronounced DC infiltration is associated with good prognosis points to an important role of the host's immune system response for the clinical course of endometrial cancer.

French population exposure to radon, terrestrial gamma and cosmic rays.

In France, natural sources account for most of the population exposure to ionising radiation. This exposure varies widely with area. Radon and gamma-ray exposure data come from national measurement campaigns; cosmic doses were calculated from city altitude. These data were corrected for season of measurement, housing characteristics and population density to study their relationship with health indicators. The crude average of indoor radon concentrations was 89 Bq m(-3), and the average corrected for season and housing characteristics was 83 Bq m(-3) (range over districts: 19-297). Weighting by district population density yielded a national average of 63 Bq m(-3). Gamma-ray dose rates averaged 55 nSv h(-1) (23-96) indoors and 46 nSv h(-1) (25-85) outdoors; corrections did not change the means. Corrected cosmic annual doses averaged 0.28 mSv (0.27-0.38). These corrections estimated the radiation exposure of the French population more accurately and represented its distribution well, thereby allowing its study as a cofactor in ecological studies.

Simultaneous interdisciplinary counseling in German breast/ovarian cancer families: first experiences with patient perceptions, surveillance behavior and acceptance of genetic testing.

As part of a multicenter study supported by the German Mildred Scheel foundation we have established an interdisciplinary counseling setting for members of breast and/or ovarian cancer families. We offer simultaneous counseling by a team consisting of a geneticist, a gynecologist and a psycho-oncologist. Here we describe our counseling protocol and our first short-term experience with this interdisciplinary approach. Preliminary data on patient perceptions and behaviors in the context of DNA testing are reported. Overall, our counseling approach was perceived as beneficial both by the counselors and the consultants. A marked overestimation of the risk to develop breast and/or ovarian cancer was noted in the group of unaffected individuals from medium to low risk breast cancer families in contrast to an appropriate risk perception in members from high risk families. All participants shared many of the same expectations about genetic testing and counseling and appeared to base their decision-making about testing on the risk classification given by the genetic counselor. The reported participation in gynecological cancer prevention programs was high in all families at risk, but was less sufficient in unaffected as compared to affected persons. Although current data on BRCA1/BRCA2 mutation analyses render testing in medium to low risk individuals questionable, our findings emphasize the importance of genetic counseling and education in all risk categories of breast and/or ovarian cancer families.

Frequency of BRCA1 mutation 5382insC in German breast cancer patients.

OBJECTIVE: The aim of the study was to determine the frequency of the BRCA1 mutation 5382insC in German breast cancer patients with and without prior knowledge of a family history of breast cancer. METHODS: Two groups of breast cancer patients were tested for the presence or absence of the 5382insC mutation using a PCR primer mismatch assay. A sample of 248 patients unrelated by genealogy was selected based on a history of breast and/or ovarian cancer in the families. In addition, a population-based sample of 800 unselected breast cancer patients was included in the analysis. Three intragenic DNA markers D17S1323, D17S1322, and D17S855, located at BRCA1 introns 12, 19, and 20, respectively, were utilized for allelic association studies as well as for haplotype analysis in 4 breast/ovarian cancer families. RESULTS: The 5382insC mutation was identified in 10/248 (4.0%) familial breast cancer patients and in 8/800 (1.0%) unselected cases. Allelic association studies and haplotype analysis revealed an association of allele Nos. "6" at D17S1323 (chi2 value = 9.34, P = 0.007), "5" at D17S1322 (chi2 value = 3.62, P = 0.171), and "4" at D17S855 (chi2 value = 11.34, P = 0. 002) with the mutation 5382insC. CONCLUSION: 5382insC constitutes a frequent BRCA1 mutation in German breast cancer patients. The significant allelic association between this mutation and two intragenic DNA markers (D17S1323, D17S855) and the elevated allele frequency at marker D17S1322 suggest an ancient founder in the German breast cancer population. The PCR primer mismatch assay described herein provides a rapid and reliable detection method for the recurrent 5382insC mutation and will be useful for the analysis of large breast cancer populations.

