Universal Screening of Both Endometrial and Colon Cancers Increases the Detection of Lynch Syndrome

被引：73

作者：

Adar, Tomer ^{[1
]}

Rodgers, Linda H. ^{[2
]}

Shannon, Kristen M. ^{[2
]}

Yoshida, Makoto ^{[1
]}

Ma, Tianle ^{[1
]}

Mattia, Anthony ^{[3
,4
]}

Lauwers, Gregory Y. ^{[3
]}

Iafrate, Anthony J. ^{[3
]}

Hartford, Nicole M. ^{[3
]}

Oliva, Esther ^{[3
]}

Chung, Daniel C. ^{[1
,2
]}

机构：

[1] Harvard Med Sch, Massachusetts Gen Hosp, Div Gastroenterol, Dept Med, Boston, MA USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Risk Anal, Boston, MA USA

[3] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA

[4] North Shore Med Ctr, Dept Pathol, Danvers, MA USA

来源：

CANCER | 2018年 / 124卷 / 15期

关键词：

colorectal cancer; endometrial cancer; hereditary cancer syndromes; Lynch syndrome; universal screening; NONPOLYPOSIS COLORECTAL-CANCER; ACADEMIC-MEDICAL-CENTER; COST-EFFECTIVENESS; GERMLINE MUTATIONS; STRATEGIES; IMPLEMENTATION; IDENTIFICATION; FEASIBILITY; VALIDATION; GUIDELINES;

D O I：

10.1002/cncr.31534

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Screening of all CRCs for LS is currently recommended, but screening of ECs is inconsistent. The objective of this study was to determine the added value of screening both CRC and EC tumors in the same population. METHODS: A prospective, immunohistochemistry (IHC)-based screening program for all patients with newly diagnosed CRCs and ECs was initiated in 2011 and 2013, respectively, at 2 centers (primary and tertiary). Genetic testing was recommended for those who had tumors with absent mutS homolog 2 (MSH2), MSH6, or postmeiotoic segregation increased 2 (PMS2) expression and for those who had tumors with absent mutL homolog 1 (MLH1) expression and no v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation or MLH1 promoter methylation. Amsterdam II criteria, revised Bethesda criteria, and scores from prediction models for gene mutations (the PREMM1,2,6 and PREMM5 prediction models) were ascertained in patients with LS. RESULTS: In total, 1290 patients with CRC and 484 with EC were screened for LS, and genetic testing was recommended for 137 patients (10.6%) and 32 patients (6.6%), respectively (P=.01). LS was identified in 16 patients (1.2%) with CRC and in 8 patients (1.7%) with EC. Among patients for whom genetic testing was recommended, the LS diagnosis rate was higher among those with EC (25.0% vs 11.7%, P=.052). The Amsterdam II criteria, revised Bethesda criteria, and both PREMM calculators would have missed 62.5%, 50.0%, and 12.5% of the identified patients with LS, respectively. CONCLUSIONS: Expanding a universal screening program for LS to include patients who had EC identified 50% more patients with LS, and many of these patients would have been missed by risk assessment tools (including PREMM5). Universal screening programs for LS should include both CRC and EC. (C) 2018 American Cancer Society.

引用

页码：3145 / 3153

页数：9

共 30 条

[1] Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease [J].

Aaltonen, LA ;

Salovaara, R ;

Kristo, P ;

Canzian, F ;

Hemminki, A ;

Peltomäki, P ;

Chadwick, RB ;

Kääriäinen, H ;

Eskelinen, M ;

Järvinen, H ;

Mecklin, JP ;

de la Chapelle, A ;

Percesepe, A ;

Ahtola, H ;

Härkönen, N ;

Julkunen, R ;

Kangas, E ;

Ojala, S ;

Tulikoura, J ;

ValKamo, E .

NEW ENGLAND JOURNAL OF MEDICINE, 1998, 338 (21) :1481-1487

[2] 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

[3] Genetic Testing by Cancer Site Uterus [J].

Daniels, Molly S. .

CANCER JOURNAL, 2012, 18 (04) :338-342

[4] Performance Characteristics of Screening Strategies for Lynch Syndrome in Unselected Women With Newly Diagnosed Endometrial Cancer Who Have Undergone Universal Germline Mutation Testing [J].

Ferguson, Sarah E. ;

Aronson, Melyssa ;

Pollett, Aaron ;

Eiriksson, Lua R. ;

Oza, Amit M. ;

Gallinger, Steven ;

Lerner-Ellis, Jordan ;

Alvandi, Zahra ;

Bernardini, Marcus Q. ;

MacKay, Helen J. ;

Mojtahedi, Golnessa ;

Tone, Alicia A. ;

Massey, Christine ;

Clarke, Blaise A. .

CANCER, 2014, 120 (24) :3932-3939

[5] Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancere [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. .

AMERICAN JOURNAL OF GASTROENTEROLOGY, 2014, 109 (08) :1159-1179

[6] 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-+

[7] 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

[8] 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

[9] Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients [J].

Hampel, Heather ;

Frankel, Wendy ;

Panescu, Jenny ;

Lockman, Janet ;

Sotamaa, Kaisa ;

Fix, Daniel ;

Comeras, Ilene ;

La Jeunesse, Jennifer ;

Nakagawa, Hidewaki ;

Westman, Judith A. ;

Prior, Thomas W. ;

Clendenning, Mark ;

Penzone, Pamela ;

Lombardi, Janet ;

Dunn, Patti ;

Cohn, David E. ;

Copeland, Larry ;

Eaton, Lynne ;

Fowler, Jeffrey ;

Lewandowski, George ;

Vaccarello, Luis ;

Bell, Jeffrey ;

Reid, Gary ;

de la Chapelle, Albert .

CANCER RESEARCH, 2006, 66 (15) :7810-7817

[10] Feasibility of Screening for Lynch Syndrome Among Patients With Colorectal Cancer [J].

Hampel, Heather ;

Frankel, Wendy L. ;

Martin, Edward ;

Arnold, Mark ;

Khanduja, Karamjit ;

Kuebler, Philip ;

Clendenning, Mark ;

Sotamaa, Kaisa ;

Prior, Thomas ;

Westman, Judith A. ;

Panescu, Jenny ;

Fix, Dan ;

Lockman, Janet ;

LaJeunesse, Jennifer ;

Comeras, Ilene ;

de la Chapelle, Albert .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (35) :5783-5788

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