Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer.

BACKGROUND: DNA mismatch repair system deficiency (dMMR) is found in 15% of colorectal cancers (CRCs). Two methods are used to determine dMMR, immunohistochemistry (IHC) of MMR proteins and molecular testing of microsatellite instability (MSI). Only studies with a low number of patients have reported rates of discordance between these two methods, ranging from 1% to 10%. MATERIALS AND METHODS: Overall, 3228 consecutive patients with CRCs from two centers were included. Molecular testing was carried out using the Pentaplex panel and IHC evaluated four (MLH1, MSH2, MSH6, and PMS2; cohort 1; n = 1085) or two MMR proteins (MLH1 and MSH2; cohort 2; n = 2143). The primary endpoint was the rate of discordance between MSI and MMR IHC tests. RESULTS: Fifty-one discordant cases (1.6%) were initially observed. Twenty-nine out of 51 discordant cases were related to IHC misclassifications. In cohort 1, after re-reading IHC and/or carrying out new IHC, 16 discordant cases were reclassified as nondiscordant. In cohort 2, after the addition of MSH6/PMS2 IHC and re-examination, 13 were reclassified as nondiscordant. In addition, 10 misclassifications of molecular tests were identified. Finally, only 12 discordant cases (0.4%) remained: 5 were proficient MMR/MSI and 7 were dMMR/microsatellite stable. CONCLUSIONS: Our study confirmed the high degree of concordance between MSI and MMR IHC tests. Discordant cases must be reviewed, and if needed, tests must be repeated and analyzed by an expert team.

[Preoperative intensity-modulated radiotherapy of rectal cancers: Relevance and modalities]. / Radiothérapie avec modulation d'intensité préopératoire des cancers rectaux : intérêt et application.

Preoperative radiotherapy boosted by chemotherapy is a recommended treatment in locally advanced rectal cancers. This treatment is delivered by three dimensional conformal irradiation, which is usually well tolerated but can induce potential toxicity such as rectitis, cystitis and hematologic adverse effects. Intensity-modulated radiotherapy, widely available nowadays, allows optimization of volume covering and sparing of organs at risk such as bladder and bone marrow. This review presents relevant clinical situations and requirements for a beneficial and safe preoperative irradiation of rectal cancers by intensity-modulated technique. This technique is compared to three-dimensional conformal radiotherapy.