Introduction/Background Primary endometrial neuroendocrine carcinoma (PENEC) is a histological type with a very poor prognosis compare to the other histological type in endometrial cancer. However because of the rarity, an effective adjuvant chemotherapy regimen has not been established. In recent years, it has been reported that the mutation frequency of mismatch repair (MMR) genes is as high as 44% in 8 of 18 cases. Since PENEC is extremely rare, there is no accumulation of cases or additional reports, and there is also no study in Japan.

Methodology In this study, we investigated the frequency of MMR gene mutations and its treatment outcomes in 15 cases of PENEC diagnosed between 2011 and 2021 at 7 institutions approved by the Juntendo University Institutional Review Board.

Results The histological types of 15 cases were pure large cell NEC (LCNEC) 2 cases, pure small cell NEC (SCNEC) 4 cases, endometrioid carcinoma+ LCNEC 3 cases, endometrioid carcinoma + SCNEC 4 cases and carcinosarcoma + SCNEC 2 cases. Of the 15 cases, 46.7% of the 7 cases presented with MMR gene mutations. The patterns of MMR gene mutations were MLH-1+PMS-2 mutation in 6 cases and MSH-2 mutation in 1 case. The PFS was 8.5 months and 10 of 15 cases had recurrence within 3 years. Of the 7 patients with MMR gene mutations, 2 patients who received pembrolizumab both showed partial response. This study suggests that MMR gene mutations are also recognized at a high rate of 46.7% in PENEC in Japan.

Conclusion In the case of PENEC, we should investigate the microsatellite instability (MSI) at the time of recurrence, and if itshowed MSI-high, pembrolizumab administration should be considered. In addition, it will be necessary to plan clinical trials to examine the additional effect of pembrolizumab at the first adjuvant chemotherapy.