A simplified two-marker immunohistochemistry strategy for Lynch syndrome screening in endometrial cancer patients

被引：1

作者：

Aiob, Ala ^{[1
]}

Kim, Yeo Rae ^{[2
]}

Kim, Kidong ^{[2
]}

Kim, Hyojin ^{[3
]}

Kim, Yong Beom ^{[2
]}

Kim, Duck Woo ^{[4
]}

No, Jae Hong ^{[2
]}

Seo, Soo Hyun ^{[5
]}

Suh, Dong Hoon ^{[2
]}

Park, Kyoung Un ^{[5
]}

机构：

[1] Bar Ilan Univ, Azrieli Fac Med, Galilee Med Ctr, Dept Obstet & Gynecol, Safed, Israel

[2] Seoul Natl Univ, Coll Med, Bundang Hosp, Dept Obstet & Gynecol, 82 Gumi Ro,173beon Gil, Seongnam 13620, South Korea

[3] Seoul Natl Univ, Coll Med, Bundang Hosp, Dept Pathol, Seongnam, South Korea

[4] Seoul Natl Univ, Coll Med, Dept Surg, Bundang Hosp, Seongnam, South Korea

[5] Seoul Natl Univ, Bundang Hosp, Dept Lab Med, Coll Med, Seongnam, South Korea

来源：

OBSTETRICS & GYNECOLOGY SCIENCE | 2023年 / 66卷 / 06期

关键词：

Lynch syndrome II; Mass screening; G-T mismatch-binding protein; Immunohistochemistry; CLINICAL-PRACTICE; GUIDELINES;

D O I：

10.5468/ogs.23124

中图分类号：

R71 [妇产科学];

学科分类号：

100211 ;

摘要：

Objective To examine the efficacy of MSH6 and PMS2 immunohistochemistry (IHC) as a screening method for Lynch syndrome in endometrial cancer patients. Methods Through multidisciplinary discussions, an institutional MSH6 and PMS2 IHC-initiated cascade test (MSH6, PMS2 IHC-microsatellite instability [MSI] assay-germline mismatch repair [MMR] gene sequencing) was developed to screen for Lynch syndrome in endometrial cancer patients. Testing was performed on a consecutive cohort of 218 newly diagnosed endometrial cancer patients who underwent surgery at a tertiary hospital in the Republic of Korea between August 2018 and December 2020. The number of MMR deficiencies (MSH6 or PMS2 loss in IHC) and results of subsequent tests (MSI assay and germline MMR gene sequencing) were examined. Results MMR deficiency was detected in 52 of the 218 patients (24.0%). Among these 52 patients, 34 (65.0%) underwent MSI testing, of which 31 (91.0%) exhibited high MSI. Of the 31 patients with MSI-high status, 15 (48.0%) underwent germline MMR gene sequencing. Subsequently, Lynch syndrome was diagnosed in five patients (33.0%). Conclusion Lynch syndrome screening using MSH6 and PMS2 IHC-initiated cascade testing is a viable strategy in the management of endometrial cancer. A simplified strategy (MSH6 and PMS2 IHC-germline MMR gene sequencing) was proposed because most women with MMR deficiencies exhibited high MSI.

引用

页码：537 / 544

页数：8

共 26 条

[1] Universal Screening of Both Endometrial and Colon Cancers Increases the Detection of Lynch Syndrome [J].

Adar, Tomer ;

Rodgers, Linda H. ;

Shannon, Kristen M. ;

Yoshida, Makoto ;

Ma, Tianle ;

Mattia, Anthony ;

Lauwers, Gregory Y. ;

Iafrate, Anthony J. ;

Hartford, Nicole M. ;

Oliva, Esther ;

Chung, Daniel C. .

CANCER, 2018, 124 (15) :3145-3153

[2] Three molecular pathways model colorectal carcinogenesis in Lynch syndrome [J].

Ahadova, Aysel ;

Gallon, Richard ;

Gebert, Johannes ;

Ballhausen, Alexej ;

Endris, Volker ;

Kirchner, Martina ;

Stenzinger, Albrecht ;

Burn, John ;

Doeberitz, Magnus von Knebel ;

Blaeker, Hendrik ;

Kloor, Matthias .

INTERNATIONAL JOURNAL OF CANCER, 2018, 143 (01) :139-150

[3] Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations [J].

