K Friese

Ultrasonographic detection of asymptomatic endometrial cancer in postmenopausal patients offers no prognostic advantage over symptomatic disease discovered by uterine bleeding

The aim of this study was to investigate whether endometrial carcinoma (EC) screening by transvaginal sonography (TVS) has a prognostic advantage over symptomatic EC. In a retrospective study, 190 postmenopausal patients with symptomatic EC and 123 asymptomatic patients with suspicious endometrium detected by TVS were analysed regarding clinical, socio-economic and histopathological findings. Total bleeding time and the International Federation of Gynecology and Obstetrics (FIGO) tumour stage were evaluated with respect to their effect on survival. In 123 asymptomatic patients with suspicious endometrium, 16 (13%) EC, 61 (50%) polyps, 21 (17%) hyperplasias, 23 (19%) atrophias, 1 (0.8%) myoma and 1 (0.8%) metastasis were found. TVS findings in asymptomatic patients resulted in unnecessary operations, which were associated with considerable costs totalling at least 116256. Compared with screened asymptomatic patients, symptomatic patients were significantly (P<0.05) older, more frequently obese, and hypertensive, had a larger proportion of cases living in rural areas and visited their gynaecologists rarely. The bleeding time of symptomatic patients strongly correlated with the tumour stage (P<0.0001). Depending on the bleeding time, the 5-year disease-free survival and overall survival rates were 77% and 86% (no bleeding), 83% and 98% (<8 weeks), 74% and 90% (8-16 weeks), and 62% and 69% (>16 weeks), respectively. The corresponding tumour stage-related data for disease-free and overall survival were 100% (Ia; both rates), 87% and 95% (Ib), 66% and 93% (Ic), 63% and 78% (II) and 36% (III/IV; both rates), respectively. Postmenopausal vaginal bleeding represents an early symptom of EC, but it is not always perceived as problematic by the patients. There is no prognostic advantage for screened compared with symptomatic patients, who had bleeding of shorter than 8 weeks. Moreover, patients who are at a high risk for EC tend to avoid TVS screening. Finally, endometrial screening often results in unnecessary operations, which are associated with increased morbidity and costs.

Expression of the apoptosis-inducing ligands FasL and TRAIL in malignant and benign human breast tumors

Abstract Apoptosis-inducing ligands such as Fas ligand (FasL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been found to play an important role in cell regulation. Different malignant tumors show an altered expression of these ligands and their respective receptors compared to normal tissues. The purpose of this study was therefore to investigate expression of TRAIL, FasL, and its receptor Fas on protein and mRNA levels in breast carcinomas (n=40), fibroadenomas (n=7), and normal breast tissues (n=5). Immunohistochemical reaction demonstrated that FasL was strongly expressed in breast cancer tissues (34/40) while only one fibroadenoma and one normal breast tissue reacted weakly positive for FasL. All fibroadenomas and normal breast tissues as well as the majority of breast cancer tissues expressed Fas on protein level. Quantitative RT-PCR analysis detected high expression of FasL mRNA in breast cancer tissues and fibroadenomas, whereas fibroadenomas showed the highest Fas mRNA copy numbers, followed by breast cancer tissues and normal breast tissues (P<0.05). Compared to FasL expression, TRAIL could be detected in less breast cancer tissues on protein level (21/40) and was found in only one fibroadenoma and none of the normal breast tissues. Thus, it can be concluded that malignant breast tumors show an altered expression of the two apoptosis-inducing ligands FasL and TRAIL.

The role of infection in preterm labour

Although there are many maternal characteristics associated with preterm birth, the aetiology in most cases is poorly understood. Our research demonstrates that multiple risk factors, such as maternal age and especially infection, are associated with preterm birth. Bacterial vaginosis and intrauterine infection are now believed to be an important risk factor for preterm delivery.

