Mismatch repair status and outcomes after adjuvant therapy in patients with surgically staged endometrial cancer

Abstract

Objectives: To determine whether DNA mismatch repair (MMR) modifies the response to chemotherapy or radiotherapy in patients with endometrial cancer.

Methods: Immunohistochemistry (IHC) for the DNA MMR proteins MLH1, MSH2, MSH6, and PMS2 was performed on a tissue microarray of specimens of primary endometrial cancer. MMR deficiency was defined as lack of expression of one or more proteins. Expression of all proteins classified a tumor as having an intact MMR system. Recurrence rates were calculated for women treated with platinum-based chemotherapy or pelvic external beam radiation. Comparisons were made using the log-rank test. Multiple comparisons were controlled for by utilizing the Bonferroni correction method.

Results: Four hundred seventy-seven cases of endometrial cancer were evaluated on a tissue microarray (TMA). One hundred fifty-eight patients (41%) received chemotherapy. Sixty-six patients (17%) received pelvic teletherapy. Overall and progression-free survival were not different between patients whose tumors had intact MMR and those with defective MMR when stratified by adjuvant treatment with radiation or chemotherapy. Subgroup analyses stratified by histology (non-endometrioid versus endometrioid) and stage did show significant survival differences. There was a significant increase in overall (p=0.003) and progression-free (p=0.004) survival in those with MMR-deficient, non-endometrioid tumors treated with teletherapy compared to those with an intact MMR system. Improved progression-free survival was noted in patients with intact MMR with stage III/IV disease treated with adjuvant chemotherapy (p=0.031).

Conclusions: Subgroups of patients with non-endometrioid endometrial cancer and defective MMR may have improved survival after adjuvant radiotherapy. Patients with advanced stage endometrial cancer and defects in mismatch repair may receive less benefit from adjuvant chemotherapy.

Fig. 1

Overall survival for non-endometrioid patients receiving radiation therapy: Median overall survival was 5.30 vs. 2.09 years for MMR(−) and MMR(+), respectively, p=0.003.

Fig. 2

Progression-free survival for non-endometrioid patients receiving radiation therapy: Median overall survival was 5.30 vs. 2.09 years for MMR(−) and MMR(+), respectively, p=0.004.

Fig. 3

Progression-free survival for stage III/IV patients receiving chemotherapy: Median overall survival was 3.81 years for MMR(−) but was not calculable for MMR (+), p=0.031.