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Mesonephric-like adenocarcinoma of the female genital tract: possible role of KRAS-targeted treatment-detailed molecular analysis of a case series and review of the literature for targetable somatic KRAS-mutations. | LitMetric

AI Article Synopsis

  • Mesonephric-like adenocarcinomas (MLAs) are rare cancers of the female genital tract that usually have a KRAS mutation and tend to be aggressive.
  • Researchers studied eight MLAs and found that about 85% have a KRAS mutation, particularly affecting specific parts of the gene, but some have no mutation at all.
  • Only a small percentage of MLAs with a certain type of KRAS mutation can be treated with a specific drug, and the different locations of these mutations don't seem to affect how well patients do.

Article Abstract

Purpose: Mesonephric-like adenocarcinomas (MLA) of the female genital tract represent a rare and relatively recently described neoplasm exhibiting characteristic morphologic and immunohistochemical findings commonly associated with a KRAS-mutation. Most cases display an aggressive clinical behavior, but knowledge about treatment approaches is limited, especially for targeting KRAS.

Methods: We report a series of eight cases with a detailed molecular analysis for KRAS. These cases as well as the data of previously published cases with detailed information regarding KRAS-mutational events were reviewed for a potential targeted approach and its prognostic impact.

Results: Both the uterine and ovarian MLA harbor a somatic KRAS-mutation in about 85% of the reported cases, affecting the hotspot codons 12 and 13. 15.7% of the endometrial and 15.6% of ovarian MLA are wild type for KRAS. A p.G12A-alteration was seen in 5.6% (5/89) of the endometrial and in 6.2% (2/32) of the ovarian tumors, for p.G12C in 7.9% and 6.2%, for p.G12D in 32.6% and 34.5% and for p.G12V in 36% and 37.5%, respectively. Very limited data are available regarding the prognostic impact of different mutational sites within the KRAS-gene without significant prognostic impact.

Conclusion: Because of a specific p.G12C-KRAS somatic mutation, only the minority of MLA (7.9% with uterine and 6.2% with ovarian primary) are potentially targetable by sotarasib in that rare but aggressive subtype of adenocarcinoma of the female genital tract. Until now, the different location of a somatic KRAS-mutation is of no prognostic impact.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620254PMC
http://dx.doi.org/10.1007/s00432-023-05306-9DOI Listing

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