Case-case study of factors associated to hMLH1, hMSH2, and hMSH6 protein expression among endometrial cancer patients of the University District Hospital of San Juan, Puerto Rico.
Lynch syndrome (LS) is an autosomal dominant disorder caused by DNA mismatch repair (MMR) system deficiencies. Women affected by LS present a 40% to 60% lifetime risk of endometrial cancer (EC).


OBJECTIVE
This case-case study aims to determine the frequency of the hMLH1, hMSH2, and hMSH6 MMR proteins and the factors (age, family history of cancer [FHC] related to LS, and body mass index [BMI]) associated to their absence in EC patients attending the University District Hospital of San Juan, Puerto Rico.


METHODS
Twenty cases were preliminary evaluated for the MMR protein expression by immunohistochemistry testing and classified as positive cases (presence of protein) or negative cases (absence of protein). The statistical analysis was based on the logistic regression model using the maximum likelihood estimation (MLE). The Bayesian approach was used to determine the posterior probability (posterior Pr[odds ratio {OR} > 1]).


RESULTS
Results showed absence for at least 1 MMR protein in 25% of the cases, 15% for hMLH1, and 10% for hMSH2. None of the cases showed an absence for hMSH6. The MLE demonstrated that women diagnosed with EC before the age of 50 (OR: 12.4; 95% confidence interval [CI] = 0.5-322.7), having FHC related to LS (OR: 17.7; 95% CI = 0.6-534.6), and having lower BMI (OR: 2.38; 95% CI = 0.39-14.28) present higher odds than their counterparts of lacking an MMR protein, once adjusted for potential predictors (P > 0.05). The posterior probability that an excess risk of lacking an MMR protein occurs was 95% or greater for each predictor.


CONCLUSIONS
Our study in this Hispanic population supports previous studies in that younger age, FHC, and lower BMI are associated with increased odds of having an absence of MMR protein expression. Further studies with larger sample sizes should be performed.
Department of Biostatistics and Epidemiology, Graduate School of Public Health, MSC-UPR, San Juan, Puerto Rico.
Lorena
L
González
Ana P
AP
Ortiz
Erick L
EL
Suárez
Sharee
S
Umpierre
Jorge
J
Billoch
Maria J
MJ
Marcos
Leilani
L
Joy
Eileen
E
Charneco
Mercedes Y
MY
Lacourt
Raúl D
RD
Bernabe-Dones
Marcia R
MR
Cruz-Correa
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015992:Body Mass Index; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D011647:Puerto Rico
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein