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Clin Cancer Res. 2017 Sep 1;23(17):5246-5254. doi: 10.1158/1078-0432.CCR-16-2994. Epub 2017 May 18.

Can Microsatellite Status of Colorectal Cancer Be Reliably Assessed after Neoadjuvant Therapy?

Author information

1
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
2
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
4
Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
5
Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
7
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
8
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. EVilar@mdanderson.org.

Abstract

Purpose: 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.Experimental design: 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.Results: 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.Conclusions: 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. Clin Cancer Res; 23(17); 5246-54. ©2017 AACR.

PMID:
28522602
PMCID:
PMC6035875
DOI:
10.1158/1078-0432.CCR-16-2994
[Indexed for MEDLINE]
Free PMC Article

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