Application of immunocytochemical and molecular analysis of six genes in liquid‐based endometrial cytology

Background

The Yokohama System of Endometrial Cytology has been used for reporting endometrial cytology, which includes gray zone category, atypical endometrial cells (ATEC), subdivided into ATEC-US and ATEC-AE. ATEC-US has been reported to be correlated with malignancy in nearly 10% of the cases. For accurate diagnosis, application of ancillary techniques on endometrial cytology was investigated.

Methods

Thirty-seven liquid based cytological specimens (SurePath™) with diagnosis of ATEC or malignant which have corresponding histological specimens, were subjected to immunocytochemical analysis for β-catenin, ARID1A, and PTEN. Hot spots of mutations for KRAS, BRAF and PIK3CA were evaluated by using i-densy system (ARKRAY).

Results

In endometrial samples with the diagnosis of ATEC and malignant, aberrant gene expressions and/or gene mutations for β-catenin, ARID1A, PTEN, KRAS, BRAF, and PIK3CA were observed in 32.4, 18.9, 37.8, 18.8, 0, and 37.1%, respectively. When any of the genes had aberrant expression or mutation, only sensitivity was better than that of cytology (77 vs. 53.8%). However, specificity, positive predictive value, negative predictive value, and accuracy was better in cytology than those of ancillary techniques. Increasing rate of abnormality according to the consequent histology results was observed in ARID1A (p = .015). Frequent loss of PTEN immunostaining (45.8%) and PIK3CA mutation (43.5%) was observed in the cases with consequent benign histology results.

Conclusion

In ATEC category of endometrial cytology, gene expression and mutation analysis of six genes were insufficient to aid conventional cytological diagnoses albeit increased sensitivity. Further investigation would be necessary.

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