Abstract:
Merkel cell carcinoma (MCC) and small cell lung cancer (SCLC) can be histologically similar. Immunohistochemistry (IHC) for cytokeratin 20 (CK20) and thyroid transcription factor 1 (TTF-1) are commonly used to differentiate MCC from SCLC; however, these markers have limited sensitivity and specificity. To identify new diagnostic markers, we performed differential gene expression analysis on transcriptome data from MCC and SCLC tumors. Candidate markers included atonal BHLH transcription factor 1 (ATOH1) and transcription factor AP-2β (TFAP2B) for MCC, as well as carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) for SCLC. Immunostaining for CK20, TTF-1, and new candidate markers was performed on 43 MCC and 59 SCLC samples. All three MCC markers were sensitive and specific, with CK20 and ATOH1 staining 43/43 (100%) MCC and 0/59 (0%) SCLC cases and TFAP2B staining 40/43 (93%) MCC and 0/59 (0%) SCLC cases. TTF-1 stained 47/59 (80%) SCLC and 1/43 (2%) MCC cases. CEACAM6 stained 49/59 (83%) SCLC and 0/43 (0%) MCC cases. Combining CEACAM6 and TTF-1 increased SCLC detection sensitivity to 93% and specificity to 98%. These data suggest that ATOH1, TFAP2B, and CEACAM6 should be explored as markers to differentiate MCC and SCLC.
摘要:
默克尔细胞癌(MCC)和小细胞肺癌(SCLC)在组织学上可以相似。细胞角蛋白20(CK20)和甲状腺转录因子1(TTF-1)的免疫组织化学(IHC)通常用于区分MCC和SCLC;然而,这些标记物具有有限的灵敏度和特异性。为了识别新的诊断标记,我们对MCC和SCLC肿瘤的转录组数据进行了差异基因表达分析.候选标记包括MCC的无调性BHLH转录因子1(ATOH1)和转录因子AP-2β(TFAP2B),以及用于SCLC的癌胚抗原细胞粘附分子6(CEACAM6)。对43个MCC和59个SCLC样品进行CK20、TTF-1和新候选标记的免疫染色。所有三个MCC标记都是敏感和特异性的,以CK20和ATOH1染色43/43(100%)MCC和0/59(0%)SCLC病例和TFAP2B染色40/43(93%)MCC和0/59(0%)SCLC病例。TTF-1染色47/59(80%)SCLC和1/43(2%)MCC病例。CEACAM6染色49/59(83%)SCLC和0/43(0%)MCC病例。CEACAM6和TTF-1的组合将SCLC检测灵敏度提高到93%,特异性提高到98%。这些数据表明ATOH1、TFAP2B、应探索CEACAM6作为区分MCC和SCLC的标志物。