SeminarOvarian cancer
Section snippets
Epidemiology and risk factors
Epithelial ovarian cancer results from malignant transformation of the ovarian surface epithelium, which is contiguous with the peritoneal epithelium.1 The disease is the sixth most common cancer in women.2 Most patients present with advanced disease (figure 1) and have a poor prognosis with present therapies. Advances in chemotherapy and improved understanding of genetic risk factors and molecular pathogenesis have provided new treatment possibilities. We describe the clinical and molecular
Pathology
Epithelial ovarian cancers are classified by histopathological grade (1–3) and appearance into serous (most common), mucinous, endometrioid, and, less commonly, clear cell, transitional, squamous, mixed, and undifferentiated subtypes. Additionally, fallopian tube and primary peritoneal cancers occur that morphologically and clinically resemble epithelial ovarian cancers, possibly because the same embryonic precursor is shared by the ovarian surface epithelium and the peritoneal and fallopian
Causes and pathogenesis
Although the subtypes of epithelial ovarian cancer possess unique molecular aberrations (table 1) and transcriptional signatures, their morphological features resemble the specialised epithelia of the reproductive tract that derive from the Müllerian ducts. Research suggests that they might all arise from one surface epithelium precursor cell with specific path of differentiation regulated by embryonic pathways involving HOX genes (figure 3).16, 17, 18 HOX genes are not usually expressed in
Screening
Early detection might substantially improve survival if metastatic disease results from progression of clinically detectable early lesions, and if cancers remain localised for a sufficient interval to allow cost-effective screening.28 In view of the prevalence of epithelial ovarian cancer, strategies for early detection should have high sensitivity (>75%) and very high specificity (99·6%) to attain a positive predictive value of 10% or greater. Serum CA125 concentration does not have the
Staging and diagnosis
Panel 1 shows staging of epithelial ovarian cancers.36 From the primary tumour, propagation can occur throughout the abdominopelvic peritoneal compartment (figure 1) and to retroperitoneal pelvic, periaortic, suprarenal, mesenteric, and mesocolic lymph nodes. The most common extra-abdominal site of disease is the pleural space. Less frequently, distant metastases occur in the parenchyma of the liver, lungs, and other organs. The rates of long-term survival (>10 years) in patients with
Initial surgical therapy
Table 3 summarises treatment strategies. If epithelial ovarian cancer is suspected on the basis of physical examination and imaging, an exploratory laparotomy is usually done for histological confirmation, staging, and tumour debulking.1 The standard comprehensive surgical staging approach consists of a total abdominal hysterectomy and BSO along with examination of all peritoneal surfaces, an infracolic omentectomy, biopsies of pelvic and para-aortic lymph nodes and clinically uninvolved areas,
Novel therapeutics and targets
Novel inhibitors such as epidermal growth factor receptor (EGFR) family inhibitors (eg, cetuximab, erlotinib, trastuzumab) or inhibitors of Kit have not had a major effect on the treatment of epithelial ovarian cancer, probably because EGFR, HER2, and KIT aberrations, which are associated with responsiveness to these therapies in other tumour types, are uncommon in this disease.122, 123 Attempts to replace TP53 have also been unsuccessful.124 However, advances in our understanding of
Conclusion
A plateau has been reached regarding the benefits associated with intravenous administration of cytotoxic chemotherapy in epithelial ovarian cancer. However, advances in screening, novel targeted therapies, and widespread use of practical intraperitoneal drug delivery techniques will probably improve patient outcomes. Although the list of genomic aberrations in this disease is daunting, a systems approach and the integration of therapies targeting multiple component genes of important genetic
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