Tumour Fas ligand:Fas ratio greater than 1 is an independent marker of relative resistance to tamoxifen therapy in hormone receptor positive breast cancer

BackgroundThe objective of the present study was to examine the prognostic and predictive significance of the apoptosis-related marker Fas ligand (FasL):Fas ratio in breast cancer.MethodsTumour biopsies from 215 primary invasive breast cancer patients were examined for the expression of FasL and Fas mRNA transcripts by quantitative real-time RT-PCR. Their prognostic and predictive impact on patient survival was determined in univariate and multivariate survival analyses.ResultsUsing a cutoff value of 1, a FasL:Fas ratio greater than 1 was found to have significant prognostic value for disease-free survival among the total population (median follow up 54 months). It was associated with a significantly decreased disease-free survival (P = 0.022) and with a tendency toward increased mortality (P = 0.14) in univariate analysis. Hormone receptor positive women exclusively treated with tamoxifen (n = 86) and with a FasL:Fas ratio greater than 1 had a significantly decreased disease-free survival (P = 0.008) and overall survival (P = 0.03) in univariate Kaplan–Meier analysis. Furthermore, tumour size and FasL:Fas ratio were of independent predictive significance in the multivariate model for disease-free and overall survival in that subgroup. Among postmenopausal patients (n = 148) both of those factors retained independent prognostic significance in the multivariate model for disease-free survival. In contrast, FasL:Fas ratio had no significant predictive value in patients exclusively treated with chemotherapy.ConclusionThe data presented indicate that FasL:Fas ratio may be useful not only as a prognostic factor but also as a predictive factor for projecting response to the antioestrogen tamoxifen. The results strongly support a correlation between FasL:Fas ratio greater than 1 and lack of efficacy of tamoxifen in hormone receptor positive patients.

Absolute quantification of human chorionic gonadotropin-β mRNA with TaqMan™ detection

We describe a reverse transcriptase-polymerase chain reaction (RT-PCR) for determination of human chorionic gonadotropin-β (HCGβ) mRNA copies using the TaqMan™ system. To evaluate our quantitative assay, we analyzed HCGβ transcripts of all protein coding genes (HCGβ 5, 3, 8, and 7) in human RNA panels of different normal tissues and in glycodelin-A-stimulated trophoblast cell cultures. Absolute quantification using HCGβ TaqMan probe was found to be highly reproducible. Our study of RNA panels confirms recently published results that expression of HCGβ transcripts is a common feature of a great variety of different normal tissues. High levels of HCGβ mRNAs (>1.000 molecules per 200 ng RNA) were detected in placenta, uterus, and testis. An increase of HCGβ mRNA expression (1.7-fold) was detected at 150 µg/mL glycodelin-A treatment in trophoblast cell culture. Time-dependence study showed that the increase in HCGβ mRNA level was evident at 60 min after glycodelin-A treatment. In summary, we have developed a highly sensitive one-tube, one-enzyme quantitative RT-PCR system that is time-saving and avoids postamplification procedures.

Interleukin-6 receptor is highly expressed in the ganglionic eminence of the human fetal brain.

The expression of interleukin-6 receptor (IL-6R) has been investigated immunohistochemically in seven fetal brains with special reference to the ganglionic eminence (GE), a part of the telencephalic proliferative zone. Between the 22nd and 28th gestational week the GE stands out conspicuously due to its very high amount of intensely IL-6R-immunostained cells. Adjacent brain areas exhibit only very weak immunoreactivity. Between the 32nd and 36th week a moderate IL-6R immunolabelling is seen in the remnants of the GE. IL-6 may activate the immature IL-6R-positive cells to secrete a protease which is likely to be involved in GE involution and, perhaps, in the development of hemorrhage frequently occurring in the GE of premature infants.

Differential diagnosis of peri- and postmenopausal ovarian cysts.

