Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients.

BACKGROUND: Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient's serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15-3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15-3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival. METHODS: Patients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15-3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0. RESULTS: Serum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15-3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p< 0.001) than in patients with benign disease.Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression. CONCLUSIONS: This study found significantly elevated Mucin-1 serum concentrations in ovarian carcinoma patients as compared to those women suffering from benign ovarian diseases. However, it needs to be noted that Mucin-1 concentrations in carcinoma patients showed a rather high variability. Results from immunohistochemistry indicate that Mucin-1 has a prognostic relevance in ovarian carcinomas when evaluating the expression by VU4H5 antibody.

Lack of prognostic relevance of Her-2/neu, topoisomerase IIα and EGFR in advanced ovarian carcinoma.

Patients with advanced ovarian cancer (FIGO stage III) have a poor clinical prognosis. However, these patients show distinct differences in their survival time, possibly due to differing responses to chemotherapy and differing tumor biology. In contrast to histological subtype, grading and staging, which are known to affect a patient's prognosis, the impact of the human epidermal growth factor receptor 2 (Her-2/neu), topoisomerase IIα and epidermal growth factor receptor (EGFR) on survival remain inconclusive. Therefore, the aim of this study was to assess their impact on survival in a group of advanced ovarian cancer patients. Tissue microarrays were constructed from specimens of 243 patients. Gene copy and chromosome numbers were evaluated by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry (IHC). Scoring for the latter was calculated by considering the percentage of positive tumor cells and the relative staining intensity. FISH results were evaluated by previously published recommendations and correlated with overall survival. Using IHC, 1.6% of the cases that were tested for Her-2/neu and topoisomerase IIα were strongly positive, and 12.3% were positive for EGFR. Using FISH, 4.4% amplifications and 2.1% polysomies for Her-2/neu were identified; topoisomerase IIα showed 2.2% amplifications, 0.4% deletions and 3.5% polysomies. We observed 10.8% high polysomies, but no amplification for EGFR. None of the results obtained by IHC or FISH correlated with overall survival. In general, Her-2/neu, topoisomerase IIα and EGFR may be prognostic factors in ovarian carcinomas. However, within this group of FIGO stage III patients, differences in gene aberration or protein expression were not able to predict differences in survival.

Her-2/neu and topoisomerase IIα in advanced breast cancer: a comprehensive FISH analysis of 245 cases.

Her-2/neu gene amplification is an established prognostic factor in breast cancer, and Her-2/neu protein is the target of the therapeutic monoclonal antibody Herceptin. More recently, topoisomerase IIα became a new focus of breast cancer research because of its role as a target for anthracycline therapy. Therefore, we compared Her-2/neu and topoisomerase IIα amplification/deletion in a large series of advanced breast cancer using fluorescence in situ hybridization. Paraffin-embedded archival tissue from 245 patients was retrieved and assessed for Her-2/neu and topoisomerase IIα amplification/deletion by fluorescence in situ hybridization according to standard protocols. Relation to clinical data and survival was sought. A total of 245 cases were analyzed. Amplification for Her-2/neu was seen in 57 cases (23.3%), and for topoisomerase IIα in 12 cases (4.9%). Coamplification was found in 9 samples (3.7%), 3 cases (1.2%) showed amplification of topoisomerase IIα but not of Her-2/neu, and 48 samples (19.8%) displayed amplification for Her-2/neu but not for topoisomerase IIα. Correlation to the histologic type, the stage, or the grade could not be found. Only the amplification of topoisomerase IIα was associated with very poor outcome; survival of cases with amplification of Her-2/neu only was slightly lower than the mean overall survival (27.4 vs. 31.9 mo). Amplification of Her-2/neu and/or topoisomerase IIα is associated with poor overall survival. Amplification of topoisomerase IIα does not seem to be necessarily linked to Her-2/neu-amplification. However, independent determination of these 2 markers seems to be valuable for an individualized therapy of breast cancer patients.

Clinical characteristics and outcomes of BRCA-associated ovarian cancer: genotype and survival.

Previous studies have suggested that BRCA-related epithelial ovarian cancer (EOC) conveys improved survival compared with that of sporadic EOC, but few studies have evaluated differences between BRCA genotypes. We compared characteristics and outcome by genotype in BRCA-associated EOC. Patients with BRCA-associated EOC who were diagnosed between January 30,1981, and December 30, 2008, were retrospectively identified through institutional review board-approved registry studies. We examined clinical characteristics, including event-free survival (EFS) and overall survival (OS), for BRCA1 versus BRCA2 patients. We identified 197 cases (148 BRCA1 cases; 49 BRCA2 cases); the median follow-up period was 63 months. BRCA2 patients were older (55.4 vs. 51.1 y; P < 0.01) and had fewer poorly differentiated tumors (67% vs. 82%; P < 0.05). No difference in EFS was observed. OS at 5 years was 75% in BRCA2 patients versus 61% in BRCA1 patients; this was not statistically significant. A non-significant trend toward improved OS was observed in BRCA2 patients with advanced-stage disease (hazard ratio = 0.59; 95% confidence interval 0.32-1.08). Age and grade differed significantly between BRCA1 and BRCA2 carriers in our study population. Whereas no overall differences in EFS or OS were observed, there was a trend toward improved OS in BRCA2 carriers with advanced-stage disease. This may reflect important differences between BRCA genotypes and should be validated in larger studies.

Lower genital tract metastases at time of first diagnosis of mammary invasive lobular carcinoma.

INTRODUCTION: Although breast cancer is a major health problem worldwide, metastatic disease to the lower genital tract remains to be a rare event. CASE REPORT: A 64-year old woman was admitted to our hospital due to newly diagnosed ascites and peripheral edema. A computer tomography had shown peritoneal carcinosis but no clear evidence of an intraabdominal mass. CA 12-5 levels were elevated. Physical examination of the breast did not show any abnormal findings, except for the fact that the patient was post bilateral breast augmentation in 1999. The peritoneal carcinosis was thought to originate from the ovaries or the endometrium and therefore the patient underwent a laparotomy with hysterectomy, bilateral salpingoovariectomy and omentectomy. Histological findings revealed a low differentiated adenocarcinoma, most likely originating from primary breast cancer. A bilateral mammography was suspicious of a tumour in the left breast which was confirmed in a second surgery. Histology showed a moderately differentiated invasive-lobular breast cancer. CONCLUSION: To our knowledge, this is the first report about metastasis to the lower genital tract on initial presentation of an invasive-lobular carcinoma. In the differential diagnosis of peritoneal carcinosis, metastases of an invasive-lobular carcinoma should be considered.