Endometrial carcinoma: immunohistochemically detected proliferation index is a prognosticator of long-term outcome.

AIM: To test which immunohistochemically detected tumour parameters are predictive of outcome in endometrial carcinoma. METHODS: A retrospective study of 300 patients diagnosed with endometrial carcinoma between 1980 and 1985, ensuring a follow up of at least 10 years. Paraffin wax embedded tissues from 236 patients with endometrial carcinoma were evaluated in terms of histological tumour type and grade, stage of disease, and certain immunohistochemical biological parameters. These parameters included the expression of oestrogen and progesterone receptors, the expression of p53 protein, the expression of the c-erbB-2 oncoprotein, and the expression of protease cathepsin D, together with the rate of cell proliferation. RESULTS: Using univariate analysis, the following parameters correlated significantly with adjusted survival: histological type (p = 0.025), grade (p = 0.00003), FIGO stage (p < 0.00001), proliferation rate (p = 0.00002), oestrogen receptor expression (p = 0.007), progesterone receptor expression (p = 0.0092), and p53 expression (p = 0.00028). These parameters also correlated significantly with both disease free and overall survival. There was a weak correlation of cathepsin D expression with survival, but no correlation of c-erb B-2 expression with survival. Using multivariate analysis, only FIGO stage (p = 0.0021), histological grade (p = 0.005), and proliferation rate (p = 0.0007) remained statistically significant prognosticators of adjusted survival as well as of disease free and overall survival. CONCLUSIONS: In addition to conventional histological parameters, the immunohistochemical determination of proliferative activity could contribute to the identification of a high risk subgroup of endometrial carcinomas. The other parameters tested were not of significant additional predictive value.

Prevalence of human papillomavirus DNA in cervical tissue. Retrospective analysis of 855 cervical biopsies.

The histopathologic features of 855 cervical biopsies were correlated with the presence of human papillomavirus DNA using in situ hybridization (ISH) with biotin labeled type specific probes for Human Papilloma Virus (HPV) types 6, 11, 16, 18, 31, 33 and 51. HPV-DNA was found in 18% (13/72) of cervical intraepithelial neoplasia I (CIN I), 30% (35/115) of CIN II, 28% (57(206) of CIN III, in 84% (21/25) of flat condyloma and in 13% (15/112) of normal cervical tissue. HPV DNA was detectable in 11% (5/46) of cervical adenocarcinoma and in 21% (59/279) of squamous cell carcinoma (SCC) of the cervix. High risk HPV types were identified more often than low risk HPV types in CIN I, CIN II, CIN III and SCC. HPV type 16/18 predominates over HPV types 31/33/51 in CIN I, flat condyloma and in SCC. The prevalence of HPV was strongly associated with the grade of differentiation of SCC. It was identified in 59% (23/39) of well differentiated SCC, in 18% (25/142) of moderately differentiated and in 11% (11/98) of poorly differentiated SCC.

[Rate of proliferation as a prognostic criterion in endometrial carcinoma--an immunohistochemical analysis with the monoclonal antibody KI-S1]. / Die Proliferationsrate als Prognosekriterium beim Endometriumkarzinom--eine immunhistochemische Analyse mit dem monoklonalen Antikörper KI-S1.

In a subset of 183 primarily operative treated patients of 300 patients with endometrial carcinoma an analysis of histological tumor type (n = 142), myometrial invasion (n = 115), stage (n = 114), immunohistochemically detected steroid receptor status, histologic grading (n = 152) and growth fraction, detected by immunohistochemical determination of antibody Ki-S1 (n = 130), was performed. The mean follow up was 9.1 years. By univariate analysis, age, myometrial invasion (< = 3/>3 mm), expression of steroid receptor, FIGO-stage, histologic grading and growth fraction were found to influence the overall survival rate significantly. Cox multivariate regression showed age, FIGO-stage and growth fraction to be independent predictors of overall survival. With respect to survival univariate analysis revealed progesterone receptor status, FIGO-stage, histologic grading and growth fraction as prognostic factors. By multivariate analysis FIGO-stage, histologic grading and growth fraction were found to be independent prognostic factors for survival. Multivariate and univariate analysis exhibited FIGO-stage, histologic grading and growth fraction rate to be independent predictors of a disease-free survival. Immunohistochemically detected growth fraction seems to be useful as an additional prognostic factor in endometrial cancer.

