Search

Although consensus has yet to be reached on universal mismatch-repair (MMR) protein immunohistochemical (IHC) screening for Lynch syndrome (LS) in endometrial cancer (EC), an increasing number of institutions have adopted universal screening protocols similar to those used for colorectal carcinoma. Here we describe our institution's experience with a prospective universal screening protocol in which all ECs resected over a period of 19 months (n=242) were screened for MLH1, PMS2, MSH2, and MSH6 deficiencies using IHC, followed by MLH1 promoter methylation testing when appropriate. When consent was obtained, tumor samples underwent next-generation sequencing. A total of 11 unmethylated MMR-deficient cases (4.5% of cohort) were identified through IHC screening. Germline testing was performed in 10 cases and confirmed LS in 4 patients (1.7% of cohort). Of our 4 confirmed LS cases, 1 did not meet traditional LS screening criteria (eg, age below 50 y, Revised Bethesda criteria). In addition, universal screening identified 6 germline-negative MMR-deficient nonmethylated cases, 4 of which occurred in women older than 50. Although our next-generation sequencing data suggest somatic mutations in 4 of these cases, it is possible that these cases may represent cases of "Lynch-like syndrome." We conclude that a subset of LS cases could be missed using traditional screening guidelines. The value of screening for Lynch-like syndrome has yet to be determined. Although the cost-effectiveness of universal screening in EC has yet to be elucidated, we conclude that universal IHC screening is currently a reasonable, and arguably superior, approach to screening for LS.

To examine hysterectomies in the United States performed for gynecologic malignancies and identify factors associated with the use of minimally invasive techniques.This is a cross-sectional analysis of the 2012 National Inpatient Sample, the largest national all-payer database of hospital discharges. International Classification of Diseases, 9th Revision, Clinical Modification codes for any type of hysterectomy performed for gynecologic malignancy were used to abstract pertinent observations. Weighted multivariable logistic regression models were used to examine the associations between demographic and clinical factors and mode of hysterectomy by cancer diagnosis.In 2012, there were an estimated 46,450 hysterectomies for gynecologic malignancy in the United States. Of these, 28,285 (61%) were performed for uterine, 4,275 (9%) for cervical, 12,370 (27%) for ovarian cancer, and 1,520 (3%) for other gynecologic malignancies. Minimally invasive hysterectomy was used in 50% of uterine, 43% of cervical, and 8.5% of ovarian cancer cases. Black women had decreased odds of undergoing minimally invasive hysterectomy for uterine (adjusted odds ratio [OR] 0.50, 95% confidence interval [CI] 0.40-0.0.63, P.001) and cervical (adjusted OR 0.56, 95% CI 0.33-0.96, P=.03) cancers. Those without insurance or with Medicaid had decreased odds of undergoing minimally invasive hysterectomy (P.001) for uterine cancer. As compared with the Northeast, patients in the South (adjusted OR 0.72, 95% CI 0.53-0.98, P=.04) were less likely to undergo minimally invasive hysterectomy for uterine cancer, whereas those in the West more likely (adjusted OR 1.48, 95% CI 1.10-1.99, P=.009).Minimally invasive hysterectomy for gynecologic malignancies remained underused in 2012; there were striking racial disparities associated with use of minimally invasive hysterectomy for uterine and cervical cancers.III.

BACKGROUND: Phytoestrogens are increasingly used by patients as “natural” alternatives to hormone replacement. Attention in scientific and lay literature has focused on their potential to prevent menopausal symptoms, bone loss, heart disease, or breast cancer. Less is known about effects on the endometrium, specifically, whether prolonged exposure to phytoestrogens could promote hyperplasia or neoplasia, as does unopposed estrogen. CASE: We report the case of a woman diagnosed with grade 1 endometrioid adenocarcinoma of the endometrium whose history was notable for extensive use of supplemental phytoestrogens. CONCLUSION: The effects of phytoestrogens on endometrial tissue are not known. Given their increasing popularity and availability in concentrated form as dietary supplements, additional research is warranted before we can counsel our patients regarding the safety of such supplements.

Objective: To compare BRCA1 mutations in papillary serous carcinoma of the peritoneum and papillary serous ovarian carcinoma. Methods: Germline DNA from 17 consecutive patients with peritoneal carcinoma was screened for mutations in the BRCA1 gene using single-strand conformation polymorphism analysis. Shifted DNA bands were sequenced. Patients with germline BRCA1 mutations were screened for allelic loss in tumor DNA at the BRCA1 locus. Results: Two of the 17 patients (11%, 95% confidence interval 0.07, 0.37) exhibited the 185 delAG germline BRCA1 mutation described in the Ashkenazi Jewish population. The family history of one patient was notable for a mother and five aunts with breast or ovarian cancer. The other patient had a personal history of breast cancer. Both patients exhibited allelic loss of the normal BRCA1 allele in their tumor. A third patient was found to have a previously undescribed exon 11 single base pair substitution at nucleotide 1239 (CAG to CAC) resulting in a missense mutation (Gln to His). The patient had no family or personal history of breast or ovarian cancer, and her tumor did not exhibit loss of heterozygosity. Conclusion: Germline BRCA1 mutations occur in papillary serous carcinoma of the peritoneum with a frequency comparable to the BRCA1 mutation rate in ovarian cancer. Although the penetrance is unknown, peritoneal carcinoma should be considered a malignancy expressed in the familial breast ovarian cancer syndrome.