KRAS mutation in primary ovarian serous borderline tumors correlates with tumor recurrence

• Published in: Virchows Archiv : an international journal of pathology Vol. 483; no. 1; pp. 71 - 79
• Main Authors: McHenry, Austin, Rottmann, Douglas A., Buza, Natalia, Hui, Pei
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2023; Springer Nature B.V
• Subjects: Biomarkers; Cystadenocarcinoma, Serous - genetics; Cystadenocarcinoma, Serous - pathology; Cystadenoma, Serous - genetics; Cystadenoma, Serous - pathology; Female; Humans; Implants; K-Ras protein; Kinases; MAP kinase; Medicine; Medicine & Public Health; Mutation; Neoplasm Recurrence, Local - genetics; Original Article; Ovarian Neoplasms - pathology; Ovaries; Pathology; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Rank tests; Survival; Transplants & implants; Tumors; Ovarian serous borderline tumor; mutation; Disease-free survival; KRAS mutation
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-023-03564-z

Oncogenic activation of the mitogen-activated protein kinase (MAPK) pathway due to KRAS or BRAF gain-of-function mutation is frequently found in ovarian serous borderline tumor (SBT) and their extraovarian implants. We investigated mutational status of KRAS and BRAF of the primary ovarian SBTs that had a high stage presentation in correlation with clinical outcome. Among 39 consecutive primary SBTs with either invasive implants (20 cases) or non-invasive implants (19 cases), KRAS and BRAF mutational analysis was informative in 34 cases. Sixteen cases (47%) harbored a KRAS mutation, while 5 cases (15%) had a BRAF V600E mutation. High-stage disease (IIIC) was seen in 31% (5/16) of patients with a KRAS mutation and 39% (7/18) of patients without a KRAS mutation ( p  = 0.64). KRAS mutations were present in 9/16 (56%) tumors with invasive implants/LGSC versus 7/18 (39%) tumors with non-invasive implants ( p  = 0.31). BRAF mutation was seen in 5 cases with non-invasive implants. Tumor recurrence was seen in 31% (5/16) of patients with a KRAS mutation, compared to 6% (1/18) of patients without a KRAS mutation ( p  = 0.04). A KRAS mutation predicted an adverse disease-free survival (31% survival at 160 months) compared to those with wild-type KRAS (94% at 160 months; log-rank test, p  = 0.037; HR 4.47). In conclusion, KRAS mutation in primary ovarian SBTs is significantly associated with a worse disease-free survival, independent of the high tumor stage or histological subtypes of extraovarian implant. KRAS mutation testing of primary ovarian SBT may servce as a useful biomarker for tumor recurrence.