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New insights on the pathogenesis of ovarian carcinoma: molecular basis and clinical implications.
- Source :
-
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology [Gynecol Endocrinol] 2012 Aug; Vol. 28 (8), pp. 582-6. Date of Electronic Publication: 2012 Feb 04. - Publication Year :
- 2012
-
Abstract
- Ovarian carcinoma can be subdivided into two categories termed type I and type II. Type I tumours, usually having an indolent clinical behaviour, are often detected in early stage, and rarely harbour p53 gene mutations. Each histological type has a distinct molecular profile with mutations of genes involved in different signalling transduction pathways, such as KRAS, BRAF, CTNNB1, PTEN, PIK3CA and ARID1A. Type II tumours, accounting for 75% of the cases, have a very aggressive biological behaviour, are usually in advanced stage at presentation, harbour p53 gene mutations in 80% of the cases, and sometimes have alterations of homologous recombination (HR). Both type I and type II tumours arise from extra-ovarian precursors. Serous carcinomas derive from tubal epithelium, endometrioid and clear cell carcinomas from endometrial tissue, and mucinous and Brenner tumours from transitional epithelial cells located near the tubo-peritoneal junction. These new concepts on the pathogenesis of ovarian carcinoma could deeply modify both the preventive approach in women with germ-line BRCA₁ or BRCA₂ mutations and the treatment of patients with advanced or recurrent disease. For instance, BRAF inhibitors could be used in low-grade serous carcinomas, PIK3CA inhibitors could be employed in clear cell carcinoma, and poly (ADP-ribose) polymerase inhibitors could be used not only in hereditary ovarian carcinoma but also in non-hereditary, high-grade serous ovarian carcinoma which sometimes shows defective HR.
- Subjects :
- Animals
Carcinoma genetics
Carcinoma metabolism
Endometrial Neoplasms genetics
Endometrial Neoplasms metabolism
Endometrial Neoplasms pathology
Fallopian Tube Neoplasms genetics
Fallopian Tube Neoplasms metabolism
Fallopian Tube Neoplasms pathology
Female
Humans
Hyperplasia
Mutation
Neoplasm Proteins genetics
Neoplasm Proteins metabolism
Ovarian Neoplasms genetics
Ovarian Neoplasms metabolism
Signal Transduction drug effects
Antineoplastic Agents therapeutic use
Carcinoma drug therapy
Carcinoma secondary
Molecular Targeted Therapy
Neoplasm Proteins antagonists & inhibitors
Ovarian Neoplasms drug therapy
Ovarian Neoplasms secondary
Subjects
Details
- Language :
- English
- ISSN :
- 1473-0766
- Volume :
- 28
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 22304686
- Full Text :
- https://doi.org/10.3109/09513590.2011.649595