OBJECTIVES To test the value of preoperative and intracystic parameters in the differential diagnosis of ovarian cysts. METHODS Criteria for admission of 58 patients were age > 47 years, complete history, detection of CA 125 serum level, and ultrasound findings. Tumor markers (CA 125, cancer-associated serum antigen (CASA), CA 72-4), hormones (estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH)), epidermal growth factor (EGF) receptor and c-erb B-2 amplification rate were detected in cyst fluid. RESULTS Of the 58 subjects, 9 (15.4%) had functional cysts, 37 (63.8%) had benign tumors and 12 (20.8%) had malignant tumors. No functional ovarian cyst presented as echoic or multilocular cyst sonographically. The serum CA 125 values demonstrated significant differences between the non-malignant and malignant patient groups (P < 0.0005). The majority (63.8%, n = 37) of ovarian cysts were obtained at laparotomy, whereas only 36.2% (n = 21) were laparoscopically operated. The cyst fluid levels of FSH (P < 0.005) and LH (P < 0.05) were significantly lower in the functional group than in the benign or malignant group. Malignant cysts were significantly different from non-malignant cysts regarding low E2 (P < 0.01), high FSH (P < 0.05) and CASA (P < 0.02) values. There were no significant correlations between EGF receptor (P = 0.14) and c-erb B-2 (P = 0.06) gene amplification rates and malignant histology. CONCLUSIONS Simple ovarian cysts combined with normal serum CA 125 levels are candidates for conservative follow-up or laparoscopy. The serum CA 125 is a powerful marker for prediction of histology in postmenopausal ovarian cyst. Laparoscopic surgery may be considered in patients with multilocular sonographic findings and normal CA 125 serum level. Combining serum CA 125 levels with cyst fluid parameters (E2, FSH, CASA) improves the sensitivity and specificity in predicting malignancy.

Treatment of pregnancy associated gynaecological malignancies

Pregnancy, leading to new life, on one hand, and life threatening malignancies an the other hand, are per se diametric subjects. Symptoms of malignancies are ignored more frequently during pregnancy by patients and physicians, often resulting in delayed diagnosis. Diagnosis and treatment of gynaecological malignancies, however, are increasingly important for four reasons: the peak incidence of several malignancies occurs during the reproductive age; late pregnancies present more often in an age group with increased risk for cancer, intensified care for pregnant women leads to more thorough diagnosis, and, curative treatment of malignancies gives women the potential chance for becoming pregnant. For these reasons, special features of the diagnosis and treatment of gynaecological malignancies will regularly part of routine patient care. This review article covers certain practice related features of gynaecological malignancies.

Clinical Evaluation of Mucin-1 (MUC1) and P16 in Laryngeal Cancer

Background: Adapted from results in the field of cervical cancer, a direct connection between HPV infection and oropharyngeal carcinoma development could be established. Aim of this study was to evaluate p16 and TA-MUC1 in laryngeal cancer and their correlation to diagnostic, since TA-MUC1 is primarily restricted to malignancies. Methods: Paraffin-embedded laryngeal cancer specimens (n=129) and normal tissue (n=5) were analyzed for TA-MUC1 expression using hPankoMab-GEXTM antibody and evaluated according the immunoreactive score. Survival was assessed via log-rank test and Kaplan-Meier-survival analysis. Results: Significant correlation with tumor grading and staging was exhibited by TA-MUC1staining, while being negative in normal tissues. Expression of p16 significantly increased in T4 compared to T1 tumors. Significant differences in overall survival were found in correlation to TNM-classification, grading and relapse. TA-MUC1 showed a positive trend correlating to p16. Conclusion: Because of this positive trend, we suggest a HPV association in head and neck tumors. Most likely due to an insufficient quantity of HPV-positive patients, no statistical significance could be established. However, targeting TA-MUC1 would improve tumor therapy by linking hPankoMab-GEXTM to the overexpressed galectin. Systematic analysis of HPV-association should be performed generally in laryngeal cancer to gain further information about the interaction of HPV and malignancies.

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