Universal screening of both endometrial and colon cancers increases the detection of Lynch syndrome

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 a...

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Bibliographic Details
Published in:Cancer 2018-08, Vol.124 (15), p.3145-3153
Main Authors: 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.
Format: Article
Language:English
Subjects:
Aged
Animal models
Biomarkers, Tumor - genetics
Calculators
Cancer
Colon
Colonic Neoplasms - diagnosis
Colonic Neoplasms - epidemiology
Colonic Neoplasms - genetics
Colonic Neoplasms - pathology
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis
Colorectal Neoplasms, Hereditary Nonpolyposis - epidemiology
Colorectal Neoplasms, Hereditary Nonpolyposis - genetics
Colorectal Neoplasms, Hereditary Nonpolyposis - pathology
Criteria
DNA methylation
DNA-Binding Proteins - genetics
Early Detection of Cancer - methods
Endometrial cancer
Endometrial Neoplasms - diagnosis
Endometrial Neoplasms - epidemiology
Endometrial Neoplasms - genetics
Endometrial Neoplasms - pathology
Endometrium
Female
Gene Expression Regulation, Neoplastic
Genetic disorders
Genetic screening
Genetic Testing
hereditary cancer syndromes
Homology
Humans
Immunohistochemistry
Lynch syndrome
Male
Mathematical models
Middle Aged
Mismatch Repair Endonuclease PMS2 - genetics
MLH1 protein
MSH2 protein
MSH6 protein
Mutation
MutL Protein Homolog 1 - genetics
MutS Homolog 2 Protein - genetics
Oncology
Patients
Prediction models
Risk assessment
Sarcoma
Screening
Software
Tumors
universal screening
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Summary: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. Cancer 2018. © 2018 American Cancer Society. A combined approach that includes both endometrial and colorectal tumors in a universal screening program for Lynch syndrome enhances the detection of families with Lynch syndrome compared with screening for colorectal cancer alone. This is the first prospective program to demonstrate the added value of this combined approach when both tumors are screened in the same population.
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.31534