The Importance of FISH signal cut-off values for 9p21 deletion in malignant pleural mesothelioma: Is it underestimated?

Publication date: Available online 4 March 2019Source: Pathology - Research and PracticeAuthor(s): Gamze Kulduk, Özgür Ekinci, Gizem Toker, Umut Demirci, Esra Özaydın, Nalan Akyürek, Leyla MemişAbstractMalignant mesothelioma (MM) is an aggressive cancer with a poor prognosis. The most common genetic alteration in MM is the deletion of the INK4a/ARF locus, which encodes the p16 protein and is located on the short arm of chromosome 9 (9p21). Recently, it has been shown that homozygous deletion of 9p21 has both diagnostic and prognostic significance in MM. It is a known fact that, to interpret fluorescence in situ hybridization (FISH) signals, a cut-off value for each probe should be determined for a correct diagnosis. To our knowledge, there is no consensus or confirmed protocol for cut-off values to evaluate FISH signals in MMs. Therefore, the aim of our research was to address 9p21 deletion status and p16 expression profiles of MM by determining our own cut-off values and the effectiveness of using p16 negativity and 9p21 deletion as markers for differentiating MMs from benign mesothelial proliferations in 114 cases. We established a cut-off value for the detection of 9p21 deletion by using 13 benign reactive cases (6 reactive mesothelial hyperplasias and 7 chronic fibrinous pleuritis cases) and found between 0-7%. According to our calculations, homozygous deletion was defined by loss of both p16 gene signals in at least 13.3% of the nuclei that showed at least 1 signal...
Source: Pathology Research and Practice - Category: Pathology Source Type: research