Clinicopathologic significance of DNA mismatch repair protein defects and endometrial cancer in women 40 years of age and younger
ABSTRACT The hereditary basis of endometrial cancer is apparent in young women with endometrial cancer. The objective of this study was to examine risk factors and outcomes in patients 40 years of age and younger with endometrial cancer.
We performed a retrospective cohort study of patients aged 40 years or less who were diagnosed with endometrial carcinoma between 1/93 and 5/08. Clinical and pathologic data were extracted from medical records. Paraffin-embedded slides from hysterectomy specimens were obtained and DNA mismatch repair (MMR) immunohistochemistry was performed. Cases were analyzed according to the presence of DNA MMR protein defects. Standard two-sided statistical tests were performed.
Of the 56 identified patients, the median age was 36 years (range, 24-40). The majority of the endometrial carcinomas were of endometrioid histology (91%), stage I (71%), and FIGO grade 1 (59%). Abnormal DNA MMR was found in 9 cases (16%). Cases with abnormal DNA MMR had lower body mass index (BMI) (P=0.05), and had a family history suggestive of Lynch syndrome (P=0.001). Tumors were more likely to have advanced stage disease (P<0.001), be high grade (P<0.001), have deep myometrial invasion (P<0.001), and have lymphovascular invasion (P=0.002). Cases with abnormal DNA MMR had significantly worse overall survival (P=0.028) and progression-free survival (P=0.042).
Endometrial cancer is rare in women aged 40 years or less. In this group of patients, loss of DNA MMR was associated with lower BMI, worse clinicopathologic factors, and worse outcome. These results may have implications when young women diagnosed with endometrial cancer are counseled regarding prognosis.
- Viszeralmedizin / Visceral Medicine 01/2011; 27(4). DOI:10.1159/000331246 · 0.10 Impact Factor
Article: Endometrial cancer[Show abstract] [Hide abstract]
ABSTRACT: Endometrial carcinoma is the most common gynaecological malignancy in the Western world. The standard management of endometrial carcinoma is total hysterectomy and bilateral salpingo-oophorectomy with or without pelvic and para-aortic lymph-node dissection. Increasingly, endometrial cancer is being diagnosed in younger women in whom preserving fertility may be an important consideration when deciding optimal management. Conservative management of endometrial carcinoma may be a therapeutic option in carefully selected women with well-differentiated endometrial cancer in the absence of any myometrial invasion or adnexal disease seen on imaging. The biggest concern with conservative management of endometrial carcinoma is disease progression while on treatment or after initial response to medical treatment. Women opting for conservative management should be aware that hormonal therapy is not the standard form of management. Potential adverse outcomes should be taken into consideration.Best practice & research. Clinical obstetrics & gynaecology 01/2012; 26(3):311-24. DOI:10.1016/j.bpobgyn.2011.12.007 · 3.00 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Purpose:Lynch syndrome accounts for 2-5% of endometrial cancer cases. Lynch syndrome prediction models have not been evaluated among endometrial cancer cases.Methods:Area under the receiver operating curve (AUC), sensitivity and specificity of PREMM(1,2,6), MMRpredict, and MMRpro scores were assessed among 563 population-based and 129 clinic-based endometrial cancer cases.Results:A total of 14 (3%) population-based and 80 (62%) clinic-based subjects had pathogenic mutations. PREMM(1,2,6), MMRpredict, and MMRpro were able to distinguish mutation carriers from noncarriers (AUC of 0.77, 0.76, and 0.77, respectively), among population-based cases. All three models had lower discrimination for the clinic-based cohort, with AUCs of 0.67, 0.64, and 0.54, respectively. Using a 5% cutoff, sensitivity and specificity were as follows: PREMM(1,2,6), 93% and 5% among population-based cases and 99% and 2% among clinic-based cases; MMRpredict, 71% and 64% for the population-based cohort and 91% and 0% for the clinic-based cohort; and MMRpro, 57% and 85% among population-based cases and 95% and 10% among clinic-based cases.Conclusion:Currently available prediction models have limited clinical utility in determining which patients with endometrial cancer should undergo genetic testing for Lynch syndrome. Immunohistochemical analysis and microsatellite instability testing may be the best currently available tools to screen for Lynch syndrome in endometrial cancer patients.Genet Med advance online publication 8 March 2012.Genetics in medicine: official journal of the American College of Medical Genetics 03/2012; 14(7):670-80. DOI:10.1038/gim.2012.18 · 6.44 Impact Factor