Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 300 E 66 Street, New York, NY 10065, USA.
Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 408 E 69 Street, New York, NY, 10065, USA.
Cancer. 2013 Feb 1;119(3):548-554. doi: 10.1002/cncr.27782. Epub 2012 Aug 28.
Low-grade serous (LGS) ovarian cancer is a chemoresistant disease that accounts for 10% of serous ovarian cancers. Prior studies have reported that 28% to 35% of serous borderline (SB)/LGS ovarian tumors harbor a BRAF mutation, suggesting that BRAF inhibitors may be a rational therapeutic approach for this disease. In the current study, the authors sought to determine whether BRAF or KRAS mutation status was associated with disease stage and/or histology in patients with SB and LGS ovarian cancer.
Genetic profiles were constructed for 75 SB and LGS ovarian tumors to determine BRAF and KRAS mutation status. The incidence and identity of BRAF and KRAS mutations were defined, and the results were correlated with disease stage, response to treatment, and overall survival.
Of 75 samples examined, 56 tumors (75%) had SB histology, and 19 tumors (25%) had LGS histology. Fifty-seven percent of tumors harbored either a KRAS mutation (n = 17) or a BRAF mutation (a valine-to-glutamate substitution at residue 600 [V600E]; n = 26). The BRAF V600E mutation was associated significantly with early disease stage (stage I/II; P < .001) and SB histology (P = .002). KRAS mutations were not associated significantly with disease stage or histology. Of the 22 patients (29%) who required chemotherapy, 20 had tumors with wild-type KRAS/BRAF, 2 had KRAS mutant tumors, and none had tumors that harbored a BRAF mutation. All patients with BRAF tumors remained alive at a median follow-up of 3.6 years (range, 1.9-129.3 months).
V600E BRAF mutations were present in 35% of patients who had SB/LGS ovarian cancers. The presence of the BRAF V600E mutation in SB/LGS ovarian cancer was associated with early stage disease and improved prognosis. The authors concluded that patients with SB/LGS ovarian cancer who require systemic therapy are unlikely to have BRAF mutant tumors.
低级别浆液性（LGS）卵巢癌是一种化疗耐药疾病，占浆液性卵巢癌的 10%。先前的研究报告称，28%至 35%的浆液性交界性（SB）/LGS 卵巢肿瘤存在 BRAF 突变，这表明 BRAF 抑制剂可能是治疗这种疾病的合理方法。在本研究中，作者试图确定 BRAF 或 KRAS 突变状态是否与 SB 和 LGS 卵巢癌患者的疾病分期和/或组织学相关。
构建了 75 例 SB 和 LGS 卵巢肿瘤的遗传图谱，以确定 BRAF 和 KRAS 突变状态。定义了 BRAF 和 KRAS 突变的发生率和特征，并将结果与疾病分期、治疗反应和总生存相关联。
在 75 例检查的样本中，56 例肿瘤（75%）具有 SB 组织学，19 例肿瘤（25%）具有 LGS 组织学。57%的肿瘤存在 KRAS 突变（n = 17）或 BRAF 突变（第 600 位缬氨酸到谷氨酸取代[V600E]；n = 26）。BRAF V600E 突变与早期疾病分期（I/II 期；P<.001）和 SB 组织学显著相关（P=.002）。KRAS 突变与疾病分期或组织学无显著相关性。在需要化疗的 22 名患者（29%）中，20 名患者的肿瘤具有野生型 KRAS/BRAF，2 名患者的肿瘤具有 KRAS 突变，没有患者的肿瘤存在 BRAF 突变。所有具有 BRAF 肿瘤的患者在中位随访 3.6 年后仍存活（范围为 1.9-129.3 个月）。
SB/LGS 卵巢癌患者中有 35%存在 V600E BRAF 突变。SB/LGS 卵巢癌中 BRAF V600E 突变的存在与早期疾病和改善的预后相关。作者得出结论，需要全身治疗的 SB/LGS 卵巢癌患者不太可能存在 BRAF 突变肿瘤。
