Genome-wide linkage screen for testicular germ cell tumour susceptibility loci

A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the diseas

Natural history of renal cell carcinoma: An immunohistochemical analysis of growth rate in patients with delayed treatment

To investigate the natural history of renal cell carcinoma (RCC) with delayed treatment and to immunohistochemically analyze the correlation between some biomarkers and the growth rate of RCC. Methods: We reviewed our institutional databases to identify renal tumors which were confirmed to be RCC by delayed surgical treatment after at least 12 months of active surveillance (AS). Growth rate was defined as the average growth rate of the maximal diameter on computed tomography or magnetic resonance imaging. The clinicopathological characteristics and immunohistochemical biomarkers (Ki-67, p53, bcl-2, and vascular endothelial growth factor) were analyzed the correlation with the growth rate of RCC. Results: We identified 45 RCCs from 45 patients. The mean patient age was 54 years (range, 26–78 years). The mean tumor size increased from 2.39 cm (range, 0.10–6.70 cm) at presentation to 4.54 cm (range, 1.40–11.80 cm) after a mean time of 45.4 months (range, 12–155 months) of AS. The mean growth rate was 0.79 cm/y (range, 0.10–4.74 cm), and 36 (80.0%) tumors presented a growth rate ≤ 1.00 cm/y. Clear cell RCC had a trend of growing faster than other histological subtypes. Pathological grade was significantly correlated with the growth rate of RCC (p = 0.043). High positive ratio of Ki-67 (r = 0.351, p = 0.018) and being p53 positive (p = 0.019) were significantly correlated to the fast growth rate of RCC. Conclusion: In general, RCCs under AS are slow growing with a wide variation of growth rate, with a portion of RCCs presenting rapid growth kinetics. RCC with rapid growth during AS is characterized by a high histological grade, high positive ratio of Ki-67, and being p53 positive