https://www.europeanurology.com/article/S0302-2838(10)00699-8/pdf/prognostic-and-therapeutic-impact-of-the-histopathologic-definition-of-parenchymal-epithelial-renal-tumors

Prognostic and Therapeutic Impact of the Histopathologic Definition of Parenchymal Epithelial Renal Tumors

Adult Renal Cell Carcinoma: A Review of Established Entities from Morphology to Molecular Genetics

We investigated the usefulness of interphase fluorescence in situ hybridization (FISH) analysis to differentiate between 11 chromophobe renal carcinomas and 12 renal oncocytomas, showing different clinical outcomes, when compared with conventional metaphase cytogenetics by karyotyping. Karyotypically, 3 chromophobe renal cell carcinomas showed losses of chromosomes, 3 were polyploid, 1 was normal, and 4 failed to grow. Of 12 oncocytomas, 5 showed a normal numeric karyotype and 6 additional structural rearrangements. FISH on chromophobe renal cell carcinomas showed a high percentage of cases (10/11 [91%]) with multiple numeric losses among chromosomes 1, 2, 6, 10, and 17; this interphase pattern was observed irrespective of the 3 different metaphase karyotypes. Of 12 oncocytomas, 11 (92%) revealed a normal numeric chromosomal status showing at least 2 chromosomes without aneusomy by interphase FISH. The study demonstrates that indeed FISH performed on formalin-fixed, paraffin-embedded tissue can provide clinically useful information more reliably than karyotyping of most of these tumors.

/pdf/diagnostic-usefulness-of-fluorescent-cytogenetics-in-wsrj59ialv.pdf

Diagnostic Usefulness of Fluorescent Cytogenetics in Differentiating Chromophobe Renal Cell Carcinoma From Renal Oncocytoma: A Validation Study Combining Metaphase and Interphase Analyses

Squamous lung carcinoma lacks specific “ad hoc” therapies. Amplification of chromosome 3q is the most common genomic aberration and this region harbours genes having role as novel targets for therapeutics. There is no standard definition on how to score and report 3q amplification. False versus true 3q chromosomal amplification in squamous cell lung carcinoma may have tremendous impact on trials involving drugs which target DNA zones mapping on 3q. Forty squamous lung carcinomas were analyzed by FISH to assess chromosome 3q amplification. aCGH was performed as gold-standard to avoid false positive amplifications. Three clustered patterns of fluorescent signals were observed. Eight cases out of 40 (20%) showed ≥8 3q signals. Twenty out of 40 (50%) showed from 3 to 7 signals. The remaining showed two fluorescent signals (30%). When corrected by whole chromosome 3 signals, only cases with ≥8 signals maintained a LSI 3q/CEP3 ratio >2. Only the cases showing 3q amplification by aCGH (+3q25.3−3q27.3) showed ≥8 fluorescent signals at FISH evidencing a 3q/3 ratio >2. The remaining cases showed flat genomic portrait at aCGH on chromosome 3. We concluded that: 1) absolute copy number of 3q chromosomal region may harbour false positive interpretation of 3q amplification in squamous cell carcinoma; 2) a case results truly “amplified for chromosome 3q” when showing ≥8 fluorescent 3q signals; 3) trials involving drugs targeting loci on chromosome 3q in squamous lung carcinoma therapy have to consider false versus true 3q chromosomal amplification.

https://helda.helsinki.fi/bitstream/handle/10138/42134/True_3q_chromosomal_amplification_in_squamous_cell_lung_carcinoma_by_FISH_and_aCGH_molecular_analysis_impact_on_targeted_drugs..pdf?sequence=2

True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.

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.

https://digitum.um.es/digitum/bitstream/10201/49412/1/Brunelli-26-1207-1213-2011.pdf

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

Renal cell neoplasms are a heterogeneous group of tumours in terms of pathological features and prognostic behaviour. The genetics of these tumours may aid in correct diagnosis and accurate assessment of prognosis. In ambiguous cases it may be necessary to utilise new markers that are capable of further discerning renal cell neoplasms. Fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue is an increasingly useful technique in the detection of many diagnostic chromosomal abnormalities, among which chromosomes 1, 2, 3p, 6, 7, 10, 17 and Y are the most common. The addition of FISH to histological evaluation improves the diagnostic accuracy of core biopsies from renal masses, which may have an important impact in clinical management of many cases due to newer therapeutic approaches, including cryo- or radiofrequency ablation, nephron-sparing surgeries and target therapies.

Fluorescent cytogenetics of renal cell neoplasms.

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Fluorescent cytogenetics of renal cell neoplasms.