Preventing Ovarian Cancer in High-risk Women: One Surgery at a Time.

Eleven genes have been identified that increase the lifetime risk of developing ovarian cancer. The cumulative cancer risk of ovarian cancer varies with the mutation type and age. Ovarian cancer risk management options include surgical risk reduction with salpingo-oophorectomy and a newer step-wise approach with interval salpingectomy and delayed oophorectomy. Women should be counseled on the pros and cons of hysterectomy in the setting of reducing the risk of other cancers; eliminating the risk of endometrial cancer in Lynch Syndrome, potential risk of serous/serous-like endometrial cancer in BRCA1 carriers, and elimination of progestogen therapy that may increase breast cancer risk.

Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population?

BACKGROUND: Universal tumor testing for defective DNA mismatch repair (MMR) is recommended for all women diagnosed with endometrial cancer to identify those with underlying Lynch syndrome. However, the effectiveness of these screening methods in identifying individuals with Lynch syndrome across the population has not been well studied. The aim of this study was to evaluate outcomes of MMR immunohistochemistry (IHC), mutL homolog 1 (MLH1) methylation, and microsatellite instability (MSI) analysis among patients with endometrial cancer. METHODS: A complete systematic search of online databases (PubMed, EMBASE, MEDLINE, and the Cochrane Library) for 1990-2018 was performed. A DerSimonian-Laird random effects model meta-analysis was used to estimate the weighted prevalence of Lynch syndrome diagnoses. RESULTS: The comprehensive search produced 4400 publications. Twenty-nine peer-reviewed studies met the inclusion criteria. Patients with endometrial cancer (n = 6649) were identified, and 206 (3%) were confirmed to have Lynch syndrome through germline genetic testing after positive universal tumor molecular screening. Among 5917 patients who underwent tumor IHC, 28% had abnormal staining. Among 3140 patients who underwent MSI analysis, 31% had MSI. Among patients with endometrial cancer, the weighted prevalence of Lynch syndrome germline mutations was 15% (95% confidence interval [CI], 11%-18%) with deficient IHC staining and 19% (95% CI, 13%-26%) with a positive MSI analysis. Among 1159 patients who exhibited a loss of MLH1 staining, 143 (13.7%) were found to be MLH1 methylation-negative among those who underwent methylation testing, and 32 demonstrated a germline MLH1 mutation (2.8% of all absent MLH1 staining cases and 22.4% of all MLH1 methylation-negative cases). Forty-three percent of patients with endometrial cancer who were diagnosed with Lynch syndrome via tumor typing would have been missed by family history-based screening alone. CONCLUSIONS: Despite the widespread implementation of universal tumor testing in endometrial cancer, data regarding testing results remain limited. This study provides predictive values that will help practitioners to evaluate abnormal results in the context of Lynch syndrome and aid them in patient counseling.

Metachronous Uterine Endometrioid Adenocarcinoma and Peritoneal Mesothelioma in Lynch Syndrome: A Case Report.

Lynch syndrome is a hereditary disease with germline mutation in a DNA mismatch repair gene, most often presenting with colorectal and/or endometrial carcinomas; however, the spectrum of Lynch syndrome-associated tumors is expanding. In this article, we report a case of a primary peritoneal epithelioid mesothelioma that developed in a Lynch syndrome patient 10 months after diagnosis of uterine endometrioid adenocarcinoma. To our knowledge, this is the first reported case of a Lynch syndrome patient with metachronous uterine endometrioid adenocarcinoma and primary peritoneal mesothelioma.

The impact of risk-reducing gynaecological surgery in premenopausal women at high risk of endometrial and ovarian cancer due to Lynch syndrome.

Women with Lynch syndrome (LS) have a significantly increased lifetime risk of endometrial cancer (40-60 %) and ovarian cancer (7-12 %). Currently there is little evidence to support the efficacy of screening for the early detection of these cancers. Another option is risk-reducing hysterectomy and/or bilateral salpingo-oophorectomy (BSO). Research on the impact of BSO in premenopausal women with a non-LS associated family history cancer has generally shown that women have a high level of satisfaction about their decision to undergo surgery. However, debilitating menopausal symptoms and sexual dysfunction are common post-surgical problems. We used a mixed methods study to explore the impact of risk-reducing gynaecological surgery in women with LS: 24 women were invited to take part; 15 (62.5 %) completed validated questionnaires and 12 (50 %) participated in semi-structured interviews. Our results suggest that risk reducing surgery does not lead to significant psychological distress and the women tend not to think or worry much about developing cancer. However, they tend to be distressed about the physical and somatic symptoms associated with menopause; their social well-being is somewhat affected, but sexual difficulties are minimal. The women reported being overwhelmingly satisfied with their decision to have surgery and with the quality of information they received prior to the operation. However, they felt underprepared for menopausal symptoms and received conflicting advice about whether or not to use HRT. Recommendations from the study include that professionals discuss the menopause, its side effects and HRT in detail prior to surgery.

Ovarian cancer: etiology, risk factors, and epidemiology.

Little is known regarding the early aspects of ovarian carcinogenesis. As a consequence, the identification of women at risk for the disease is based primarily on clinical grounds, with family history being the most important risk factor. In this review, we will discuss the various hypotheses regarding ovarian etiology and pathogenesis. In addition, we will discuss the epidemiology of ovarian cancer, including hereditary, reproductive, hormonal, inflammatory, dietary, surgical, and geographic factors that influence ovarian cancer risk.

Genética del cáncer colorrectal y poliposis / Genetics of colorectal cancer and polyposis

En la última década se ha producido un avance muy significativo en el campo del cáncer colorrectal hereditario. Estos avances se han producido principalmente en la identificación del síndrome de Lynch o cáncer colorrectal hereditario no polipósico, mediante criterios clínicos y técnicas moleculares (inmunohistoquímica, inestabilidad de microsatélites), así como en la reciente implicación del gen MYH en la carcinogénesis colorectal. Las mutaciones bialélicas en el gen MYH causan, por un lado, una forma de poliposis adenomatosa familiar atenuada con herencia recesiva, y por otro lado, predisponen al desarrollo de cáncer colorrectal. Es fundamental conocer los síndromes hereditarios asociados al cáncer colorrectal para así poder detectar los individuos potencialmente portadores de mutaciones, y ser derivados a centros de referencia especializados para la realización de estudios moleculares y la aplicación de programas de cribado y vigilancia específicos (AU)

In the last decade, highly significant advances have been made in the field of hereditary colorectal cancer. These advances have been produced mainly in the identification of Lynch syndrome or hereditary non-polyposic colorectal cancer through clinical criteria and molecular techniques (immunohistochemistry, microsatellite instability), as well as in the recent implication of the MYH gene in colorectal carcinogenesis. Biallelic mutations in the MYH gene cause a form of attenuated familial adenomatous polyposis, with recessive inheritance, on the one hand, and predispose affected individuals to the development of colorectal cancer, on the other hand. It is essential to determine the hereditary syndromes associated with colorectal cancer in order to detect individuals potentially carrying mutations and to refer these individuals to specialized centers performing molecular studies and specific screening and monitoring programs (AU)