A concept of a MIABIS based register of biosample collections at the Medical University of Innsbruck.

The knowledge about the quality of samples and associated clinical data in biospecimen collections is a premise of clinical research. An electronic biosample register aims to facilitate the discovery of information about biosample collections in a hospital. Moreover, it might improve scientific collaboration and research quality through a shared access to harmonized sample collection description data. The aim of this paper is to present a concept of a web-based biosample register of the existing biosample collections at the Medical University of Innsbruck. A uniform description model is built based on an analysis of the sample collection data of independent sample management systems from two departments within the hospital. An extended set of attributes of the minimum dataset used by the Swedish sample collection register (MIABIS) has been applied to all biosample collections as a common description model. The results of the analysis and the data model are presented together with a first concept of a sample collection search register.

Significant survival impact of MACC1 polymorphisms in HER2 positive breast cancer patients.

BACKGROUND: Deregulation of hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signalling has been associated with poor clinical outcome in breast cancer and other cancers. The recently discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Potential links between genetic variants of the MACC1 gene and survival in breast cancer patients are unknown. In the present study, we therefore aimed to investigate the influence of MACC1 polymorphisms on event-free and overall survival in patients with human epidermal growth factor 2 (HER2)-positive breast cancer. METHODS: The present study included 164 consecutive white patients with HER2-positive breast cancer. Three MACC1 polymorphisms, rs1990172, rs975263 and rs3735615, already associated with cancer prognosis or with potential functional effects, were genotyped by the 5' nuclease assay. RESULTS: Multivariate Cox regression analysis adjusted for age and tumour stage showed increased risk for progression or death for carriers of the rare allele (G-allele) of single nucleotide polymorphism (SNP) rs1990172 (hazard ratios (HR) = 2.26; p = 0.004 and HR = 3.13; p = 0.001 for event-free survival and overall survival, respectively). In addition, we were able to demonstrate an adverse effect on cancer prognosis for carriers of the rare allele (T-allele) of SNP rs975263 (HR = 2.17; p = 0.007 and HR = 2.80; p = 0.003 for event-free survival and overall survival, respectively). The rare allele (C-allele) of SNP rs3735615 showed a significant protective impact on event-free survival as well as overall survival (HR = 0.25; p = 0.001, and HR = 0.16; p = 0.001, respectively). CONCLUSIONS: This study provides first evidence that MACC1 polymorphisms are associated with clinical outcome for HER2-positive breast cancer patients. Further studies are warranted to validate these findings.

Association of a common genetic variant of the IGF-1 gene with event-free survival in patients with HER2-positive breast cancer.

PURPOSE: Insulin-like growth factor 1 (IGF-1) stimulates mitosis and inhibits apoptosis. High circulating IGF-1 levels are linked with an increased risk of colorectal and breast cancer. Recently, IGF-1 single nucleotide polymorphisms (SNPs), especially variant rs2946834, have been associated with poor clinical outcome in patients with colorectal cancer. In the present study, we aimed to investigate the influence of IGF1 polymorphisms associated with IGF-1 plasma levels on event-free survival in patients with HER2-positive breast cancer. METHODS: The present study included 161 consecutive white patients with HER2-positive breast cancer. Event-free survival was calculated as the time from cancer diagnosis to either relapse or death from any cause. Genomic DNA was extracted from archived formalin-fixed paraffin-embedded tumor tissue samples; five IGF-1 polymorphisms (rs2946834, rs6220, rs1520220, rs5742694, and rs5742678), all associated with IGF-1 levels, were genotyped by SNaPshot assays. RESULTS: Kaplan-Meier analysis showed a poorer clinical outcome for carriers of the rare allele of SNP rs2946834 (log-rank test, p = 0.020). Concordantly, in univariate Cox regression analyses, the rare allele of SNP rs2946834 was significantly associated with a decreased event-free survival (HR = 3.06 [1.14-8.22]; p = 0.027). Multivariate analysis adjusted for age and tumor stage confirmed this result (HR = 4.02 [1.36-11.90]; p = 0.012). Other investigated polymorphisms of the IGF1 gene were not significantly associated with event-free survival (all p values >0.05). CONCLUSIONS: This study provides first evidence that IGF1 rs2946834 polymorphism is associated with clinical outcome of HER2-positive breast cancer patients. Further studies are warranted to validate these findings.