Barrow, E. ;

Robinson, L. ;

Alduaij, W. ;

Shenton, A. ;

Clancy, T. ;

Lalloo, F. ;

Hill, J. ;

Evans, D. G. .

CLINICAL GENETICS, 2009, 75 (02) :141-149

[4] Comparison of screening strategies for Lynch syndrome in patients with newly diagnosed endometrial cancer: a prospective cohort study in China [J].

Chao, Xiaopei ;

Li, Lei ;

Wu, Ming ;

Ma, Shuiqing ;

Tan, Xianjie ;

Zhong, Sen ;

Bi, Yalan ;

Lang, Jinghe .

CANCER COMMUNICATIONS, 2019, 39

[5] The genetic basis of Lynch syndrome and its implications for clinical practice and risk management [J].

Cohen, Stephanie A. ;

Leininger, Anna .

APPLICATION OF CLINICAL GENETICS, 2014, 7 :147-158

[6] Current Lynch Syndrome Tumor Screening Practices: A Survey of Genetic Counselors [J].

Cohen, Stephanie A. .

JOURNAL OF GENETIC COUNSELING, 2014, 23 (01) :38-47

[7] Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study [J].

Goodfellow, Paul J. ;

Billingsley, Caroline C. ;

Lankes, Heather A. ;

Ali, Shamshad ;

Cohn, David E. ;

Broaddus, Russell J. ;

Ramirez, Nilsa ;

Pritchard, Colin C. ;

Hampel, Heather ;

Chassen, Alexis S. ;

Simmons, Luke V. ;

Schmidt, Amy P. ;

Gao, Feng ;

Brinton, Louise A. ;

Backes, Floor ;

Landrum, Lisa M. ;

Geller, Melissa A. ;

DiSilvestro, Paul A. ;

Pearl, Michael L. ;

Lele, Shashikant B. ;

Powell, Matthew A. ;

Zaino, Richard J. ;

Mutch, David .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (36) :4301-+

[8] Cost-effectiveness of routine screening for Lynch syndrome in endometrial cancer patients up to 70 years of age [J].

Goverde, Anne ;

Spaander, Manon C. W. ;

van Doom, Helena C. ;

Dubbink, Hendrikus J. ;

van den Ouweland, Ans M. W. ;

Tops, Carli M. ;

Kooi, Sjarlot G. ;

de Waard, Judith ;

Hoedemaeker, Robert F. ;

Bruno, Marco J. ;

Hofstra, Robert M. W. ;

de Bekker-Grob, Esther W. ;

Dinjens, Winand N. M. ;

Steyerberg, Ewout W. ;

Wagner, Anja .

GYNECOLOGIC ONCOLOGY, 2016, 143 (03) :453-459

[9] The incidence and survival of cervical, ovarian, and endometrial cancer in Korea, 1999-2017: Korea Central Cancer Registry [J].

Ha, Hyeong In ;

Chang, Ha Kyun ;

Park, Soo Jin ;

Lim, Jiwon ;

Won, Young-Joo ;

Lim, Myong Cheol .

OBSTETRICS & GYNECOLOGY SCIENCE, 2021, 64 (05) :444-453

[10] Screening for the Lynch syndrome (Hereditary nonpolyposis colorectal cancer). [J].

Hampel, H ;

Frankel, WL ;

Martin, E ;

Arnold, M ;

Khanduja, K ;

Kuebler, P ;

Nakagawa, H ;

Sotamaa, K ;

Prior, TW ;

Westman, J ;

Panescu, J ;

Fix, D ;

Lockman, J ;

Comeras, I ;

de la Chapelle, A ;

Ellison, C ;

Melvin, S ;

Winston, J ;

Adeli, A ;

Burak, W ;

Chadwick, R ;

Elkhatib, I ;

Hemingway, T ;

Jamieson, K ;

Johnson, C ;

LaJeunesse, J ;

Liyanarachchi, S ;

Rangel, P ;

Soble, D ;

Walker, M ;

Wise, T ;

Zhang, Y ;

Schlanger, R ;

Aguilar, P ;

Hura, D ;

Keith, J ;

Kerner, B ;

Lavalle, G ;

Taylor, C ;

Vara, T ;

Zangmeister, J ;

DeVictor, S ;

Hines, L ;

Lindsey, M ;

Madhavan, J ;

Padmanabhan, A ;

Hamelberg, K ;

Niemann, T ;

Behrens, BC ;

Blair, SC .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (18) :1851-1860

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