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Publication
Next-generation sequencing in endometrial cancer diagnosis: benefits and pitfalls
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Abstract(s)
Endometrial cancer (EC) is a heterogeneous gynecological pathology whose classification has evolved significantly, incorporating classical histological charcaterization with a new molecular approach based on data from the TCGA study (The Cancer Genome Atlas Program). The new classification uses a diagnostic algorithim that includes the immunohistochemical study (IHC) of p53 and NMR proteins, along with the detection of mutations in the POLE gene. The aim of this study was to evaluate the benefits and disadvantages of NGS in the diagnosis of EC in a retrospective series of 233 patients with EC. This assessment was conducted by analyzing previously obtained NGS data related to mutations in the exonuclease domain of the POLE gene, as well as the correlation of NGS and IHC data to evaluate changes in the TP53 and MMR genes. NGS data related to germline variants associated with hereditary syndromes were also analyzed. A total of 217 cases showed concordance between NGS and IHC techniques, and additionally in six cases it was possible to identify germline variants in genes associated with hereditary predisposition syndromes. The 233 cases were molecularly classified into: 11% POLE mutated (POLEmut), 24% MMR deficient (dMMR), 31% p53 abnormal (p53abn) and 34% with no specific molecular profile (NSMP). The study demonstrates that NGS, despite being an expensive and time-consuming technique, offers a comprehensive assessment in the diagnosis of EC: it allows the identification of mutations in POLE and other relevant genes, such as TP53 and MMR, directly impacts the prognosis and therapeutic management of patients and, in addition, it is useful to diagnose hereditary syndromes in the patients under study.
Description
Keywords
Endometrial cancer Molecular diagnostic algorithm Next generation sequencing Immunohistochemistry