Allelic losses and genomic instability in renal neoplasms

Objectives - Tumorigenesis of renal neoplasm, notably renal cell carcinoma (RCC) involves accumulation of several genetic alterations. Our aim was to establish the rate of loss of heterozygosity (LOH) on the short arm of chromosome 3 (3p) in a panel of 92 sporadically occurring renal tumors, correlate the pattern of genetic alteration(s) with disease phenotype, look for regions displaying allelic loss and genomic instability (GI) patterns in these tumors. Materials and Methods - Ninety two paired, tumor and normal paraffin-embedded tissues of patients with histopathological diagnosis of RCC or other renal neoplasms were retrieved. DNA was extracted, radioactive incorporation of labeled ATP into polymerase chain reaction (PCR) amplification was carried out and seperated on acrylamide gels followed by autoradiography Results - The RCC patients were subdivided into three groups according to tumor size. The table shows number of patients in each group, tumor size, rate of LOH and rate of capsular invasion. A B C No of patients 18 31 38 Tumor diameter <3cm 3-5.5cm >5.5cm Patients with LOH 55% 58% 63% LOH of 2 or more markers 1/10(10%) 5/18(28%) 11/24(46%) Capsular invasion 0 7% 32% Overall, 52 RCC (52/87 = 60%) displayed LOH with at least one polymorphic marker from chromosome 3p. The differences in rate of LOH were not statistically significant between the three groups. There was a direct correlation between tumor size, capsular invasion and loss of more than one marker. In group A one tumor had LOH with more than 1 marker (10%), whereas in groups B and C this subset included 5/18 (28%) and 11/24 (46%), respectively. LOH was found in two out of three patients with multifocal RCC 1 of 5 patients with papillary RCC and 1 of 3 oncocytomas displayed allelic loss. Overall GI was found in five patients. Of two renal pelvis transitional cell carcinoma one displayed GI. Conclusions - LOH at more than one locus correlates with increased tumor size and microinvasion. DNA mismatch repair genes are probably involved in pathogenesis of renal neoplasia.