5579 Background: The significance of the hereditary basis of endometrial cancer is apparent in young women with endometrial cancer. The objective of this study was to describe the incidence and prognostic implications of DNA mismatch repair protein defects in a series of patients age 40 years and younger with endometrial cancer. Methods: We performed a retrospective cohort study of patients age 40 years or less who were diagnosed with endometrial carcinoma between 1/93 and 5/08. Clinical and pathologic data were extracted from medical records. Paraffin-embedded slides from hysterectomy specimens were obtained and DNA mismatch repair (MMR) immunohistochemistry (IHC) was performed. Cases were analyzed according to presence of DNA MMR protein defects. Standard two-sided statistical tests were performed. Results: Of the 71 identified patients, the median age was 37 years (range, 24–40), with a median follow-up of 47 months (range, 1–178). The majority were of endometrioid histology (94%), stage I (73%), and FIGO grade 1 (61%). IHC was performed with available blocks (n = 56), and loss of DNA MMR was found in 9 cases (16%). Cases with loss of DNA MMR were more likely to have high-grade (FIGO 2 or 3) tumors (p < 0.001), be advanced stage (III or IV) at the time of diagnosis (p < 0.001), and have a family history suggestive of hereditary non-polyposis colorectal cancer (p = 0.01). There was no difference between the groups in histology, obesity (BMI>30), parity, or history of infertility. Analysis of clinical outcomes revealed that cases with loss of DNA MMR had significantly worse overall survival (median survival not reached, log rank p = 0.018). At the time of last follow-up, 2 (22%) patients with loss of DNA MMR were dead of disease compared with 2 (4%) patients with retained DNA MMR. Conclusions: Endometrial cancer is rare in young women age 40 years or less. In these patients, loss of DNA MMR was associated with worse clinicopathologic factors (high-grade and advanced-stage tumors) and worse outcome. Other clinical risk factors associated with endometrial cancer were not associated with loss of DNA MMR. The data suggest that MMR testing in women 40 years of age or younger with endometrial cancer may have clinically useful prognostic information. No significant financial relationships to disclose.
Nicotinamide N-methyltransferase expression and its association with phospho-Akt, p53 expression, and survival in high-grade endometrial cancer