Abstract：
Low-grade serous carcinoma (LGSOC) is a rare epithelial ovarian/peritoneal cancer characterized by younger age at diagnosis, relative chemoresistance, prolonged overall survival (OS), and mutations in the mitogen activated protein kinase (MAPK) pathway compared to high-grade serous carcinoma. We describe the genomic profile of LGSOC by next generation sequencing (NGS) and evaluated its potential relationship to clinical outcomes.
The study included 215 women with LGSOC with: 1) pathologically confirmed LGSOC, 2) availability of NGS data, and 3) adequate clinical data. Clinical subgroups were compared for progression-free survival (PFS) and OS. Multivariable Cox regression analysis was performed.
Median age at diagnosis was 46.6 years. The majority had a stage III ovarian primary. One or more mutations were identified in 140 (65.1%) cases; 75 (34.9%) had none. The most common mutations were KRAS (n = 71; 33.0%), NRAS (n = 24; 11.2%), and BRAF (n = 18; 8.4%). Patients with MAPK-mutated tumors (n = 113) (52.6%) had a significantly longer OS compared to those with tumors lacking MAPK pathway mutations (n = 102) (47.4%) [median OS, 147.8 months (95% CI,119.0-176.6) versus 89.5 months (95% CI, 61.4-117.7) (p = 0.01)], respectively. Median OS for patients with MAPK-mutated tumors was also significantly better than for patients whose tumors had no mutations (n = 75) [median OS, 147.8 months (95% CI, 119.0-176.6) versus 78.0 months (95% CI, 57.6-98.3)], respectively (p = 0.001). Median OS for patients with non-MAPK-mutated tumors (n = 27) was 125.1 months (95% CI, 83.9-166.3). In multivariable analysis, having a MAPK mutation was associated with improved OS.
Patients with MAPK-mutated tumors have a significantly improved OS compared to those without MAPK-mutated tumors.
The study included 215 women with LGSOC with: 1) pathologically confirmed LGSOC, 2) availability of NGS data, and 3) adequate clinical data. Clinical subgroups were compared for progression-free survival (PFS) and OS. Multivariable Cox regression analysis was performed.
Median age at diagnosis was 46.6 years. The majority had a stage III ovarian primary. One or more mutations were identified in 140 (65.1%) cases; 75 (34.9%) had none. The most common mutations were KRAS (n = 71; 33.0%), NRAS (n = 24; 11.2%), and BRAF (n = 18; 8.4%). Patients with MAPK-mutated tumors (n = 113) (52.6%) had a significantly longer OS compared to those with tumors lacking MAPK pathway mutations (n = 102) (47.4%) [median OS, 147.8 months (95% CI,119.0-176.6) versus 89.5 months (95% CI, 61.4-117.7) (p = 0.01)], respectively. Median OS for patients with MAPK-mutated tumors was also significantly better than for patients whose tumors had no mutations (n = 75) [median OS, 147.8 months (95% CI, 119.0-176.6) versus 78.0 months (95% CI, 57.6-98.3)], respectively (p = 0.001). Median OS for patients with non-MAPK-mutated tumors (n = 27) was 125.1 months (95% CI, 83.9-166.3). In multivariable analysis, having a MAPK mutation was associated with improved OS.
Patients with MAPK-mutated tumors have a significantly improved OS compared to those without MAPK-mutated tumors.
摘要：
低级别浆液性癌（LGSOC）是一种罕见的上皮性卵巢癌/腹膜癌，其特征是诊断时年龄较小，相对化学抗性，延长总生存期（OS），与高级别浆液性癌相比，丝裂原活化蛋白激酶（MAPK）途径的突变。我们通过下一代测序（NGS）描述了LGSOC的基因组谱，并评估了其与临床结果的潜在关系。
该研究包括215名LGSOC女性，其中：1）经病理证实的LGSOC，2)NGS数据的可用性，3)充分的临床资料。比较临床亚组的无进展生存期（PFS）和OS。进行多变量Cox回归分析。
诊断时的中位年龄为46.6岁。大多数患有III期卵巢原发性。在140例（65.1%）中发现了一个或多个突变；75例（34.9%）没有突变。最常见的突变是KRAS（n=71；33.0%），NRAS（n=24；11.2%），和BRAF（n=18；8.4%）。与缺乏MAPK通路突变的肿瘤患者（n=102）（47.4％）相比，MAPK突变的肿瘤患者（n=113）（52.6％）的OS明显更长[中位OS，147.8个月（95%CI，119.0-176.6）与89.5个月（95%CI，61.4-117.7）（p=0.01）]，分别。MAPK突变肿瘤患者的中位OS也明显优于无突变肿瘤患者（n=75）[中位OS，147.8个月（95%CI，119.0-176.6）与78.0个月（95%CI，57.6-98.3）]，分别(p=0.001)。非MAPK突变肿瘤患者（n=27）的中位OS为125.1个月（95％CI，83.9-166.3）。在多变量分析中，MAPK突变与OS改善相关。
与没有MAPK突变肿瘤的患者相比，MAPK突变肿瘤的患者的OS明显改善。
该研究包括215名LGSOC女性，其中：1）经病理证实的LGSOC，2)NGS数据的可用性，3)充分的临床资料。比较临床亚组的无进展生存期（PFS）和OS。进行多变量Cox回归分析。
诊断时的中位年龄为46.6岁。大多数患有III期卵巢原发性。在140例（65.1%）中发现了一个或多个突变；75例（34.9%）没有突变。最常见的突变是KRAS（n=71；33.0%），NRAS（n=24；11.2%），和BRAF（n=18；8.4%）。与缺乏MAPK通路突变的肿瘤患者（n=102）（47.4％）相比，MAPK突变的肿瘤患者（n=113）（52.6％）的OS明显更长[中位OS，147.8个月（95%CI，119.0-176.6）与89.5个月（95%CI，61.4-117.7）（p=0.01）]，分别。MAPK突变肿瘤患者的中位OS也明显优于无突变肿瘤患者（n=75）[中位OS，147.8个月（95%CI，119.0-176.6）与78.0个月（95%CI，57.6-98.3）]，分别(p=0.001)。非MAPK突变肿瘤患者（n=27）的中位OS为125.1个月（95％CI，83.9-166.3）。在多变量分析中，MAPK突变与OS改善相关。
与没有MAPK突变肿瘤的患者相比，MAPK突变肿瘤的患者的OS明显改善。
