Ki Heon Lee

Clinicopathologic significance of mismatch repair protein expression in endometrioid endometrial cancer

To evaluate the association between mismatch repair (MMR) protein expression and clinico-pathologic outcomes in patients with endometrioid endometrial cancer (EC). A retrospective review of the clinico-pathologic outcomes was performed on patients who were diagnosed with EC and had results of MMR protein immunohistochemistry. MMR-deficient (MMR-d) was defined as absence of expression in any of the 4 MMR proteins (MLH1, MSH2, MSH6, and PMS2). Demographics, pathologic variables, and survival outcomes were compared according to the MMR status. A total of 193 EC patients with available MMR expression data were included, of whom 163 patients had endometrioid type EC. Overall, 44 patients (27.0%) were classified as MMR-d. Compared with MMR-proficient (MMR-p) group, MMR-d group was associated with more frequent lymphovascular space invasion (LVSI, p = 0.001). MMR-d was also related with higher risk of lymph node (LN) metastasis in endometrioid type EC (p = 0.008), especially para-aortic LN metastasis. During the median follow-up period of 19.1 months (1-44.5), MMR-d group, especially MLH1/PMS2 subgroup, showed a tendency of reduced PFS (p = 0.036 and p = 0.008, respectively). On Cox regression analysis, however, LN metastasis remained as the only independent risk factor for PFS (p = 0.004) in endometrioid EC, and MLH1/PMS2 loss showed a marginally significant association (p = 0.054). Our findings of the associations between MMR deficiency and poor prognostic factors, such as LVSI and LN metastasis, may suggest the prognostic value of MMR status in EC and need further prospective validation studies.

Role of systematic lymphadenectomy in patients with intermediate to high-risk early stage endometrial cancer

To determine the clinical significance of systematic lymph node dissection (LND) and to better define the relevant extent of LND in intermediate- to high-risk early stage endometrial cancer (EC). Patients who received surgery as a primary treatment of histologically confirmed EC and preoperatively considered as uterus-confined early stage disease were included in the study population. The rates of lymph node metastasis (LNM) according to the risk groups and anatomic sites were assessed. Univariate and multivariate analyses were performed to evaluate risk factors for recurrence. A total of 804 patients were included in the study analysis. The rates of LNM were significantly different according to the risk group; 1.2% in low-risk, 20.1% in intermediate-risk, and 30.0% in high-risk group. When assessing the rates of LNM in individual anatomic sites, positive LNs were evenly distributed throughout the pelvic and para-aortic regions. In the intermediate to high-risk EC cases, the rates of para-aortic LNM below and above inferior mesenteric artery (IMA) were 11.1% and 12.5%, respectively. On multivariate analysis, LNM was the only independent risk factor for recurrence in the intermediate to high-risk EC (hazard ratio=2.63, 95% confidence interval=1.01-6.82, p=0.047). LNM was frequently observed in intermediate- and high-risk early stage EC and it served as an independent risk factor for recurrence. When considering the similar rates of LNM between below and above IMA, nodal assessment needs to be performed up to the infra-renal level, especially for the staging purpose in high-risk EC.