Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients.
Endometrial cancer is the most common cancer in women with Lynch syndrome. The identification of individuals with Lynch syndrome is desirable because they can benefit from increased cancer surveillance. The purpose of this study was to determine the feasibility and desirability of molecular screening for Lynch syndrome in all endometrial cancer patients. Unselected endometrial cancer patients (N = 543) were studied. All tumors underwent microsatellite instability (MSI) testing. Patients with MSI-positive tumors underwent testing for germ line mutations in MLH1, MSH2, MSH6, and PMS2. Of 543 tumors studied, 118 (21.7%) were MSI positive (98 of 118 MSI high and 20 of 118 MSI low). All 118 patients with MSI-positive tumors had mutation testing, and nine of them had deleterious germ line mutations (one MLH1, three MSH2, and five MSH6). In addition, one case with an MSI-negative tumor had abnormal MSH6 immunohistochemical staining and was subsequently found to have a mutation in MSH6. Immunohistochemical staining was consistent with the mutation result in all seven truncating mutation-positive cases but was not consistent in two of the three missense mutation cases. We conclude that in central Ohio, at least 1.8% (95% confidence interval, 0.9-3.5%) of newly diagnosed endometrial cancer patients had Lynch syndrome. Seven of the 10 Lynch syndrome patients did not meet any published criteria for hereditary nonpolyposis colorectal cancer, and six of them were diagnosed at age >50. Studying all endometrial cancer patients for Lynch syndrome using a combination of MSI and immunohistochemistry for molecular prescreening followed by gene sequencing and deletion analysis is feasible and may be desirable.
Hampel
Heather
H
Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, 420 West 12th Avenue, Columbus, OH 43210, USA.
Frankel
Wendy
W
Panescu
Jenny
J
Lockman
Janet
J
Sotamaa
Kaisa
K
Fix
Daniel
D
Comeras
Ilene
I
La Jeunesse
Jennifer
J
Nakagawa
Hidewaki
H
Westman
Judith A
JA
Prior
Thomas W
TW
Clendenning
Mark
M
Penzone
Pamela
P
Lombardi
Janet
J
Dunn
Patti
P
Cohn
David E
DE
Copeland
Larry
L
Eaton
Lynne
L
Fowler
Jeffrey
J
Lewandowski
George
G
Vaccarello
Luis
L
Bell
Jeffrey
J
Reid
Gary
G
de la Chapelle
Albert
A
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D019175:DNA Methylation; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008403:Mass Screening / Q000379:methods; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes