29 June 2023
: Case report 
Endometrial Adenocarcinoma with Discordant Microsatellite Stability Status Treated with First-Line Pembrolizumab: A Case Report and Narrative Review
Unusual clinical course, Challenging differential diagnosis, Unusual or unexpected effect of treatment, Rare coexistence of disease or pathology
Christopher R. Grant1ABCDEF*, Elaine J. Chiao1EF, Zhaohui L. Arter2ADE, Cary Johnson3C, Truc Tran3BE, Farshid Dayyani2E, Krishnasu Tewari2E, Valery Vilchez4E, Joseph Carmichael
4E, May Cho2ABCDE
DOI: 10.12659/AJCR.939448
Am J Case Rep 2023; 24:e939448
Table 3. Studies regarding discordance of Immunohistochemistry and PCR/Next-Generation Sequencing in various carcinomas.
| Case study | Type of study | Number of cases | Population | Aim | Discordance rates | Conclusion |
|---|---|---|---|---|---|---|
| Cohen et al [], 201820 | Multicenter retrospective analysis | 92 | Colorectal carcinoma, multicenter retrospective analysis | Evaluate accuracy of standard IHC and PCR methods in detection of MSI status in mCRC | 9.1% | Local assessment of MSI/dMMR status resulted in misdiagnosis of 9.1% cases as false positive and dual testing should be heavily considered |
| Zheng et al [], 202021 | Tumor and paired control samples | 64 | Colorectal carcinoma, one academic center | 9-loci model able to detect MSI status compared to MSI-PCR and IHC staining | 15.7% | Microsatellite loci detects MSI status with 100% sensitivity and specificity in samples with concordant MSI/IHC status |
| Kim et al [], 202022 | Prospective paired analysis | 30 | Endometrial and ovarian carcinoma | Examine concordance in MMR expression between tumor sites in synchronous endometrial and ovarian cancer | 7% | Incidence of MSI was high in women with synchronous endometrial cancer |
| Guyot D’Asinieres De Salins et al [], 202129 | Retrospective database analysis | 1085 | Colorectal carcinoma, two academic centers France | Determine rate of discordance between pentaplex NGS panel and IHC | 1.6% | High degree of concordance between MSI and MMR IHC testing and discordant cases can potentially be repeated |
| Amemiya et al [], 202223 | Paired analysis prospective study | 284 | 14 cancer types | IHC more suitable for evaluating MMR status in a tumor | 1.9% | IHC is the best choice in determining MMR alterations |
| Stello et al [], 201724 | Retrospective database analysis | 854 | Endometrial carcinoma | Define optimal approach for MMR-Def testing and to clarify discrepancies between MSI analysis and IHC analysis of MMR protein expression | 14.6% | MSI and IHC are highly concordant in endometrial cancer with discordant results explained by POLE-EDM variants |
| Loughrey et al [], 202025 | Retrospective database analsysis | 661 | Colorectal cancer | Compare PCR-based testing and IHC in stage 2 and 3 colon cancer cases in Northern Ireland | 2.9% | MSI-PCR testing and MMR IHC can be considered to be equally proficient tests for establishing MMR/MSI status |
| Park et al [], 202126 | Retrospective cohort analysis | 8229 | Gastric cancer and colorectal cancer | Determine the clinical utility of IHC and PCR in colorectal cancer and gastric cancer | 1.0% | With the low incidence of discordance, this provides evidence for MSI testing and MMR IHC in routine clinical practice |
| Hechtman et al [], 202027 | Retrospective database analysis | 443 | 32 various tumors | Determine the underlying cause of discordant microsatellite testing | 7.2% | Retained mismatch repair protein expression occurs in 6% of MSI-H while MSI-H harbor isolated loss of the defective mismatch repair gene’s dimerization partner |
| Bartley et al [], 201228 | Retrospective database analysis | 591 | Colorectal and endometrial cancer | Can IHC and MSI analysis both be used to evaluate patients with cancer for lynch syndrome | 3.9% | IHC by itself as a screen is the failure to identify colorectal and endometrial cancer patients who likely have Lynch syndrome |