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Ymittos Athens, Greece

Fostira F.,National Diagnostics | Thodi G.,National Diagnostics | Sandaltzopoulos R.,Democritus University of Thrace | Fountzilas G.,Aristotle University of Thessaloniki | And 2 more authors.
BMC Cancer | Year: 2010

Background: Familial adenomatous polyposis, an autosomal dominant inherited disease caused by germline mutations within the APC gene, is characterized by early onset colorectal cancer as a consequence of the intrinsic phenotypic feature of multiple colorectal adenomatic polyps. The genetic investigation of Greek adenomatous polyposis families was performed in respects to APC and MUTYH germline mutations. Additionally, all available published mutations were considered in order to define the APC mutation spectrum in Greece.Methods: A cohort of 25 unrelated adenomatous polyposis families of Greek origin has been selected. Genetic testing included direct sequencing of APC and MUTYH genes. APC gene was also checked for large genomic rearrangements by MLPA.Results: Analysis of the APC gene performed in a Greek cohort of twenty five FAP families revealed eighteen different germline mutations in twenty families (80%), four of which novel. Mutations were scattered between exon 3 and codon 1503 of exon 15, while no large genomic rearrangements were identified.Conclusion: This concise report describes the spectrum of all APC mutations identified in Greek FAP families, including four novel mutations. It is concluded that the Greek population is characterized by genetic heterogeneity, low incidence of genomic rearrangements in APC gene and lack of founder mutation in FAP syndrome. © 2010 Fostira et al; licensee BioMed Central Ltd.

Koutras A.K.,University of Patras | Fountzilas G.,Aristotle University of Thessaloniki | Kalogeras K.T.,Aristotle University of Thessaloniki | Kalogeras K.T.,Hellenic Cooperative Oncology Group | And 3 more authors.
Critical Reviews in Oncology/Hematology | Year: 2010

The human epidermal growth factor receptor (HER) family comprises four homologous members. The activation of these receptors affects essential tumorigenic processes and plays a crucial role in the pathogenesis of breast cancer. Among HER family members, EGFR and HER2 are the most studied. However, accumulating data provide evidence for the significance of HER3 and HER4 alterations in breast carcinogenesis. The combination of HER2 and HER3 receptors may be critical in breast cancer growth and progression. Moreover, HER3 may provide a route for resistance to agents targeting EGFR or HER2. Although a number of studies have demonstrated that HER3 overexpression is associated with poor prognosis in patients with breast cancer, other studies have indicated that HER3 overexpression may be a positive prognostic factor. With respect to HER4 receptor, the existing evidence suggests that HER4 signalling promotes differentiation and growth inhibition of breast cancer cells. In addition, HER4 is more consistently related with a favourable prognosis in breast cancer. HER4 has multiple different activities in the breast, and many of these functions are mediated by a soluble HER4 intracellular domain. In addition, loss of HER4 expression may represent a marker for resistance to tamoxifen. Because of the functional interdependency among the HER receptors, it is possible that the effect on cell proliferation and tumor growth depends on receptor trans-signalling. Therefore, clarifying how and the extent to which these different signalling pathways interact in breast carcinogenesis, may lead to additional therapeutic opportunities. This review presents an update on the role of HER3 and HER4 receptors in breast cancer. Moreover, we provide current data relating to the prognostic significance of these receptors, as well as their impact on the activity of HER-targeting therapies in patients with breast cancer. © 2009 Elsevier Ireland Ltd.

Lakis S.,Aristotle University of Thessaloniki | Kotoula V.,Aristotle University of Thessaloniki | Eleftheraki A.G.,Hellenic Cooperative Oncology Group | Batistatou A.,University of Ioannina | And 9 more authors.
Breast | Year: 2014

The Androgen Receptor (AR) is a potential prognostic marker and therapeutic target in breast cancer. We evaluated AR protein expression in high-risk breast cancer treated in the adjuvant setting. Tumors were subtyped into luminal (ER+/PgR±/AR±), molecular apocrine (MAC, [ER-/PgR-/AR+]) and hormone receptor negative carcinomas (HR-negative, [ER-/PgR-/AR-]). Subtyping was evaluated with respect to prognosis and to taxane therapy. High histologic grade (p<0.001) and increased proliferation (p=0.001) more often appeared in MAC and HR-negative than in luminal tumors. Patients with MAC had outcome comparable to the luminal group, while patients with HR-negative disease had increased risk for relapse and death. MAC outcome was favorable upon taxane-containing treatment; this remained significant upon multivariate analysis for overall survival (HR 0.31, 95%CI 0.13-0.74, interaction p=0.035) and as a trend for time to relapse (p=0.15). In conclusion, AR-related subtyping of breast cancer may be prognostic and serve for selecting optimal treatment combinations. © 2014 Elsevier Ltd.

