title: Low Grade Serous Ovarian Carcinoma: from the molecular characterization to the best therapeutic strategy.
abstract: Low Grade Serous Ovarian Carcinoma, LGSOC, is certainly a rare disease, accounting for only a small proportion of all ovarian carcinomas, nevertheless in the last decade we have acquired many data about its molecular and clinical features and it has been largely accepted that it has distinct pathogenesis, genetic aberrations and clinical behavior compared to High Grade Serous Ovarian Carcinoma, HGSOC, which is the most common ovarian cancer histotype. A large number of series pointed out the high rate of KRAS and BRAF mutations in LGSOCs and Serous Borderline Tumors, SBLTs, in contrast with their rarity in HGSOC. Such finding, together with the recurrent observation of focus of LGSOC associated with areas of SBLT in the same lesion, led to abandon the traditional histology classification, defining three types of serous carcinomas, in favor of a new dualistic grading system which recognizes only LG and HG carcinomas corresponding to distinct tumorigenesis pathways, the former based on KRAS/BRAF mutations and alteration of the MAP/ERK signaling, the latter characterized by early genetic instability and wild type status of KRAS and BRAF. LGSOC shows favorable overall survival, compared to general ovarian cancer population, but worrying resistance to conventional treatments. MEK inhibitors are emerging as active agents and may well represent an effective therapeutic strategy in the near future.
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro Del Portillo, 200, 00128 Rome, Italy. Electronic address: chiaradellapepa@hotmail.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Della Pepa
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro Del Portillo, 200, 00128 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro Del Portillo, 200, 00128 Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.affiliation: Surgical Pathology Unit, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola, 52, 80131 Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Losito
authors.affiliation: Department of Urology and Gynecology, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola, 52, 80131 Naples, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Pisano
authors.affiliation: Department of Urology and Gynecology, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola, 52, 80131 Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Di Napoli
authors.affiliation: Department of Urology and Gynecology, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola, 52, 80131 Naples, Italy.
authors.forename: Sabrina Chiara
authors.initials: SC
authors.lastname: Cecere
authors.affiliation: Department of Clinical Medicine and Surgery, School of Medicine, University of Naples "Federico II", 80131 Napoli, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: Gargiulo
authors.affiliation: Department of Urology and Gynecology, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Via Mariano Semmola, 52, 80131 Naples, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; 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*
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020929:Mitogen-Activated Protein Kinase Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: BRAF; Chemoresistance; KRAS; Low-Grade Serous; MEK-inhibitors; Ovarian cancer