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The detection of isochromosome i[12p] in malignant germ cell tumours and tumours with somatic malignant transformation using qPCR.
Histopathology 2020 September 25
Malignant germ cell tumours (GCT) of the testis are rare neoplasms, but the most common solid malignancy of young men. WHO guidelines divide GCT into five types for which numerous immunohistochemical markers allow the exact histological subtyping in the majority of the cases. In contrast, the germ cell origin is often hard to prove in metastatic GCT that have developed so-called somatic malignant transformation. A high percentage of up to 89% of germ cell tumours are characterized by the appearance of an isochromosome 12p (i[12p]). Fluorescence-in-situ-hybridization has been the most common diagnostic method for the detection of i[12p] so far with the disadvantages of being time consuming, demanding and not being a stand-alone method. In the present study, we established a quantitative PCR assay as an independent method to detect i[12p] and regional amplifications of the short arm of chromosome 12 using DNA extracted from formalin-fixed and paraffin-embedded tissue. A cut off value to distinguish between presence and absence of i[12p] was established in a control set consisting of 36 tumour-free samples. In a training set of 149 GCT samples, i[12p] was detectable in 133 tumours (89%) whereas 16 tumours (11%) showed no i[12p]. In a test set containing 27 primary and metastatic GCT, all 16 tumours with metastatic spread and/or somatic malignant transformation were successfully identified by the detection of i[12p]. In summary, the here presented quantitative PCR assay can help to identify, further characterize and assign a large part of histologically inconclusive malignancies to a GCT origin.
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