Koutras A.K.,University of Patras | Antonacopoulou A.G.,University of Patras | Eleftheraki A.G.,Hellenic Cooperative Oncology Group | Dimitrakopoulos F.-I.,University of Patras | And 14 more authors.
Pharmacogenomics Journal | Year: 2012

The aim of the study was to evaluate the association of vascular endothelial growth factor (VEGF) genotypes with treatment efficacy in a randomized trial. This study compared two chemotherapy regimens (FOLFIRI versus XELIRI) combined with bevacizumab, as first-line treatment for metastatic colorectal cancer. DNA was extracted from blood samples of 173 patients participating in the trial. Genotyping was performed for selected SNPs (VEGF1154, 936, 634, 2578 and 1498). All candidate genotypes were evaluated for associations with overall survival (OS), progression-free survival (PFS) and response rate (RR). There were no significant differences with respect to the distribution of genotypes in the treatment groups. The VEGF1154 GG genotype was more frequent in patients not responding to treatment compared with responders (65.5 versus 39.8%, P0.032). Furthermore, the VEGF1154 GG genotype was associated with inferior median OS compared with GA (hazards ratio1.68; 95% confidence interval: 1.10-2.57; P0.016) or with the alternative genotypes (GA and AA) combined (hazards ratio1.62; 95% confidence interval: 1.09-2.40; P0.017). In multivariate analysis, the VEGF1154 GG genotype remained a significant adverse factor for OS. Our results support the potential predictive ability of VEGF genotypes in patients with metastatic colorectal cancer receiving irinotecan-based chemotherapy plus bevacizumab, in terms of RR and OS. However, current results should be validated prospectively, in larger cohorts. © 2012 Macmillan Publishers Limited.

Lazaridis G.,Aristotle University of Thessaloniki | Lambaki S.,Aristotle University of Thessaloniki | Karayannopoulou G.,Aristotle University of Thessaloniki | Eleftheraki A.G.,Hellenic Cooperative Oncology Group | And 6 more authors.
Strahlentherapie und Onkologie | Year: 2014

Background and purpose. There are scarce data available on the prognostic/predictive value of p-Akt and p-mTOR protein expression in patients with high-risk early breast cancer. Patients and methods. Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 997 patients participating in two adjuvant phase III trials were assessed for EGFR, PTEN, p-Akt, p-mTOR protein expression, and PIK3CA mutational status. These markers were evaluated for associations with each other and with selected patient and tumor characteristics, immunohistochemical subtypes, disease-free survival (DFS), and overall survival (OS). Results. p-mTOR protein expression was negatively associated with EGFR and positively associated with PTEN, with p-Akt473, and with the presence of PIK3CA mutations. EGFR expression was positively associated with p-Akt473, p-Akt308, and PIK3CA wild-type tumors. Finally, p-Akt308 was positively associated with p-Akt473 expression. In univariate analysis, EGFR (p=0.016) and the coexpression of EGFR and p-mTOR (p=0.015) were associated with poor OS. Among patients with p-Akt308-negative or low-expressing tumors, those treated with hormonal therapy were associated with decreased risk for both relapse and death (p=0.013 and p<0.001, respectively). In the subgroup of patients with locoregional relapse, positive EGFR and mTOR protein expression was found to be associated with increased (p=0.034) and decreased (p<0.001) risk for earlier relapse, respectively. In multivariate analysis, low levels of p-Akt308 and the coexpression of EGFR and p-mTOR retained their prognostic value. Conclusion. Low protein expression of p-Akt308 was associated with improved DFS and OS among patients treated with hormonal therapy following adjuvant chemotherapy. Coexpression of EGFR and p-mTOR was associated with worse OS. © 2014 Springer-Verlag.

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