Vilasi Serena M, Nguyen Jannett, Wang Catherine J, Miao Lingling, Daily Kenneth, Eid Mary, Song Joon Seon, Jiang Hong, Ylaya Kris, Busam Klaus J, Gaiser Maria R, Hewitt Stephen M, Brownell Isaac
Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cancers (Basel). 2024 Feb 15;16(4):788. doi: 10.3390/cancers16040788.
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)常用于区分MCC与SCLC;然而,这些标志物的敏感性和特异性有限。为了识别新的诊断标志物,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MCC的无调性BHLH转录因子1(ATOH1)和转录因子AP-2β(TFAP2B),以及SCLC的癌胚抗原细胞粘附分子6(CEACAM6)。对43例MCC和59例SCLC样本进行了CK20、TTF-1和新候选标志物的免疫染色。所有三种MCC标志物均敏感且特异,CK20和ATOH1染色43/43(100%)例MCC和0/59(0%)例SCLC,TFAP2B染色40/43(93%)例MCC和0/59(0%)例SCLC。TTF-1染色47/59(80%)例SCLC和1/43(2%)例MCC。CEACAM6染色49/59(83%)例SCLC和0/43(0%)例MCC。联合使用CEACAM6和TTF-1可将SCLC检测的敏感性提高到93%,特异性提高到98%。这些数据表明,应探索将ATOH1、TFAP2B和CEACAM6作为区分MCC和SCLC的标志物。