Many facets of chromosome 3p cytogenetic findings in clear cell renal carcinoma: the need for agreement in assessment FISH analysis to avoid diagnostic errors.

Abnormalities of the locus chromosome 3p and the entire chromosome 3 are involved in the cancerogenesis of clear cell renal carcinoma and may be detected by interphase fluorescence in situ hybridization (interphase FISH). We observed a variable detection rate of chromosome 3p/3 abnormalities in different series of clear cell renal carcinoma. Therefore, we focused on problematic issues when performing analysis on routinely available formalin-fixed and paraffin embedded tissue. A group of studies encountered a single approach to chromosome 3p detection, by using probe/s to map different codes of the short arm 3p without a control of the entire chromosome 3. Deletion of chromosome 3p and monosomy of chromosome 3 ranged from 38% to 100% in clear cell renal carcinoma. Cut-off values for the threshold were chosen randomly or obtained by calculation of the mean value plus 1 or 2 or 3 standard deviations. Loss of chromosome 3p was assessed either as the percentage of single signals on the total number of nuclei, or applying a double approach with corrections of control chromosome 3. Moreover, cut off values were sometimes arbitrarily corrected with the findings from normal adjacent renal parenchyma. A consensus of experts in the field is needed in order to define the best methodological approach and the appropriate threshold in assessment 3p deletion when interphase FISH is performed in clear cell renal carcinoma. This harbours relevant diagnostic and therapeutic implications, at light also of targeted therapies recently available to clear cell renal carcinoma.

Utility of tissue microarrays for assessment of chromosomal abnormalities in chromophobe renal cell carcinoma.

OBJECTIVE: To compare the results of numerical chromosomal changes in chromophobe renal cell carcinoma obtained from whole tissue sections with those of tissue microarrays. STUDY DESIGN: Standard sections and tissue microarrays constructed from formalin-fixed and paraffin-embedded chromophobe renal cell carcinomas from 6 patients were subjected to interphase fluorescence in situ hybridization (FISH) using centromeric probes for chromosome 1, 2, 6, 10 and 17. Tissue microarrays were constructed with 3 cores per tumor and 2 cores of normal renal tissue controls. RESULTS: Whole sections of chromophobe renal cell carcinoma showed multiple chromosomal abnormalities in 3 out of 6 cases (case 1, 2, 5). In 2 cases all 5 chromosomes were lost in both whole and tissue microarray cores (cases 2 and 5), and for 1 case (case 1) losses of chromosomes 2, 10 and 17 were detected on both whole and tissue microarray cores. In another 2 cases there were 2 fluorescence signals for chromosomes 1 in the majority of malignant cells (cases 3 and 6), loss of chromosome 6 (case 3), loss of chromosome 2 (case 6) and a mosaic pattern with nuclei showing a mixture of signal losses and gains for the other chromosomes. The remaining tumor did not show abnormalities (case 4). When 2 core biopsies per tumor were examined, the level of substantial concordance of results ranged from 92% to 98%. CONCLUSION: In this study we have demonstrated that tissue microarrays are a valid substitute for whole tissue sections in large cohort studies of chromophobe renal cell carcinoma when FISH analysis is undertaken. Concordance of results was improved when the number of analyzed cores was increased from 2 to 3, at which point a concordance index ranging from substantial to almost perfect was observed.