High-Grade Serous Ovarian Cancer: Basic Sciences, Clinical and Therapeutic Standpoints

Abstract

Among a litany of malignancies affecting the female reproductive tract, that of the ovary is the most frequently fatal. Moreover, while the steady pace of scientific discovery has fuelled recent ameliorations in the outcomes of many other cancers, the rates of mortality for ovarian cancer have been stagnant since around 1980. Yet despite the grim outlook, progress is being made towards better understanding the fundamental biology of this disease and how its biology in turn influences clinical behaviour. It has long been evident that ovarian cancer is not a unitary disease but rather a multiplicity of distinct malignancies that share a common anatomical site upon presentation. Of these, the high-grade serous subtype predominates in the clinical setting and is responsible for a disproportionate share of the fatalities from all forms of ovarian cancer. This review aims to provide a detailed overview of the clinical-pathological features of ovarian cancer with a particular focus on the high-grade serous subtype. Along with a description of the relevant clinical aspects of this disease, including novel trends in treatment strategies, this text will inform the reader of recent updates to the scientific literature regarding the origin, aetiology and molecular-genetic basis of high-grade serous ovarian cancer (HGSOC).

Keywords: BRCA; chemotherapy; cortical inclusion cysts; debulking surgery; genetically-engineered mouse models; high-grade serous ovarian cancer; homologous recombination; mutant p53; ovarian surface epithelium; serous tubular intra-epithelial carcinoma.

Figure 1

Heterogeneity of the histopathological architecture of high-grade serous cancer. (A): solid architecture (original magnification × 20); (B): glandular architecture with slit-like spaces (original magnification × 10; (C): papillary architecture (original magnification × 5); (D): cribriform and pseudoendometroid architecture (original magnification × 20); (E): solid architecture with “geographic” necrosis (original magnification × 10); (F): solid architecture with tumour infiltrating lymphocytes (original magnification × 20).

Figure 2

Cytological features of high-grade serous cancer. (A): Multinucleated tumor giant cells; (B): severe pleomorphism and prominent nucleoli; (C): frequent mitotic figures; (D): psammoma bodies. All original magnifications × 40.

Figure 3

Immunological markers typically seen in high-grade serous ovarian cancer. (A): p53; (B): WT-1; (C): p16; (D): CK7; (E): CK20; (F): PAX8; (G): ER; (H): PR. All original magnifications × 10.

Figure 4

Histopathological features (A), risk factors (B) and symptoms (C) of high-serous ovarian cancer.

Figure 5

Historical perspectives of the treatment of high-grade serous ovarian cancer. (A) Evolution of chemotherapies; (B) salvage therapies for recurrent disease.