Limiting Lynch syndrome (LS) testing to women younger than 60 years could result in missing a significant number of genetic disease, according to an article published online ahead of print in the Journal of Clinical Oncology.1

Researchers in the study sought to evaluate if tumor microsatellite instability (MSI) typing along with immunohistochemistry and MLH1 methylation analysis can help identify women with LS in endometrial cancer (EC), as the best screening practice is unknown.

A total of 1002 ECs were assessed for MSI, MLH1 methylation, and mismatch repair (MMR) protein expression. Tumors were categorized as having normal MMR, defective MMR associated with MLH1 methylation, or probable MMR mutation.

A comparison of cancer family history, demography, and clinical features was performed in each group. A subset of women was tested for Lynch mutation.

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Results showed a possible mutation in 11.8% of tumors. Lynch mutations were found in 41% of cases classified as probable mutations (21 of 51 tested). Younger age at diagnosis was linked to mutation carriers than noncarriers (54.3 vs 62.3; P < .01). Twenty-four percent of mutation carriers presented with ECs at less than 60 years.

The authors concluded that “combined MSI, methylation, and IHC analysis may prove useful in Lynch screening in EC.”

Reference

  1. Goodfellow PJ, Billingsley CC, Lankes HA, et al. Combined microsatellite instability, MLH1 methylation analysis, and immunohistochemistry for lynch syndrome screening in endometrial cancers from GOG210: an NRG Oncology and Gynecologic Oncology Group Study [published online ahead of print November 9, 2015]. J Clin Oncol. doi: 10.1200/JCO.2015.63.9518.