Comprehensive Genomic Profiling for Therapeutic Decision and Identification of Gene Mutation in Uterine Endometrial Dedifferentiated Carcinoma

Abstract

Endometrial dedifferentiated carcinoma is a new concept among endometrial malignancies, is rare, and has a poor prognosis as it is discovered in advanced stages and has no established treatment. It has higher rates of gene mutations, such as mismatch repair, than general endometrial cancer and has been associated with Lynch syndrome. However, due to its heterogeneity, case-by-case searches are needed. Comprehensive genomic profiling by Foundation One® CDx can comprehensively identify over 300 gene mutations via a next-generation sequencer and can evaluate biomarkers, such as the microsatellite status and tumor mutation burden. Therefore, it may be beneficial in identifying therapeutic targets and drugs for diseases whose treatment has not been established. In this case, 13 therapies, including immune checkpoint inhibitor therapy for microsatellite instability-High and 40 clinical trials for several gene mutations might be beneficial. We report a case of endometrial dedifferentiated carcinoma for which Foundation One® CDx gene profiling was used to propose treatment.

Dedifferentiated Endometrial Carcinoma: A Rare Aggressive Neoplasm-Clinical, Morphological and Immunohistochemical Features

“…In the Cancer Genome Atlas, EDC was reported as a heterogeneous neoplasm that had a higher number of mutations, so that it could be considered a high-risk endometrial carcinoma [30,58,[75][76][77][78]. Because of its rarity, poor prognosis, and association with an advanced stage at diagnosis as well as presence of higher rates of gene mutations than other high-risk endometrial cancers, there is no established treatment.…”

“…Because of its rarity, poor prognosis, and association with an advanced stage at diagnosis as well as presence of higher rates of gene mutations than other high-risk endometrial cancers, there is no established treatment. In addition, due to its morphological and genetic heterogeneity, to delineate a prognosis and treatment, it is important to evaluate for each case the genomic profiling [75][76][77][78]. Many authors have reported associations between the prognosis and certain gene mutations, such as mismatch repair (MMR) gene mutations, POLE, SWI/SNF complex [77][78][79][80], and Tp53 mutations [75,81].…”

“…In addition, due to its morphological and genetic heterogeneity, to delineate a prognosis and treatment, it is important to evaluate for each case the genomic profiling [75][76][77][78]. Many authors have reported associations between the prognosis and certain gene mutations, such as mismatch repair (MMR) gene mutations, POLE, SWI/SNF complex [77][78][79][80], and Tp53 mutations [75,81].…”

“…Moreover, it is important for immunohistochemical analyses to consider that this must be performed accurately without problems due to bad fixation and bad antigen preservation [74]. In addition, it is important to consider any morphological and genetic intra-tumoral heterogeneity that the neoplasm might have [30,58,[75][76][77][78]. Since Tp53 mutation represents another genetic alteration of EDC [75,76,81] agents, targeting the mutant p53 pathway could be considered for treatment of this malignancy (Table 1).…”