OBJECTIVES: The goals of this study were to perform a comprehensive assessment of the prevalence of KRAS oncogene mutations in invasive epithelial ovarian carcinomas of various histologic subtypes, and for any subgroup(s) in which KRAS mutation was found to be common, to address the hypothesis that those tumors without KRAS mutation had sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene. METHODS: A total of 104 primary, invasive epithelial ovarian carcinomas from a 10-year period at this institution were selected for study based on histologic classification. The histologic cell type was serous in 21 cases, endometrioid in 30 cases, clear cell in 31 cases, and mucinous in 22 cases. Additional clinical and pathological information was abstracted from patient records, and pathology review was performed for all cases. Direct sequence analysis of exon 2 of the KRAS gene, containing codon 12, was performed using DNA isolated from all tumor specimens. Sequence analyses of exons 11 and 15 of the BRAF gene were performed for the 22 cases of mucinous ovarian carcinoma. RESULTS: Activating KRAS mutations were more common in mucinous tumors (50%) than in all other histologic types combined (5%; P < 10(-7)). Mutation of KRAS was more common in stage I tumors than in advanced stage tumors (P = 0.0004). Of the 11 mucinous tumors with KRAS mutations, 6 were of Mullerian (endocervical) type and 5 were of gastrointestinal type. No mucinous tumor was found to harbor a BRAF mutation. CONCLUSIONS: These data indicate that KRAS oncogene mutations exist in several histologic types of invasive epithelial ovarian carcinoma, especially stage I tumors, but are common only in tumors of mucinous histology. Mutations are equally prevalent in mucinous ovarian cancers of Müllerian and gastrointestinal types. In contrast to other solid tumor types frequently affected by KRAS mutation, mucinous ovarian cancers without a KRAS mutation have not sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene.
OBJECTIVES: The goals of this study were to perform a comprehensive assessment of the prevalence of KRAS oncogene mutations in invasive epithelial ovarian carcinomas of various histologic subtypes, and for any subgroup(s) in which KRAS mutation was found to be common, to address the hypothesis that those tumors without KRAS mutation had sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene. METHODS: A total of 104 primary, invasive epithelial ovarian carcinomas from a 10-year period at this institution were selected for study based on histologic classification. The histologic cell type was serous in 21 cases, endometrioid in 30 cases, clear cell in 31 cases, and mucinous in 22 cases. Additional clinical and pathological information was abstracted from patient records, and pathology review was performed for all cases. Direct sequence analysis of exon 2 of the KRAS gene, containing codon 12, was performed using DNA isolated from all tumor specimens. Sequence analyses of exons 11 and 15 of the BRAF gene were performed for the 22 cases of mucinous ovarian carcinoma. RESULTS: Activating KRAS mutations were more common in mucinous tumors (50%) than in all other histologic types combined (5%; P < 10(-7)). Mutation of KRAS was more common in stage I tumors than in advanced stage tumors (P = 0.0004). Of the 11 mucinous tumors with KRAS mutations, 6 were of Mullerian (endocervical) type and 5 were of gastrointestinal type. No mucinous tumor was found to harbor a BRAF mutation. CONCLUSIONS: These data indicate that KRAS oncogene mutations exist in several histologic types of invasive epithelial ovarian carcinoma, especially stage I tumors, but are common only in tumors of mucinous histology. Mutations are equally prevalent in mucinous ovarian cancers of Müllerian and gastrointestinal types. In contrast to other solid tumor types frequently affected by KRAS mutation, mucinous ovarian cancers without a KRAS mutation have not sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene.
Authors: Katherine C Kurnit; Abdulrahman K Sinno; Bryan M Fellman; Aaron Varghese; Rebecca Stone; Anil K Sood; David M Gershenson; Kathleen M Schmeler; Anais Malpica; Amanda N Fader; Michael Frumovitz Journal: Obstet Gynecol Date: 2019-12 Impact factor: 7.661
Authors: Michael Frumovitz; Kathleen M Schmeler; Anais Malpica; Anil K Sood; David M Gershenson Journal: Gynecol Oncol Date: 2010-03-23 Impact factor: 5.482
Authors: Daniela Matei; Michael W Sill; Heather A Lankes; Koen DeGeest; Robert E Bristow; David Mutch; S Diane Yamada; David Cohn; Valerie Calvert; John Farley; Emanuel F Petricoin; Michael J Birrer Journal: J Clin Oncol Date: 2010-11-22 Impact factor: 44.544
Authors: L Quaye; H Song; S J Ramus; A Gentry-Maharaj; E Høgdall; R A DiCioccio; V McGuire; A H Wu; D J Van Den Berg; M C Pike; E Wozniak; J A Doherty; M A Rossing; R B Ness; K B Moysich; C Høgdall; J Blaakaer; D F Easton; B A J Ponder; I J Jacobs; U Menon; A S Whittemore; S Krüger-Kjaer; C L Pearce; P D P Pharoah; S A Gayther Journal: Br J Cancer Date: 2009-02-24 Impact factor: 7.640