Yaghmour George, Prouet Philippe, Wiedower Eric, Jamy Omer Hassan, Feldman Rebecca, Chandler Jason C, Pandey Manjari, Martin Mike G
The West Cancer Center, 1588 Union Ave., Memphis, TN, 38104, USA.
Department of Hematology & Oncology, The University of Tennessee Health Science Center, 956 Court Ave., Suite H310A, Memphis, TN, 38163, USA.
J Ovarian Res. 2016 Aug 26;9(1):52. doi: 10.1186/s13048-016-0259-2.
As we have previously reported, small cell carcinoma of the ovary (SCCO) is a rare, aggressive form of ovarian cancer associated with poor outcomes. In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCO.
Patients with SCCO, SCCO-HT (hypercalcemic type), neuroendocrine tumors of the ovary (NET-O), and small cell carcinoma of the lung (SCLC) profiled by Caris Life Sciences between 2007-2015 were identified. Tumors were assessed with up to 21 IHC stains, in situ hybridization of cMET, EGFR, HER2 and PIK3CA, and next-generation sequencing (NGS) as well as Sanger sequencing of selected genes.
Forty-six patients with SCCO (10 SCCO, 18 SCCO-HT, 18 NET-O) were identified as well as 58 patients with SCLC for comparison. Patients with SCCO and SCCO-HT were younger (median 42 years [range 12-75] and 26 years [range 8-40], respectively) than patients with NET-O 62 [range 13-76] or SCLC 66 [range 36-86]. SCCO patients were more likely to be metastatic (70 %) than SCCO-HT (50 %) or NET-O (33 %) patients, but at a similar rate to SCLC patients (65 %). PD1 expression varied across tumor type with SCCO (100 %), SCCO-HT (60 %), NET-O (33 %) vs SCLC (42 %). PDL1 expression also varied with SCCO (50 %), SCCO-HT (20 %), NET-O (33 %) and SCLC (0 %). No amplifications were identified in cMET, EGFR, or HER2 and only 1 was found in PIK3CA (NET-O). Actionable mutations were rare with 1 patient with SCCO having a BRCA2 mutation and 1 patient with NET-O having a PIK3CA mutation. No other actionable mutations were identified.
No recurrent actionable mutations or rearrangements were identified using this platform in SCCO. IHC patterns may help guide the use of chemotherapy in these rare tumors.
正如我们之前所报道的，卵巢小细胞癌（SCCO）是一种罕见的、侵袭性的卵巢癌形式，预后较差。为了确定新的治疗方案，我们利用综合基因组分析来评估SCCO中新型疗法的潜力。
确定了2007年至2015年间由Caris生命科学公司进行分析的SCCO、SCCO-HT（高钙血症型）、卵巢神经内分泌肿瘤（NET-O）和肺小细胞癌（SCLC）患者。使用多达21种免疫组化染色、cMET、EGFR、HER2和PIK3CA的原位杂交、下一代测序（NGS）以及选定基因的桑格测序对肿瘤进行评估。
确定了46例SCCO患者（10例SCCO、18例SCCO-HT、18例NET-O）以及58例SCLC患者用于比较。SCCO和SCCO-HT患者比NET-O患者（中位年龄62岁[范围13 - 76岁]）或SCLC患者（中位年龄66岁[范围36 - 86岁]）更年轻（分别为中位年龄42岁[范围12 - 75岁]和26岁[范围8 - 40岁]）。SCCO患者比SCCO-HT（50%）或NET-O（33%）患者更易发生转移（70%），但与SCLC患者（65%）的转移率相似。PD1表达因肿瘤类型而异，SCCO为（100%）、SCCO-HT为（60%）、NET-O为（33%），而SCLC为（42%）。PDL1表达也因肿瘤类型而异，SCCO为（50%）、SCCO-HT为（20%）、NET-O为（33%），SCLC为（0%）。在cMET、EGFR或HER2中未发现扩增，仅在PIK3CA（NET-O）中发现1例扩增。可操作的突变很少见，1例SCCO患者有BRCA2突变，1例NET-O患者有PIK3CA突变。未发现其他可操作的突变。
使用该平台在SCCO中未发现复发性可操作的突变或重排。免疫组化模式可能有助于指导这些罕见肿瘤的化疗应用。