[Tainted femininity--traces of traditional menstruation myths in product advertising of feminine hygiene products]. / Befleckte Weiblichkeit--Spuren tradieter Menstruationsmythen in der Werbung für Produkte der weiblichen Intimhygiene.

OBJECTIVE: Does the portrayal of menstruation in menstrual product advertisements reflect cultural myths about menstruation? METHODS: We analyse the reception of menstruation in contemporary and historical menstruation product advertisements. RESULTS: In menstrual product advertisements, menstruation is depicted as an unclean attribute, discrediting an ideal femininity and creating the need to conceal it. CONCLUSION: This tendency to taboo menstruation in menstrual product advertising contributes--by conveying a negative definition of femaleness--to a negative self-perception, particularly in young women.

Immunohistochemically detected HER-2/neu-expression and prognosis in endometrial carcinoma.

Expression of the HER-2/neu proto-oncogene product was looked for immunohistochemically in 222 endometrial carcinomas in a retrospective follow-up study. The intensity of protein expression was correlated with patient survival. Median follow-up time was 4.8 years. In 109 (49%) of 222 endometrial carcinomas there was aberrant expression of HER-2/neu. HER-2/neu-expression did not correlate with p53-expression and proliferation rate, as determined immunohistochemically by the monoclonal antibody Ki-S1. In univariate statistical analysis aberrant HER-2/neu expression was not predictive of adjusted survival (p = 0.18) and of disease-free survival (p = 0.42). In multivariate analysis HER-2/neu-expression was not found to be an independent prognosticator (p = 0.099) as compared to FIGO-stage (p = 0.0001), histologic grade (p = 0.00099) and proliferation rate (p = 0.0013). Therefore immunohistochemically detected expression of HER-2/neu seems not to be a clinical prognosticator in endometrial cancer.

Significant decrease of maternal serum serotonin levels in singleton pregnancies complicated by the HELLP syndrome.

The purpose of this study was to compare peripartum maternal and umbilical cord serum serotonin levels in singleton pregnancies complicated by the HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) or by severe preeclampsia with those of appropriate controls. The study population comprised 14 primigravidae women with class 1 or 2 HELLP syndrome (platelet count < 50,000 or < 100,000/mm3, elevated transaminase levels, evidence of hemolysis) and 17 women with severe preeclampsia (American College of Obstetricians and Gynecologists criteria). Serotonin was measured in maternal serum immediately before delivery and in umbilical cord serum by a highly sensitive 125I-radioimmunoassay. The control groups comprised 31 women who had uncomplicated deliveries at term (control group I) and another 31 at the gestational age matched to that of each patient (control group II). Maternal serum serotonin concentration was 59.5 +/- 36.1 ng/ml (mean +/- SD) in the HELLP group, versus 94.9 +/- 40.5 ng/ml in control group I (p = 0.043, U-test) and 88.7 +/- 29.4 ng/ml in control group II (p = 0.048). Levels in the preeclampsia group (51.6 +/- 32.2 ng/ml) were not different from those in the HELLP group but were equally decreased when compared to control groups I (p = 0.009) and II (p = 0.003). We have observed a similar depression of serum serotonin concentrations both in severe preeclampsia and in the HELLP syndrome, reflecting the decreased platelet content of serotonin. It is uncertain whether these changes may be causally involved in the pathogenesis of hypertensive disorders of pregnancy. Decreased serum serotonin concentration may serve as an additional marker for platelet activation in preeclampsia and in the HELLP syndrome.

p53 protein in endometrial cancer is related to proliferative activity and prognosis but not to expression of p21 protein.

