Evaluation of Clinical Criteria for the Identification of Lynch Syndrome among Unselected Endometrial Cancer Patients.

Bruegl AS1, Djordjevic B, Batte B, Daniels MS, Fellman BM, Urbauer DL, Luthra R, Sun C, Lu K, Broaddus RR.

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Abstract

Clinical criteria, primarily young age of cancer onset and family history of signature cancers, have been developed to identify individuals at elevated risk for Lynch Syndrome with the goals of early identification and cancer prevention. In 2007, the Society of Gynecologic Oncology (SGO) codified criteria for women presenting with gynecologic cancers. These criteria have not been validated in a population-based setting. For 412 unselected endometrial cancers, immunohistochemical expression of DNA mismatch repair proteins and MLH1 methylation were assessed to classify tumors as sporadic or probable Lynch Syndrome. In this cohort, 10.5% of patients were designated as probable Lynch Syndrome based on tumor testing. The sensitivity and specificity of SGO criteria to identify these same cases were 32.6% (95% CI 19.2-48.5) and 77% (95% CI 72.7-81.8), respectively. With the exception of tumor location in the lower uterine segment, multivariate analysis of clinical features, family history, and pathologic variables failed to identify significant differences between the sporadic and probable Lynch Syndrome groups. A simplified cost-effectiveness analysis demonstrated that SGO clinical criteria and universal tissue testing strategies had comparable costs per probable Lynch Syndrome patient identified. In conclusion, SGO criteria successfully identify probable Lynch Syndrome cases among women with endometrial cancer who are young or have significant family history of signature tumors. However, a larger proportion of probable Lynch Syndrome patients who are older and have less significant family history are not detected by this screening strategy. Universal tissue testing may be necessary to capture more individuals at risk for having Lynch Syndrome.