Prognostic significance of UBE2C mRNA expression in high-risk early breast cancer. A Hellenic Cooperative Oncology Group (HeCOG) Study.

BACKGROUND: The ubiquitin-proteasome system (UPS) plays a pivotal role in tumorigenesis. Components of the UPS have recently been implicated in breast cancer progression. In the present study, we sought to explore the prognostic and/or predictive significance of UBE2C messenger RNA (mRNA) expression on disease-free survival (DFS) and overall survival (OS) in high-risk operable breast cancer patients. METHODS: Five hundred and ninety-five high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative, dose-dense sequential chemotherapy with epirubicin followed by CMF (cyclophosphamide, methotrexate and 5-fluorouracil) with or without paclitaxel (Taxol). RNA was extracted from 313 formalin-fixed primary tumor tissue samples followed by one-step quantitative RT-PCR for assessment of mRNA expression of UBE2C. RESULTS: High UBE2C mRNA expression was associated with poor DFS (Wald's P = 0.003) and OS (Wald's P = 0.005). High tumor grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of UBE2C. Results of the Cox multivariate regression analysis revealed that high UBE2C mRNA expression remained an independent adverse prognostic factor for relapse (P = 0.037) and death (P = 0.05). CONCLUSIONS: High UBE2C mRNA expression was found to be of adverse prognostic significance in high-risk breast cancer patients. These findings need to be validated in larger cohorts.

Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab.

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 (VEGF-1154, +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 VEGF-1154 GG genotype was more frequent in patients not responding to treatment compared with responders (65.5 versus 39.8%, P = 0.032). Furthermore, the VEGF-1154 GG genotype was associated with inferior median OS compared with GA (hazards ratio = 1.68; 95% confidence interval: 1.10-2.57; P = 0.016) or with the alternative genotypes (GA and AA) combined (hazards ratio = 1.62; 95% confidence interval: 1.09-2.40; P = 0.017). In multivariate analysis, the VEGF-1154 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.

Molecular markers in epithelial ovarian cancer: their role in prognosis and therapy.

Epithelial cancer of the ovary is the most lethal malignancy of all gynaecological cancers. Various clinical and pathological features of ovarian cancer are used as predictors of clinical outcome. The use of molecular markers in common clinical practice seems promising for the diagnosis and prognostication. The aim of this review article is to describe current theories regarding the pathogenesis and molecular evolution of epithelial ovarian cancer. With respect to the molecules involved, this article focuses on whether they are associated with poor prognosis or not. This evaluation is performed in light of the progress made and the potential usefulness in treatment decisions without overlooking existing controversies that should be further studied. It is tempting to anticipate the gradual integration of molecular profiling in clinical practice.

Solitary Colorectal Cancer Metastasis to the Pancreas.

INTRODUCTION: Secondary pancreatic metastasis from other solid organ malignancy is rare and accounts for less than 2% of all pancreatic tumors. The aim of this study is to highlight that colorectal metastatic disease in the pancreas could be in selected cases an indication for surgery rather than for palliative chemotherapy. CASE PRESENTATION: We present a case of a 62-year-old Caucasian female with a history of rectal adenocarcinoma. Four years ago, the patient underwent low anterior resection of the rectosigmoid, post neoadjuvant chemoradiotherapy, with adjuvant chemotherapy. During her follow-up, imaging examinations revealed a lesion in the pancreatic neck with features indicating primary pancreatic cancer. Near-total distal pancreatectomy with en bloc splenectomy was performed. Histopathology revealed metastatic disease compatible with colorectal adenocarcinoma as the primary cancer. Second-line chemotherapy was decided from the institutional tumor board. The patient remains disease free one year later. CONCLUSION: Pancreatic lesions in patients with a history of extrapancreatic malignancy should raise suspicions of metastatic disease. Surgical intervention is a legitimate treatment option for these pancreatic lesions, since they represent solitary disease deposits and of course in the context of multidisciplinary meeting decisions, and after proper and extensive staging investigations.