Expression of the tumor suppressor gene product p53 and the cyclin-dependent kinase inhibitor p21, which is transcriptionally activated by p53, was investigated and compared with patient survival in a retrospective longitudinal study of 202 cases of endometrial carcinoma. The median duration of follow-up was 4.3 years. P53 was observed immunohistochemically in 63 (31%) of the tumors and was found by univariate analysis to be related to reduced adjusted survival (p = 0.00028) and disease-free survival (p = 0.04). However, p53 expression was not found by multivariate analysis to be an independent prognostic factor when compared with FIGO stage, histologic grade, and proliferative activity, as determined by immunoreactivity for topoisomerase IIalpha with the antibody Ki-S1. Overexpression of p53 was related to histologic grade (p < 0.00001), proliferative activity (p = 0.0071), and inversely to progesterone receptor content (p = 0.042). Immunohistochemical identification of p21 was investigated in 95 cases and found to be positive in 19 (39%) of 49 tumors with p53 overexpression and in 13 (28%) of 46 tumors without p53 overexpression (p = 0.28). Expression of p21 is therefore not related to p53 expression, nor was it found to be related to proliferative activity. Strong expression of p21 was observed in tumors negative for progesterone receptors (p = 0.0028). P53 in endometrial carcinoma is not associated with induction of the cell cycle inhibitor p21, but is associated with an enhanced proliferative activity. The findings of multivariate analysis suggest that the prognostic significance of p53 is related mainly to cell proliferation.

[Postpartum rupture of a kidney cyst in familial polycystic kidney degeneration and HELLP syndrome]. / Postpartale Ruptur einer Nierenzyste bei familiärer polyzystischer Nierendegeneration und HELLP-Syndrom.

We present a case of polycystic kidney disease and HELLP syndrome with rupture of a renal cyst. 6 days after caesarean section at 30 weeks' gestation the patient developed severe abdominal pain with acute renal failure. The abdominal CT scan demonstrated a left perirenal hematoma.

[Premature termination of pregnancy in the 2nd and 3rd trimester. Serial administration of 1 mg gemeprost vaginal suppositories versus intravenous sulproston]. / Vorzeitige Schwangerschaftsbeendigung im II. und III. Trimenon. Serielle Applikation von 1 mg Gemeprost-Vaginalsuppositorien versus Sulproston intravenös.

Comparison of 1 mg Gemeprost-Vaginal Suppositories Serial Application versus Sulproston i.v.: Three different regimens for the termination of second and third trimester pregnancies by the use of prostaglandins (PG) were compared in a retrospective analysis. In group A (n = 16) terminations were attempted by continuous i.v. Infusion of Sulproston 9 hours after administration of a 3 mg-PGE2-vaginal tablet overnight. In group B (n = 22), i.v. Sulproston was started 2 hours after priming with 1 mg Gemeprost-vaginal suppositories. The outcome of these two regimens was compared with that of repeated administration of 1 mg Gemeprost-vaginal suppositories at 6-hourly intervals (group C, n = 25). In each group. If uterine contractions failed to appear after one day, the treatment was discontinued for a sleep rest over night and then resumed. Genetic disorders or fetal malformations were the most frequent reasons for termination. Patients with intrauterine fetal demise, rupture of the membranes, preterm labour or a ripe cervix (Bishop Score > 3) were excluded. Median time intervals from induction to abortion were 33 hours in group A and 23 hours in each Group B and C. The rate of fetal expulsions within 12, 24 and 36 hours in groups B and C were similar. Women of parity > or = 1 showed significantly shorter intervals than nulliparae in groups A and C. Only one woman (in group A) failed to expel after induction, in four other cases (in groups A and B) complications (local thrombophlebitis, bronchospasm) were noted. The serial administration of 1 mg Gemeprost-vaginal suppositories at 5-hourly intervals showed fewer side effects and seems to be as efficient as sulproston i.v. after cervical ripening.