Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Clin Cancer Res. 2017 Sep 1;23(17):5246-5254. doi: 10.1158/1078-0432.CCR-16-2994. Epub 2017 May 18.
Determination of microsatellite instability (MSI) by PCR is the gold standard; however, IHC of mismatch repair (MMR) proteins is frequently performed instead. The reliability of these methods on postneoadjuvant therapy specimens is unknown. We examined the effect of neoadjuvant therapy on MSI results by PCR and IHC. A total of 239 colorectal cancers resected after neoadjuvant therapy were assessed for MSI with PCR and IHC. PCR and IHC results for matched paired pre- and posttreatment specimens were compared. In parallel, 2 isogenic cell lines conditioned for MMR functioning and 2 different patient-derived xenografts (PDXs) were exposed to chemotherapy, radiation, or both. We also examined whether establishment of PDXs induced MSI changes in 5 tumors. IHC and MSI were tested after treatment to assess for changes. We identified paired pre- and posttreatment specimens for 37 patients: 2 with PCR only, 34 with IHC only, and 1 with both. All 3 patients with PCR had microsatellite stable pre- and posttreatment specimens. Of the 35 patients with IHC, 30 had intact MMR proteins in pre- and posttreatment specimens, 1 had equivocal MLH1 staining in the pretreatment and loss in the posttreatment specimen, and 4 had intact pretreatment MSH6 but variable posttreatment staining. In the experimental setting, no changes in MSI status were detected after treatment or tumor implantation in animals. Our findings show that the expression of MMR proteins, commonly MSH6, can change after neoadjuvant therapy and confirm PCR as the gold-standard test for MSI after neoadjuvant therapy. .
通过聚合酶链反应（PCR）测定微卫星不稳定性（MSI）是金标准；然而，经常替代它的是错配修复（MMR）蛋白的免疫组织化学（IHC）检测。这些方法在新辅助治疗后标本上的可靠性是未知的。我们通过 PCR 和 IHC 检测新辅助治疗对 MSI 结果的影响。对 239 例接受新辅助治疗后切除的结直肠癌患者进行 MSI 检测，包括聚合酶链反应和免疫组织化学。比较了配对的治疗前后标本的 PCR 和 IHC 结果。同时，我们对 2 种经过 MMR 功能调节的同基因细胞系和 2 种不同的患者来源异种移植瘤（PDX）进行了化疗、放疗或两者联合治疗。我们还检查了 5 个肿瘤的 PDX 建立是否诱导 MSI 改变。治疗后进行 IHC 和 MSI 检测以评估变化。我们鉴定了 37 例患者的配对治疗前后标本：2 例仅行 PCR，34 例仅行 IHC，1 例同时行 PCR 和 IHC。所有 3 例 PCR 患者的治疗前后标本均为微卫星稳定。35 例 IHC 患者中，30 例治疗前后标本 MMR 蛋白完整，1 例治疗前 MLH1 染色不确定，治疗后丢失，4 例治疗前 MSH6 完整，但治疗后染色可变。在实验环境中，动物治疗或肿瘤植入后未检测到 MSI 状态的变化。我们的研究结果表明，MMR 蛋白的表达，通常是 MSH6，在新辅助治疗后可能发生改变，并证实 PCR 是新辅助治疗后 MSI 的金标准检测。
