Wnt pathway signaling is crucial in many cancers and data indicate crosstalk with other key cancer pathways, however in urothelial carcinogenesis it has not been extensively studied. We searched for mutations in adenomatous polyposis coli (APC), a key regulator of the pathway, and studied b-catenin expression and interactions with the expression of other markers of apoptosis, angiogenesis, and proliferation in patients with invasive urothelial cancer. The mutation cluster region of APC was directly sequenced in 70 patients with muscle invasive disease who were treated with surgery and adjuvant chemotherapy. COX-2, p53, Ki67, and b-catenin were studied immunohistochemically and micro vessel density was quantified by CD105 expression. Single somatic amino-acid substitutions (missense) were found in 9 (13%) and frameshift deletions in 2 (3%) tumors, all located in regions adjacent to b-catenin binding sites. Patients having either APC missense mutations or b-catenin nuclear accumulation had less frequent COX-2 overexpression (24% vs. 76%, p 5 0.043) and more frequent lymph node involvement (75% vs. 38%, p 5 0.023). Patients with either APC mutations or b-catenin accumulation had shorter disease-free interval (13.4 vs. 28 months, p 5 0.07), whereas in multivariate analysis they had shorter diseasespecific survival (60.5 vs. 20.6 months, p 5 0.048). Somatic APC missense mutations are not rare in advanced urothelial neoplasms. Either APC mutations and/or aberrant expression of b-catenin are associated with worse outcome. Further study of the role of the Wnt pathway, potential crosstalk with other pathways and potential candidate therapeutic targets in urothelial cancer is needed. '

Introduction Parietal cell/oncocytic gastric carcinomas are very rare and various aspects of this group remain unclear. The human epithelial growth factor receptor 2 (HER2) status of these tumours is largely unknown. Methods We performed a systematic electronic search of the literature and clinicopathological presentation of two cases including first-time complete assessment of HER2 status. Thirty-two patients with a mean age of 64.3 years, 87.5% of whom were male, were included in this review. Findings Half of the cases were recorded in Asia. Median follow-up was 24 months. There was no predominant site of development, while underlying histological abnormalities were present in 25%. At initial presentation, lymph node involvement was evident in 46.6% while distant metastatic disease was present in 9.3%. Presentation at stage I occurred in 55.6%. Potentially curative surgical/interventional treatment was intended in 90.6%. Recurrence occurred in 6.6%, while death was recorded in 19.2%, with cancer-related deaths reaching 11.5%. The one- and three-year survival rates were 84.2% and 79%, respectively. Our two cases displayed negative HER2 expression. Conclusions This systematic review demonstrates that this group of malignancies is very rare but possibly underdiagnosed. The disease commonly presents at early stage, mainly affecting middle-aged men. The prognosis is generally favourable even in cases of advanced disease. The HER2 expression and its correlation with the outcomes need to be further explored.

There is a lack of a national organized screening program for colorectal cancer in Greece, and asymptomatic detection is usually the result of individual decisions. The collection of epidemiologic endoscopic data from a population of interest would therefore provide valuable information for future treatment guidance, especially during periods of economic austerity. The current cross-sectional study included 380 asymptomatic, average risk individuals undergoing screening colonoscopy for the first time, during the period of one year in a tertiary public hospital in Athens. Descriptive and analytic epidemiologic data were analyzed. The prevalence of adenomas and advanced lesions were compared between the younger and older cohort, and a regression model was applied for risk evaluation. The mean age of participants was 63 years, and 53% were male. A significant proportion of patients presented with polyps (51.5%) and 25% of them had lesions in the proximal colon. The prevalence of adenomas and advanced adenomas was 29.5 and 11.8%, respectively. Similar high prevalence rates of lesions were identified in the cohort of individuals <50 years of age and the older cohort (>50 years of age). Regression models identified age, number and size of polyps as the major risk factors for the detection of adenomas. The increase of advanced lesions in the older and younger cohort requires confirmation by larger studies. Overall, the results of the present study indicate the requirement for a well-organized screening colonoscopy program starting from as early as 40 years of age. This program may confer an additional endoscopic burden with socioeconomic consequences in a country with limited health resources.

Multidrug resistance correlates with unfavourable treatment outcomes in numerous cancers including renal cell carcinoma. The expression and clinical relevance of Glutathione-S-transferase-pi (GST-pi), a multidrug resistance factor, in kidney tumors remain controversial. We analyzed the expression of GST-pi in 60 formalin-fixed, paraffin-embedded renal cell carcinoma samples by immunohistochemistry and compared them with matched normal regions of the kidney. A significantly higher expression of GST-pi was observed in 87% of clear cell carcinoma and 50% of papillary subtypes. GST-pi expression did not correlate with tumor grade or patient survival. GST-pi is unlikely to be a prognostic factor for renal cell carcinoma. However, further studies with large number of samples are warranted to establish the role of GST-pi, if any, in intrinsic or acquired resistance of renal cell carcinoma to conventional treatments.