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Aim: To analyze genetic alterations of p53 gene in Slovenian gastric cancer patients and to compare these alterations with clinicopathological parameters in order to assess the value of p53 as a prognostic factor., Methods: We analyzed the samples from 230 Slovenian patients with gastric cancer, collected between 1983 and 2001. p53 expression was evaluated immunohistochemically with DO-7 monoclonal antibody. In addition, loss of heterozigosity (LOH) and microsatellite instability (MSI) of p53 gene were evaluated, as well as its mutational status in the selected population of patients., Results: p53 expression was associated with poorer survival and it was an independent predictor in multivariate analysis, along with TNM (T--size of tumor, N--nodal involvement, M--distant metastasis) stage status. Loss of heterozigosity and microsatellite instability status did not influence survival, however we found association of loss of heterozigosity with Lauren's (Mantel-Haenszel test, P=0.004) and Ming's (Mantel-Haenszel test, P<0.001) classification, whereas microsatellite instability was associated with gender (Mantel-Haenszel test, P=0.017), TNM stage (chi(2) test, P=0.006) of gastric cancer, and lymph node involvement (pN) (chi(2) test, P=0.004). Conclusions. The data on p53 abnormalities, when considered separately, could be of relative value for predicting the behavior of gastric tumors. However, our analyses showed that studying p53 overexpression, loss of heterozigosity, microsatellite instability, and mutational analysis could provide data that, particularly in combination with some clinicopathological features, might be of clinical value for predicting the tumor behavior and patient response to therapy.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder caused by mutations in at least two different loci. Prior to performing mutation screening, if DNA samples of sufficient number of family members are available, it is worthwhile to assign the gene involved in disease progression by the genetic linkage analysis., Methods: We collected samples from 36 Slovene ADPKD families and performed linkage analysis in 16 of them. Linkage was assessed by the use of microsatellite polymorphic markers, four in the case of PKD1 (KG8, AC2.5, CW3 and CW2) and five for PKD2 (D4S1534, D4S2929, D4S1542, D4S1563 and D4S423). Partial PKD1 mutation screening was undertaken by analysing exons 23 and 31-46 and PKD2 ., Results: Lod scores indicated linkage to PKD1 in six families and to PKD2 in two families. One family was linked to none and in seven families linkage to both genes was possible. Partial PKD1 mutation screening was performed in 33 patients (including 20 patients from the families where linkage analysis could not be performed). We analysed PKD2 in 2 patients where lod scores indicated linkage to PKD2 and in 7 families where linkage to both genes was possible. We detected six mutations and eight polymorphisms in PKD1 and one mutation and three polymorphisms in PKD2., Conclusion: In our study group of ADPKD patients we detected seven mutations: three frameshift, one missense, two nonsense and one putative splicing mutation. Three have been described previously and 4 are novel. Three newly described framesfift mutations in PKD1 seem to be associated with more severe clinical course of ADPKD. Previously described nonsense mutation in PKD2 seems to be associated with cysts in liver and milder clinical course.

Synovial sarcoma (SS) is characterized by the t(X;18)(p11.2;q11.2) chromosomal translocation, which results in generating either SYT-SSX1, SYT-SSX2 or, infrequently, SYT-SSX4 fusion gene. The ratio of SYT-SSX1:SYT-SSX2 fusions is close to 2:1 in the majority of studies, and SYT-SSX2 fusion has been only rarely observed in biphasic SS. In the present study, we compared two series of patients with SS, Slovenian (37 cases) and Dutch (14 cases), with respect to clinical, pathological and molecular findings. The two groups did not differ with regard to clinicopathological features. Whereas the frequency of different SYT-SSX fusions in the Dutch group was similar to that reported in the literature, we found an unexpectedly high number of tumors with SYT-SSX2 fusion in the Slovenian group. The ratio of SYT-SSX1:SYT-SSX2 fusion was 7:18 for monophasic and 2:7 for biphasic tumors in the Slovenian group. This distribution differs significantly from that observed in the Dutch group in the present study (P = 0.041) as well as from data reported in the recent large multi-institutional study on 243 patients (P = 0.0001). Our findings indicate possible geographical differences in the frequency of two SYT-SSX fusion transcripts in patients with synovial sarcoma.