[1112] Screening by Young Age and Family History of Colon Cancer Misses the Majority of Endometrial Cancer Patients with Lynch Syndrome

A Bruegl, B Djordjevic, B Fellman, D Urbauer, R Luthra, R Broaddus. MD Anderson Cancer Center, Houston, TX; University of Ottawa, Ottawa, ON, Canada

Background: Current clinical screening guidelines to identify women with Lynch Syndrome rely heavily on young age at diagnosis of endometrial cancer (EC) or colorectal cancer and presence of family history of colon cancer. Such guidelines were codified by the Society of Gynecologic Oncologists (SGO) in 2007. These guidelines have not been tested in a population-based fashion.
Design: 408 consecutive, unselected EC cases were evaluated for immunohistochemical expression of DNA mismatch repair proteins. Tumors with loss of MSH2, MSH6 or PMS2 were designated as probable Lynch Syndrome (PLS). Tumors with loss of MLH1 and absence of MLH1 promoter methylation were also designated PLS. Clinical data were collected from the electronic medical record.
Results: 43/408 (10.5%) EC tested had PLS. 29/43 (67.4%) EC cases with PLS did not meet SGO criteria. Table 1 summarizes known Lynch Syndrome risk factors for the 43 PLS patients. Those who met SGO Criteria were younger, more frequently had tumor rising in lower uterine segment, and more frequently had a family history of colon cancer. Note that the majority of EC cases with PLS in both groups did not have these historical risk factors.

Clinical Data for n=43 Endometrial Cancer Patients with Probable Lynch Syndrome
 Meets SGO Criteria (n=14)Does Not Meet SGO Criteria (n=29)
Median age at Diagnosis48.563.0
Average BMI32.033.0
BMI less than 307/14 (50.0%)10/29 (34.5%)
Family History Endometrial Cancer2/14 (14.3%)2/29 (6.9%)
Family History Colorectal Cancer4/14 (28.6%)4/29 (13.8%)
Lower Uterine Segment Tumor3/14 (21.4%)2/29 (6.9%)

Conclusions: When population-based screening is employed, 10.5% of EC patients have tissue testing findings consistent with Lynch Syndrome. This percentage is comparable to those in recent publications from the Netherlands and Ohio State. SGO Criteria correctly identified only 32.6% of these women, meaning that a large number of endometrial cancer patients miss the opportunity for further cancer risk assessment and heightened screening for colorectal cancer. As germline mutation testing of all endometrial cancer patients is not economically feasible, to capture the majority of women who have Lynch Syndrome, universal tumor testing (immunohistochemistry, MLH1 methylation) of endometrial cancers should be employed.
Category: Gynecologic & Obstetrics

Monday, March 4, 2013 8:00 AM

Proffered Papers: Section E, Monday Morning


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