[649] Microstatellite Instability and DNA Mismatch Repair Protein Deficiency in Chinese Patients with Sporadic Colorectal Cancer

Dan Huang, Xiaochen Chen, Baohua Yu, Weiqi Sheng, Xiang Du. Fudan University Cancer Center, Shanghai, China

Background: Sporadic colorectal carcinoma (SCRC) is one of the most common malignancies in the world, and its incidence is highly increased with the changes of lifestyle in Chinese. Researches suggest some SCRCs are developing through the replication error pathways, which could be detected by microsatellite instability (MSI) or DNA mismatch repair (MMR) proteins. This study was to evaluate the prevalence of MSI and loss of MMR protein expression in Chinese.
Design: An auto-immunohistochemical staining including 4 antibodies(MLH1, MSH2, PMS2 and MSH6) were used in the paraffin embedded tissue samples from 452 SCRCs. A total of 144 SCRCs including all MMR protein abnormalities performed MSI testing using PCR amplification for five microsatellite locus (BAT25, BAT26, D2S123, D5S346 and D17S250).
Results: MMR protein deficiency was seen in 43 of 452 (9.51%) SCRCs. The loss of expression of MLH1, MSH2, PMS2 and MSH6 was identified in 29/452(6.42%), 5/452(1.11%), 29/452(6.42%) and 11/452(2.43%), respectively. The most common concurrent loss was MLH1 and (observed in 25/452), followed by MSH2 and MSH6 (4/452).

The abnormality of four MMR proteins was detected in one case. For 144 SCRCs in MSI testing, forty-one were classified as MSI-High (MSI-H) and 3 as MSI-Low (MSI-L). MSI-H were seen in 24/29(82.76%), 5/5(100%), 25/29(86.20%) and 10/11(90.90%) SCRCs with loss expressions of MLH1, MSH2, PMS2 and MSH6, respectively.

Comparison between IHC and MSI
 CasesH-MSIL-MSIMSS
MLH1/PMS2242103
Only MLH13210
Only PMS24301
MSH2/MSH63300
Only MSH21100
Only MSH66510
MLH1/MSH61001
Loss of all1100
MMR-D433625
MMR-I1014295
Total144404100


Compared to MSI testing, the 2-antibodies immunohistochemical panel (PMS2 and MSH6) was an extremely sensitive (82.5%) and specific (94.2%), which was as good as 4-antibodies panel in screening DNA mismatch repair defects.
Conclusions: Our studies showed that the frequency of the replication error abnormalities appears lower in Chinese SCRCs compared with those reported in Western populations. The 2-antibodies immunohistochemical panel (PMS2 and MSH6) achieves good sensitivity and specificity as an alternative screening tool to detect MSI-H SCRCs.
Category: Gastrointestinal

Wednesday, March 6, 2013 9:30 AM

Poster Session V # 99, Wednesday Morning

 

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