Should you repeat mismatch repair testing in cases of tumour recurrence? An evaluation of repeat mismatch repair testing by the use of immunohistochemistry in recurrent tumours of the gastrointestinal and gynaecological tracts

被引:6
作者
Aird, John J. [1 ,2 ]
Steel, Michael J. [1 ]
Chow, Christine [3 ]
Ho, Julie [4 ]
Wolber, Robert [5 ]
Gilks, C. Blake [1 ,2 ]
Hoang, Lynn N. [1 ,2 ]
Schaeffer, David F. [1 ,2 ]
机构
[1] Vancouver Gen Hosp, Div Anat Pathol, 899 W 12th Ave, Vancouver, BC V5Z 1M9, Canada
[2] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada
[3] Jack Bell Res Ctr, Genet Pathol Evaluat Ctr, Vancouver, BC, Canada
[4] British Columbia Canc Agcy, Dept Mol Oncol, Vancouver, BC, Canada
[5] Lions Gate Hosp, Dept Lab Med & Pathol, N Vancouver, BC, Canada
关键词
DNA mismatch repair; endometrial carcinoma; gastrointestinal cancer; immunohistochemistry; COLORECTAL-CANCER PATIENTS; LYNCH SYNDROME; MICROSATELLITE INSTABILITY; CONCORDANCE; METASTASES; PATHOLOGY; THERAPY; SOCIETY;
D O I
10.1111/his.14026
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aims The role of mismatch repair (MMR) testing has evolved from identifying Lynch syndrome patients to predicting response to immune checkpoint inhibitors. This has led to requests from clinicians to retest recurrences of MMR-proficient primary tumours in the hope that the recurrence may show a different MMR status and qualify the patient for treatment. We aimed to determine whether repeat testing is warranted. Methods and results We evaluated recurrent tumours (local recurrences or metastases) from 137 patients with MMR-proficient primary tumours of the gastrointestinal and gynaecological tracts. The local recurrences and metastases all occurred at least 30 days after resection of the primary tumour. We used a combination of a tissue microarray and whole slide staining to perform immunohistochemistry (IHC) for PMS2, MLH1, MSH2, and MSH6, and compared the results with the MMR status of the primary tumour. Three of 137 (2%) initially showed a discordant staining pattern. However, further investigation showed that these discordances were attributable to some of the known pitfalls associated with MMR IHC interpretation - post-radiotherapy loss of MSH6 expression and subclonal loss of MLH1 staining. We did not identify any cases with a genuine discordance in MMR status. Conclusion We conclude that repeat MMR IHC testing of recurrences is not warranted, as MMR status does not change relative to that of the primary tumour.
引用
收藏
页码:521 / 530
页数:10
相关论文
共 31 条
[1]   A tailored approach to BRAF and MLH1 methylation testing in a universal screening program for Lynch syndrome [J].
Adar, Tomer ;
Rodgers, Linda H. ;
Shannon, Kristen M. ;
Yoshida, Makoto ;
Ma, Tianle ;
Mattia, Anthony ;
Lauwers, Gregory Y. ;
Iafrate, Anthony J. ;
Chung, Daniel C. .
MODERN PATHOLOGY, 2017, 30 (03) :440-447
[2]  
[Anonymous], 2014, Obstet Gynecol, V124, P1042, DOI 10.1097/01.AOG.0000456325.50739.72
[3]   Concordance of Predictive Markers for EGFR Inhibitors in Primary Tumors and Metastases in Colorectal Cancer: A Review [J].
Baas, Jara M. ;
Krens, Lisanne L. ;
Guchelaar, Henk-Jan ;
Morreau, Hans ;
Gelderblom, Hans .
ONCOLOGIST, 2011, 16 (09) :1239-1249
[4]   Neoadjuvant Therapy Induces Loss of MSH6 Expression in Colorectal Carcinoma [J].
Bao, Fei ;
Panarelli, Nicole C. ;
Rennert, Hanna ;
Sherr, David L. ;
Yantiss, Rhonda K. .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2010, 34 (12) :1798-1804
[5]   Analysis of the Concordance in the EGFR Pathway Status Between Primary Tumors and Related Metastases of Colorectal Cancer Patients: Implications for Cancer Therapy [J].
Cejas, P. ;
Lopez-Gomez, M. ;
Aguayo, C. ;
Madero, R. ;
Moreno-Rubio, J. ;
de Castro Carpeno, J. ;
Belda-Iniesta, C. ;
Barriuso, J. ;
Moreno Garcia, V. ;
Diaz, E. ;
Burgos, E. ;
Gonzalez-Baron, M. ;
Feliu, J. .
CURRENT CANCER DRUG TARGETS, 2012, 12 (02) :124-131
[6]  
CHEN W, 2019, MODERN PATHOL S, V32
[7]   Association of Primary Resistance to Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer With Misdiagnosis of Microsatellite Instability or Mismatch Repair Deficiency Status [J].
Cohen, Romain ;
Hain, Elisabeth ;
Buhard, Olivier ;
Guilloux, Agathe ;
Bardier, Armelle ;
Kaci, Rachid ;
Bertheau, Philippe ;
Renaud, Florence ;
Bibeau, Frederic ;
Flejou, Jean-Francois ;
Andre, Thierry ;
Svrcek, Magali ;
Duval, Alex .
JAMA ONCOLOGY, 2019, 5 (04) :551-555
[8]   Genomics of response to immune checkpoint therapies for cancer: implications for precision medicine [J].
Conway, Jake R. ;
Kofman, Eric ;
Mo, Shirley S. ;
Elmarakeby, Haitham ;
Van Allen, Eliezer .
GENOME MEDICINE, 2018, 10
[9]   High concordance rate of KRAS/BRAF mutations. and MSI-H between primary colorectal cancer and corresponding metastases [J].
Fujiyoshi, Kenji ;
Yamamoto, Gou ;
Takahashi, Akemi ;
Arai, Yoshiko ;
Yamada, Mina ;
Kakuta, Miho ;
Yamaguchi, Kensei ;
Akagi, Yoshito ;
Nishimura, Yoji ;
Sakamoto, Hirohiko ;
Akagi, Kiwamu .
ONCOLOGY REPORTS, 2017, 37 (02) :785-792
[10]   Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer [J].
Giardiello, Francis M. ;
Allen, John I. ;
Axilbund, Jennifer E. ;
Boland, C. Richard ;
Burke, Carol A. ;
Burt, Randall W. ;
Church, James M. ;
Dominitz, Jason A. ;
Johnson, David A. ;
Kaltenbach, Tonya ;
Levin, Theodore R. ;
Lieberman, David A. ;
Robertson, Douglas J. ;
Syngal, Sapna ;
Rex, Douglas K. .
DISEASES OF THE COLON & RECTUM, 2014, 57 (08) :1025-1048