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Background: Cancer survivors are at risk of developing a second primary cancer (SPC) later in life because of persisting effects of genetic and behavioural risk factors, the long-term sequelae of chemotherapy, radiotherapy and the passage of time. This is the first study with Austrian data on an array of entities, estimating the risk of SPCs in a population-based study by calculating standardized incidence ratios (SIRs).Methods: This retrospective cohort study included all invasive incident cancer cases diagnosed within the years 1988 to 2005 being registered in the Tyrol and Vorarlberg Cancer Registries. Person years at risk (PYAR) were calculated from time of first diagnosis plus 2 months until the exit date, defined as the date of diagnosis of the SPC, date of death, or end of 2010, whichever came first. SIR for specific SPCs was calculated based on the risk of these patients for this specific cancer.Results: A total of 59,638 patients were diagnosed with cancer between 1988 and 2005 and 4949 SPCs were observed in 399,535 person-years of follow-up (median 5.7 years). Overall, neither males (SIR 0.90; 95% CI 0.86-0.93) nor females (SIR 1.00; 95% CI 0.96-1.05) had a significantly increased SIR of developing a SPC. The SIR for SPC decreased with age showing a SIR of 1.24 (95% CI 1.12-1.35) in the age group of 15-49 and a SIR of 0.85 (95% CI 0.82-0.89) in the age group of ≥ 65. If the site of the first primary cancer was head/neck/larynx cancer in males and females (SIR 1.88, 95% CI 1.67-2.11 and 1.74, 95% CI 1.30-2.28), cervix cancer in females (SIR 1.40, 95% CI 1.14-1.70), bladder cancer in males (SIR 1.20, 95% CI 1.07-1.34), kidney cancer in males and females (SIR 1.22, 95% 1.04-1.42 and 1.29, 95% CI 1.03-1.59), thyroid gland cancer in females (SIR 1.40, 95% CI 1.11-1.75), patients showed elevated SIR, developing a SPC.Conclusions: Survivors of head & neck, bladder/kidney, thyroid cancer and younger patients show elevated SIRs, developing a SPC. This has possible implications for surveillance strategies. [ABSTRACT FROM AUTHOR]

Background: An increasing body of evidence shows that miR-34 family has tumor suppressive properties mediating apoptosis, cell cycle arrest and senescence. In ovarian cancer, miR34 family members were found to be under expressed. Particularly miR-34a has been revealed to be a direct transcriptional target of p53 which is frequently mutated in epithelial ovarian carcinomas especially in high grade serous cancer. Moreover, methylation of miR-34a CpG Islands was found to down-regulate miR-34a expression. The aim of this study was to investigate the clinical relevance of mir34a as well as its promoter methylation in a subset of 133 ovarian cancers with a special focus on the p53 mutation status, the dualistic type I and type II ovarian cancer model and the different histotypes.Methods: One hundred thirty-three epithelial ovarian cancers and 8 samples of healthy ovarian surface epithelium were retrospectively analysed for miR-34a expression with quantitative real-time reverse transcription PCR (qRT-PCR). Gene-specific DNA methylation was evaluated with MethyLight technique.Results: Significantly lower miR-34a expression was found in ovarian cancers than in healthy ovarian epithelium (p = 0.002). The expression of miR-34a was found lower in type II than in type I cancers (p = 0.037), in p53 mutated as compared to p53 wild type cancers (p = 0.003) and in high grade compared to in low grade cancers (p = 0.028). In multivariate COX regression model low expressing miR-34a cancers exhibited a reduced PFS (p = 0.039) and OS (p = 0.018). In serous cancers low miR-34a levels showed a worse OS confirmed also in multivariate analysis (p = 0.022). miR-34a promoter methylation was found higher in type II cancers than in type I (p = 0.006). mir34a expression and promoter methylation showed an inverse correlation in cancer samples (p = 0.05).Conclusion: We demonstrated a clinical independent role of miR-34a in epithelial ovarian cancers. Moreover, we corroborated the correlation between miR-34a expression and its promoter methylation in a large set of ovarian cancers. The inverse association between miR-34a expression and grading, p53 mutation status and dualistic tumor type classification, together with its prognostic relevance may underline the tumor-suppressive character of miR-34a in ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Approximately one third of women diagnosed with ovarian cancer is 70 years or older. Information on the treatment reality of these elderly patients is limited. Methods: 275 patients with primary epithelial ovarian cancer FIGO stage II-IV undergoing cytoreductive surgery and platinum-based chemotherapy were prospectively included in this European multicenter study. Patients <70 and ⩾70 years were compared regarding clinicopathological variables and prognosis. Results: Median age was 58 years (18-85); 47 patients (17.1%) were 70 years or older. The postoperative 60-day -mortality rate was 2.1% for elderly and 0.4% for younger patients (p < 0.001). Elderly patients were less likely to receive optimal therapy (no residual disease after surgery and platinum combination chemotherapy) compared to patients <70 years (40.4% vs. 70.1%, p < 0.001) and their outcome was less favorable regarding median PFS (12 vs. 20 months, p = 0.022) and OS (30 vs. 64 months, p < 0.001). However, in multivariate analysis age itself was not a prognostic factor for PFS while the ECOG performance status had prognostic significance in elderly patients. Conclusions: Elderly patients with ovarian cancer are often treated less radically. Their outcome is impaired despite no consistent prognostic effect of age itself. Biological age and functional status should be considered before individualized treatment plans are defined. [ABSTRACT FROM AUTHOR]

