Mismatch repair protein expression in 1049 endometrial carcinomas, associations with body mass index, and other clinicopathologic variables.
OBJECTIVE
Links between obesity, with its attendant estrogen abnormalities, and the endometrial carcinoma (EC) DNA Mismatch Repair Protein (MMR) system have recently been proposed. We investigated relationships between body mass index (BMI) and clinicopathological correlates including MMR expression in a large single institution EC cohort.


METHODS
Clinical and pathological databases from 2007 to 2012 were used to identify consecutive hysterectomy specimens with EC. Univariate and multivariate analyses were used to explore relationships between BMI, age, stage, tumor type and immunohistochemical results for MLH1, PMS2, MSH2 and MSH6.


RESULTS
1049 EC were identified. Overall, BMI was higher amongst women with normal MMR (p=0.002). However, when stratified by age and specific MMR, statistically significant differences localized exclusively to women <50years old with loss of MSH2 and/or MSH6 (p=0.003 and p=0.005 respectively). Higher BMI correlated with endometrioid FIGO 1 and 2 tumors (p<0.001) and with stage 1a (p<0.001). Conversely, MMR abnormalities did not show significant associations with stage (p=0.302) or histologic grade (p=0.097).


CONCLUSIONS
BMI showed statistically significant associations with MMR expression, tumor grade and stage amongst 1049 consecutive EC. Obesity correlates with lower grade and stage EC. A link between BMI and maintenance of the MMR system is not supported by our data because the only statistically significant association occurred in women <50years old with MSH2 and/or MSH6 abnormalities where Lynch syndrome related cases are expected to cluster.
Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA.
Amy S
AS
Joehlin-Price
Department of Pathology and Immunology, Washington University in Saint Louis, Saint Louis, MO, USA.
Carmen M
CM
Perrino
Center of Biostatistics, The Ohio State University, Columbus, OH, USA.
Julie
J
Stephens
Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH, USA.
Floor J
FJ
Backes
Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH, USA.
Paul J
PJ
Goodfellow
Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH, USA.
David E
DE
Cohn
Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address: Adrian.Suarez@osumc.edu.
Adrian A
AA
Suarez
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D018262:Adenocarcinoma, Clear Cell / Q000150:complications / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015992:Body Mass Index; D002277:Carcinoma / Q000150:complications / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000150:complications / Q000378:metabolism*; D002296:Carcinosarcoma / Q000150:complications / Q000378:metabolism; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D015999:Multivariate Analysis; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D050177:Overweight / Q000150:complications / Q000378:metabolism; D012189:Retrospective Studies
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; 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
BMI; Body mass index; DNA mismatch repair protein; Endometrial cancer; MMR