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.
默克尔细胞癌(MCC)与小细胞肺癌(SCLC)在组织学上可能具有相似性。细胞角蛋白20(CK20)和甲状腺转录因子1(TTF-1)的免疫组织化学检测常用于区分MCC与SCLC,但这些标志物的敏感性和特异性有限。为寻找新的诊断标志物,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。候选标志物包括针对MCC的Atonal BHLH转录因子1(ATOH1)和转录因子AP-2β(TFAP2B),以及针对SCLC的癌胚抗原相关细胞黏附分子6(CEACAM6)。对43例MCC和59例SCLC样本进行了CK20、TTF-1及新候选标志物的免疫染色检测。三种MCC标志物均表现出高敏感性和特异性:CK20和ATOH1在43/43例(100%)MCC中呈阳性,在0/59例(0%)SCLC中呈阴性;TFAP2B在40/43例(93%)MCC中呈阳性,在0/59例(0%)SCLC中呈阴性。TTF-1在47/59例(80%)SCLC和1/43例(2%)MCC中呈阳性。CEACAM6在49/59例(83%)SCLC和0/43例(0%)MCC中呈阳性。联合检测CEACAM6与TTF-1可将SCLC的检测敏感性提高至93%,特异性提高至98%。这些数据表明,ATOH1、TFAP2B和CEACAM6可作为区分MCC与SCLC的潜在标志物进行深入研究。