[Molecular pathology of epithelial ovarian neoplasias: from the phenotype-genotype correlation to new targets in diagnostics and therapy].
Despite the fact that ovarian carcinomas are phenotypically heterogeneous, they can be divided into two main groups with common pathogenetic mechanisms. Based on clinical, pathological and molecular parameters, a relatively large group of tumors can be distinguished with stepwise development from benign precursors and borderline tumors to invasive carcinomas (type I). Depending on the morphological phenotype, characteristic genetic changes can be observed, such as mutations in KRAS and BRAF in serous borderline tumors and low-grade serous carcinomas. Mutations in KRAS are also frequently detected in mucinous borderline tumors and mucinous carcinomas. The group of endometrioid tumors is characterized by mutations in components of the Wnt-signal transduction pathway and PTEN or microsatellite instability. The second large group of tumors (type II) includes tumors with "de novo" development of highly malignant carcinomas such as the conventional (moderately to poorly differentiated) high-grade serous carcinomas, undifferentiated carcinomas and malignant mixed mesodermal tumors. These tumors are associated with frequent mutations in p53 and complex chromosomal alterations. In the future, the combined analysis of morphological parameters, genetic changes, gene-expression profiling and protein data will reveal possible diagnostic and therapeutic targets for ovarian carcinomas.
Staebler
A
A
Institut für Pathologie, Westfälische Wilhelms-Universität, Domagkstrasse 17, 48149 Münster, Germany. Annette.Staebler@ukmuenster.de
Diebold
J
J
D005260:Female; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D010051:Ovarian Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins