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[Analysis of microsatellite instability in endometrial cancer: The significance of minimal microsatellite shift]
1Department of Pathology, Peking University First Hospital, Beijing 100034, China.
Objective:
To analyze the differences and characteristics of microsatellite instability (MSI) in endometrial cancer (EMC), by using colorectal cancer (CRC) as control.
Methods:
In the study, 228 cases of EMC were collected. For comparative analysis, 770 cases of CRC were collected. Mismatch repair (MMR) expression was detected by immunohistochemistry (IHC), and microsatellite instability (MSI) was analyzed by PCR and capillary electrophoresis fragment analysis (MSI-PCR). MSI-PCR was detected using five mononucleotide repeat markers: BAT-25, BAT-26, NR-21, NR-24, and MONO-27.
Results:
In EMC, we found 27.19% (62/228) of deficient mismatch repair (dMMR) using IHC, significantly higher than CRC (7.79%, 60/770). Meanwhile, subclonal expression of MMR protein was found in 4 cases of dMMR-EMC and 2 cases of dMMR-CRC. According to the criteria of major micro-satellite shift, we found 16.23% (37/228) of MSI-high (MSI-H), 2.63% (6/228) of MSI-low (MSI-L), and 81.14% (185/228) of microsatellite stability (MSS) in EMC using MSI-PCR. The discor-dance rate between MMR-IHC and MSI-PCR in EMC was 11.84% (27/228). In CRC, we found 8.05% (62/770) of MSI-H, 0.13% (1/770) of MSI-L, and 91.82% (707/770) of MSS. The discordance rate between MMR-IHC and MSI-PCR in CRC was only 0.52% (4/770). However, according to the criteria of minimal microsatellite shift, 12 cases of EMC showed minimal microsatellite shift including 8 cases of dMMR/MSS and 4 cases of dMMR/MSI-L and these cases were ultimately evaluated as dMMR/MSI-H. Then, 21.49% (49/228) of EMC showed MSI-H and the discordance rate MMR-IHC and MSI-PCR in EMC decreased to 6.58% (15/228). No minimal microsatellite shift was found in CRC. Compared with EMC group with major microsatellite shift, cases with minimal microsatellite shift showed younger age, better tumor differentiation, and earlier International Federation of Gynecology and Obstetrics (FIGO) stage. There were significant differences in histological variant and FIGO stage between the two groups (P < 0.001, P=0.006).
Conclusion:
EMC was more prone to minimal microsatellite shift, which should not be ignored in the interpretation of MSI-PCR results. The combined detection of MMR-IHC and MSI-PCR is the most sensitive and specific method to capture MSI tumors.
