Anglesio Michael S, Arnold Jeremy M, George Joshy, Tinker Anna V, Tothill Richard, Waddell Nic, Simms Lisa, Locandro Bianca, Fereday Sian, Traficante Nadia, Russell Peter, Sharma Raghwa, Birrer Michael J, deFazio Anna, Chenevix-Trench Georgia, Bowtell David D L
Peter MacCallum Cancer Centre, Victoria, Australia.
Mol Cancer Res. 2008 Nov;6(11):1678-90. doi: 10.1158/1541-7786.MCR-08-0193.
Approximately, 10% to 15% of serous ovarian tumors fall into the category designated as tumors of low malignant potential (LMP). Like their invasive counterparts, LMP tumors may be associated with extraovarian disease, for example, in the peritoneal cavity and regional lymph nodes. However, unlike typical invasive carcinomas, patients generally have a favorable prognosis. The mutational profile also differs markedly from that seen in most serous carcinomas. Typically, LMP tumors are associated with KRAS and BRAF mutations. Interrogation of expression profiles in serous LMP tumors suggested overall redundancy of RAS-MAPK pathway mutations and a distinct mechanism of oncogenesis compared with high-grade ovarian carcinomas. Our findings indicate that activating mutation of the RAS-MAPK pathway in serous LMP may be present in >70% of cases compared with approximately 12.5% in serous ovarian carcinomas. In addition to mutations of KRAS (18%) and BRAF (48%) mutations, ERBB2 mutations (6%), but not EGFR, are prevalent among serous LMP tumors. Based on the expression profile signature observed throughout our serous LMP cohort, we propose that RAS-MAPK pathway activation is a requirement of serous LMP tumor development and that other activators of this pathway are yet to be defined. Importantly, as few nonsurgical options exist for treatment of recurrent LMP tumors, therapeutic targeting of this pathway may prove beneficial, especially in younger patients where maintaining fertility is important.
大约10%至15%的浆液性卵巢肿瘤属于低恶性潜能（LMP）肿瘤类别。与浸润性肿瘤一样，LMP肿瘤可能与卵巢外疾病相关，例如在腹膜腔和区域淋巴结中。然而，与典型的浸润性癌不同，患者通常预后良好。其突变谱也与大多数浆液性癌明显不同。通常，LMP肿瘤与KRAS和BRAF突变相关。对浆液性LMP肿瘤表达谱的研究表明，与高级别卵巢癌相比，RAS-MAPK通路突变总体上具有冗余性，且致癌机制不同。我们的研究结果表明，浆液性LMP中RAS-MAPK通路的激活突变在>70%的病例中存在，而浆液性卵巢癌中约为12.5%。除了KRAS（18%）和BRAF（48%）突变外，ERBB2突变（6%）在浆液性LMP肿瘤中普遍存在，而EGFR则不然。基于我们整个浆液性LMP队列中观察到的表达谱特征，我们提出RAS-MAPK通路激活是浆液性LMP肿瘤发生发展的必要条件，且该通路的其他激活因子尚待确定。重要的是，由于复发性LMP肿瘤的非手术治疗选择很少，针对该通路的治疗靶点可能被证明是有益的，尤其是对年轻患者而言，维持生育能力很重要。