Background: The immune system is a key player in fighting cancer. Thus, we sought to identify a molecular 'immune response signature' indicating the presence of epithelial ovarian cancer (EOC) and to combine this with a serum protein biomarker panel to increase the specificity and sensitivity for earlier detection of EOC. Methods: Comparing the expression of 32,000 genes in a leukocytes fraction from 44 EOC patients and 19 controls, three uncorrelated shrunken centroid models were selected, comprised of 7, 14, and 6 genes. A second selection step using RT-qPCR data and significance analysis of microarrays yielded 13 genes (AP2A1, B4GALT1, C1orf63, CCR2, CFP, DIS3, NEAT1, NOXA1, OSM, PAPOLG, PRIC285, ZNF419, and BC037918) which were finally used in 343 samples (90 healthy, six cystadenoma, eight low malignant potential tumor, 19 FIGO I/II, and 220 FIGO III/IV EOC patients). Using new 65 controls and 224 EOC patients (thereof 14 FIGO I/II) the abundances of six plasma proteins (MIF, prolactin, CA125, leptin, osteopondin, and IGF2) was determined and used in combination with the expression values from the 13 genes for diagnosis of EOC. Results: Combined diagnostic models using either each five gene expression and plasma protein abundance values or 13 gene expression and six plasma protein abundance values can discriminate controls from patients with EOC with Receiver Operator Characteristics Area Under the Curve values of 0.998 and bootstrap .632+ validated classification errors of 3.1% and 2.8%, respectively. The sensitivities were 97.8% and 95.6%, respectively, at a set specificity of 99.6%. Conclusions: The combination of gene expression and plasma protein based blood derived biomarkers in one diagnostic model increases the sensitivity and the specificity significantly. Such a diagnostic test may allow earlier diagnosis of epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Gene expression of peripheral myelin protein 22 (PMP22) and the epithelial membrane proteins (EMPs) was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study. We want to evaluate the prognostic impact of the expression of these genes on breast cancer. Methods: In a retrospective multicenter study, gene expression of PMP22 and the EMPs was measured in 249 primary breast tumors by real-time PCR. Results were statistically analyzed together with clinical data. Results: In univariable Cox regression analyses PMP22 and the EMPs were not associated with disease-free survival or tumor-related mortality. However, multivariable Cox regression revealed that patients with higher than median PMP22 gene expression have a 3.47 times higher risk to die of cancer compared to patients with equal values on clinical covariables but lower PMP22 expression. They also have a 1.77 times higher risk to relapse than those with lower PMP22 expression. The proportion of explained variation in overall survival due to PMP22 gene expression was 6.5% and thus PMP22 contributes equally to prognosis of overall survival as nodal status and estrogen receptor status. Cross validation demonstrates that 5-years survival rates can be refined by incorporating PMP22 into the prediction model. Conclusions: PMP22 gene expression is a novel independent prognostic factor for disease-free survival and overall survival for breast cancer patients. Including it into a model with established prognostic factors will increase the accuracy of prognosis. [ABSTRACT FROM AUTHOR]

Background: Gene expression of peripheral myelin protein 22 (PMP22) and the epithelial membrane proteins (EMPs) was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study. We want to evaluate the prognostic impact of the expression of these genes on breast cancer., Methods: In a retrospective multicenter study, gene expression of PMP22 and the EMPs was measured in 249 primary breast tumors by real-time PCR. Results were statistically analyzed together with clinical data., Results: In univariable Cox regression analyses PMP22 and the EMPs were not associated with disease-free survival or tumor-related mortality. However, multivariable Cox regression revealed that patients with higher than median PMP22 gene expression have a 3.47 times higher risk to die of cancer compared to patients with equal values on clinical covariables but lower PMP22 expression. They also have a 1.77 times higher risk to relapse than those with lower PMP22 expression. The proportion of explained variation in overall survival due to PMP22 gene expression was 6.5% and thus PMP22 contributes equally to prognosis of overall survival as nodal status and estrogen receptor status. Cross validation demonstrates that 5-years survival rates can be refined by incorporating PMP22 into the prediction model., Conclusions: PMP22 gene expression is a novel independent prognostic factor for disease-free survival and overall survival for breast cancer patients. Including it into a model with established prognostic factors will increase the accuracy of prognosis.

Background: To date, there is no consensus on the utility of screening procedures for the early detection of endometrial cancer. The value of transvaginal ultrasound for screening of asymptomatic endometrial cancer has been discussed controversially. This study was conducted to evaluate whether asymptomatic patients with endometrial cancer have a better prognosis than symptomatic patients with endometrial cancer diagnosed after postmenopausal bleeding., Methods: In the present multi-center study, the effect of the presence of postmenopausal bleeding on prognosis was evaluated retrospectively in 605 patients with endometrial cancer using patients' files. 543 patients (133 patients were asymptomatic, 410 patients were symptomatic) with endometrioid endometrial cancer were enrolled in all further analysis. Student's t-test, Cox regression analysis and Kaplan-Meier analysis were used were appropriate., Results: Presence/absence of a postmenopausal bleeding was not associated with tumor stage (p = 0.2) and age at diagnosis (p = 0.5). Asymptomatic patients with endometrial cancer had a significantly higher rate of well and moderate-differentiated tumors compared to symptomatic patients (p = 0.008). In univariable and multivariable survival analysis, tumor stage, tumor grade, and patients' age at diagnosis, but not presence/absence of a postmenopausal bleeding, were associated with disease free and overall survival., Conclusion: Asymptomatic patients with endometrial cancer have a higher rate of well differentiated tumors compared to patients with a postmenopausal bleeding prior to diagnosis. The prognosis of both groups of patients was similar.