Hereditary cancer syndromes are defined as syndromes, where the genetics of cancer are the result of low penetrant polymorphisms or of a single gene disorder inherited in a mendelian fashion. During ...the last decade, compelling evidence has accumulated that approximately 5-10% of all cancers could be attributed to hereditary cancer syndromes. A tremendous progress has been made over the last decade in the evaluation and management of these syndromes. However, hereditary syndromes associated with gynecologic malignancies still present significant challenge for oncogynecologists. Oncogynecologists tend to pay more attention to staging, histological type and treatment options of gynecological cancers than thinking of inherited cancers and taking a detailed family history. Moreover, physicians should also be familiar with screening strategies in patients with inherited gynecological cancers. Lynch syndrome and hereditary breast-ovarian cancer syndrome are the most common and widely discussed syndromes in medical literature. The aim of the present review article is to delineate and emphasize the majority of hereditary gynecological cancer syndromes, even these, which are rarely reported in oncogynecology. The following inherited cancers are briefly discussed: Lynch syndrome; "site-specific" ovarian cancer and hereditary breast-ovarian cancer syndrome; Cowden syndrome; Li-Fraumeni syndrome; Peutz-Jeghers syndrome; ataxia-telangiectasia; DICER1- syndrome; gonadal dysgenesis; tuberous sclerosis; multiple endocrine neoplasia type I, II; hereditary small cell carcinoma of the ovary, hypercalcemic type and hereditary undifferentiated uterine sarcoma; hereditary diffuse gastric cancer and MUTYH-associated polyposis. Epidemiology, pathogenesis, diagnosis, pathology and screening of these syndromes are discussed. General treatment recommendations are beyond the scope of this review.
Aims
Prophylactic total hysterectomy (TH) and bilateral salpingo‐oophorectomy (BSO) have become routine procedures in women at genetic risk for gynaecological malignancies. Intra‐operative pathology ...diagnosis of an occult malignancy provides the opportunity for immediate surgical staging and helps to avoid a second surgery. However, no standard guidelines exist for optimal intra‐operative evaluation (IOE) of these specimens. We performed a retrospective analysis of prophylactic TH and BSO cases to assess the presence of gross findings, frozen and permanent section sampling practices, frozen section diagnoses and diagnostic discrepancies.
Methods and results
All prophylactic TH and BSO cases between 1990 and 2017 were retrieved from our departmental archives. A total of 413 cases were included in the study: 27 with Lynch syndrome (LS), 222 with germline BRCA 1 or 2 mutations and 164 cases with strong family or personal history (non‐Lynch/non‐BRCA). Only fewer than half of all cases (159 of 413; 38.5%) were sent for IOE, 15 of 27 (56%) LS cases, 93 of 222 (42%) BRCA cases and 51 of 164 (31%) non‐Lynch/non‐BRCA cases. A total of 19 patients (4.6% of patients combining all three groups) had a final diagnosis of malignancy or premalignancy on permanent sections. Of these 19 cases, eight had a corresponding gross lesion (42%) and could have been diagnosed on frozen section; however, only one of them underwent IOE.
Conclusions
Our results highlight the potential benefits and challenges of IOE in this setting and may provide a basis for future practice recommendations.
Hereditary breast ovarian cancer (HBOC) syndrome is an autosomal dominant disease linked to mutations in the BRCA1 and BRCA2 genes in 90 percent of affected families. Female mutation carriers are ...highly susceptible to aggressive, often disseminated, usually fatal pelvic-abdominal carcinomatosis. This cancer risk can be markedly reduced by surgical removal of the internal gynecologic organs before the end of the fourth decade of life and by using estrogen–progestin formulations marketed for many years as combined oral contraceptives (COCs). Both risk-reducing methods are associated with unfavorable effects. Relying on the principle of double effect, this essay argues for the ethical justification of prophylactic surgery and the use of COC to reduce the risk of gynecologic cancer in HBOC syndrome mutation carriers.
Summary: Hereditary breast ovarian cancer syndrome is an autosomal dominant disease linked to mutations in the BRCA1 and BRCA2 genes in most affected families. Female mutation carriers are highly susceptible to aggressive, often disseminated, usually fatal pelvic-abdominal carcinomatosis. This cancer risk can be markedly reduced by surgical removal of the internal gynecologic organs before the end of the fourth decade of life and by using estrogen-progestin formulations marketed for many years as combined oral contraceptives. Both risk-reducing methods are associated with unfavorable effects. Relying on the principle of double effect, this essay argues for the ethical justification for those unfavorable effects.
Endometrial cancer is the most common gynecologic cancer in developed countries and is rising in incidence globally. Although the 5-year survival rates are >80%, factors beyond conventional ...pathologic features that predict clinical outcomes are still being elucidated. The aims of this study were to define the prevalence and associations of deficient mismatch repair (dMMR) protein expression (MLH1, MSH2, MSH6, PMS2) by immunohistochemistry in a multiethnic Southeast Asian cohort with endometrioid endometrial cancer. A total of 77 patients with adequate formalin-fixed paraffin-embedded specimens were identified. The sections were stained in 2 centers for 4 MMR proteins and examined by 2 independent specialist histopathologists. The mean age for the cohort was 58.6 yr, with 19.4% (15/77) of patients' cancers showing loss of 2 MMR proteins. All 13 cancers with absent MLH1 showed PMS2 loss (13/15), whereas absent MSH2 correlated with MHS6 loss (2/15). There were no significant differences for dMMR cases in age, body mass index, histopathologic characteristics, and clinical outcomes. In dMMR cases, an overrepresentation of patients of Indian ethnic origin was observed compared with Chinese and Malays. These findings suggest that dMMR protein expression in a Southeast Asian endometrial cancer cohort does not correlate with disease outcomes.
Herencia y genética del cáncer ginecológico Manrique Fuentes, M.G; Salamanca Ballesteros, A; Gallo Vallejo, J.L
Clínica e investigación en ginecología y obstetricia,
July-August 2013, Volume:
40, Issue:
4
Journal Article
Peer reviewed
Resumen La mayoría de los cánceres ginecológicos son esporádicos, no hereditarios. Pese a ello, debemos tener en cuenta el papel de la herencia, sobre todo en el cáncer de mama y ovario, ya que ...aunque solo el 10% se van a relacionar con una mutación hereditaria, actualmente se dispone de la posibilidad de realizar estudio genético. Por motivos éticos y efectivos, dicho estudio no está indicado en toda la población, sino que se ha de reservar para aquellas pacientes con un mayor riesgo de cáncer hereditario, en base a antecedentes familiares y personales. Sin embargo, aún no se han establecido unos criterios claros para el estudio genético, seguimiento y medidas preventivas a adoptar en dichas pacientes. La presente revisión tiene como finalidad aclarar cuáles son los criterios a partir de los cuales podemos identificar a aquellas pacientes con un mayor riesgo de presentar cáncer hereditario, y con ello poder ofrecerles información sobre la posibilidad de estudio genético, así como de las diferentes opciones de seguimiento y medidas profilácticas disponibles.
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