MDM2 SNP309 modifies the prognostic significance of the p53 mutational status in patients with ovarian cancer.

A single nucleotide polymorphism (SNP309) of MDM2 causes elevated MDM2 levels and an attenuation of p53 function. The aim of the present study was to examine the clinical relevance of the MDM2 SNP309 in ovarian cancer.MDM2 SNP309 genotype was analyzed in 198 patients with primary ovarian cancer. MDM2 expression was investigated using immunohistochemistry. A functional yeast-based assay and subsequent sequencing were performed to determine p53 mutational status. Of the patients, 44.4% (88 of 198) exhibited the common variant (T/T), 40.9% (81 of 198) the heterozygous variant (T/G) and 14.7% (29 of 198) the homozygous variant (G/G) MDM2 SNP309 genotype. MDM2 SNP309 was not associated with p53 mutational status, MDM2 expression, clinicopathological parameters or prognosis. In patients with the T allele (T/T and T/G genotype), p53 wild type carcinomas were associated with significantly improved recurrence-free (p<0.001) and overall survival (p<0.001) as compared to p53 mutant carcinomas. In contrast, p53 mutational status did not possess prognostic relevance in G/G carriers. A possible functional impairment of the p53 pathway caused by the G/G genotype of the MDM2 SNP309 may modify the association between p53 mutational status and prognosis in ovarian cancer.

Clinical relevance of TAp73 and ΔNp73 protein expression in ovarian cancer: a series of 83 cases and review of the literature.

The p73 gene gives rise to the full-length transactivation competent TAp73 and the N-terminally truncated isoform ΔNp73, which inhibits TAp73 and wild-type p53. The clinical relevance of TAp73 and ΔNp73 protein expression has not yet been evaluated in ovarian cancer. TAp73 and ΔNp73 expression was examined using immunohistochemistry and reverse transcription-polymerase chain reaction in 83 and 64 ovarian cancer specimens, respectively. A yeast-based assay and subsequent sequencing were performed to analyze the p53 mutational status. TAp73 and ΔNp73 protein expression was found in 73 of 83 (88%) and 48 of 83 (57.8%) ovarian cancer samples, respectively. The majority of cases showed immunostaining in both the nucleus and cytoplasm of tumor cells. TAp73 and ΔNp73 protein expression correlated with messenger RNA quantification in 25 of 64 (39.1%) and 37 of 64 (57.8%) cancer specimens, respectively. TAp73 and ΔNp73 protein expression was not associated with the p53 mutational status, clinicopathologic parameters, and prognosis of the examined ovarian cancer cases. Although TAp73 and ΔNp73 protein expression did not possess prognostic significance for ovarian cancer in this study, a potential clinical role of p73 isoforms cannot be definitively excluded due to limitations of immunohistochemistry.

Activated p38-MAPK and gemcitabine sensitivity in recurrent ovarian cancer.

BACKGROUND: Our study aimed to investigate if p38-MAPK determined in primary ovarian cancer can serve as a predictive marker for sensitivity to gemcitabine treatment in recurrent disease. MATERIALS AND METHODS: Activated (phosphorylated) p38-MAPK was immunohistochemically assessed in paraffin-embedded tumors obtained at primary debulking surgery from 45 patients treated with gemcitabine for platinum-resistant recurrence. The value of activated p38-MAPK in predicting sensitivity to gemcitabine treatment was statistically evaluated. RESULTS: Activated p38-MAPK was demonstrated in all healthy ovaries and all ovarian carcinomas examined. In controls, the median histological score (H-score) for activated p38-MAPK staining was 200, while in ovarian cancer the median H-score was 100. Activity of p38-MAPK in ovarian cancer tissue was not associated with overall response or survival after gemcitabine chemotherapy. CONCLUSION: P38-MAPK activity, determined by immunohistochemistry in ovarian cancer specimens obtained at primary diagnosis, cannot serve as a predictive marker for sensitivity to gemcitabine treatment in platinum-resistant disease.