Blumenthal Rosalyn D, Leon Evelyn, Hansen Hans J, Goldenberg David M
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA.
BMC Cancer. 2007 Jan 3;7:2. doi: 10.1186/1471-2407-7-2.
Many breast, pancreatic, colonic and non-small-cell lung carcinoma lines express CEACAM6 (NCA-90) and CEACAM5 (carcinoembryonic antigen, CEA), and antibodies to both can affect tumor cell growth in vitro and in vivo. Here, we compare both antigens as a function of histological phenotype in breast, pancreatic, lung, ovarian, and prostatic cancers, including patient-matched normal, primary tumor, and metastatic breast and colonic cancer specimens.
Antigen expression was determined by immunohistochemistry (IHC) using tissue microarrays with MN-15 and MN-3 antibodies targeting the A1B1- and N-domains of CEACAM6, respectively, and the MN-14 antibody targeting the A3B3 domain of CEACAM5. IHC was performed using avidin-biotin-diaminobenzide staining. The average score +/- SD (0 = negative/8 = highest) for each histotype was recorded.
For all tumors, the amount of CEACAM6 expressed was greater than that of CEACAM5, and reflected tumor histotype. In breast tumors, CEACAM6 was highest in papillary > infiltrating ductal > lobular > phyllodes; in pancreatic tumors, moderately-differentiated > well-differentiated > poorly-differentiated tumors; mucinous ovarian adenocarcinomas had almost 3-fold more CEACAM6 than serous ovarian adenocarcinomas; lung adenocarcinomas > squamous tumors; and liver metastases of colonic carcinoma > primary tumors = lymph nodes metastases > normal intestine. However, CEACAM6 expression was similar in prostate cancer and normal tissues. The amount of CEACAM6 in metastatic colon tumors found in liver was higher than in many primary colon tumors. In contrast, CEACAM6 immunostaining of lymph node metastases from breast, colon, or lung tumors was similar to the primary tumor.
CEACAM6 expression is elevated in many solid tumors, but variable as a function of histotype. Based on previous work demonstrating a role for CEACAM6 in tumor cell migration, invasion and adhesion, and formation of distant metastases (Blumenthal et al., Cancer Res 65: 8809-8817, 2005), it may be a promising target for antibody-based therapy.
许多乳腺癌、胰腺癌、结肠癌和非小细胞肺癌细胞系表达癌胚抗原相关细胞黏附分子6（CEACAM6，即NCA-90）和癌胚抗原相关细胞黏附分子5（CEACAM5，即癌胚抗原，CEA），针对这两种抗原的抗体均可在体内外影响肿瘤细胞生长。在此，我们比较了这两种抗原在乳腺癌、胰腺癌、肺癌、卵巢癌和前列腺癌中的表达情况，包括患者匹配的正常组织、原发性肿瘤以及转移性乳腺癌和结肠癌标本。
采用免疫组织化学（IHC）方法，使用组织芯片，分别用靶向CEACAM6的A1B1和N结构域的MN-15和MN-3抗体以及靶向CEACAM5的A3B3结构域的MN-14抗体来测定抗原表达。采用抗生物素蛋白-生物素-二氨基联苯胺染色进行免疫组织化学检测。记录每种组织类型的平均评分±标准差（0 = 阴性/8 = 最高）。
对于所有肿瘤，CEACAM6的表达量均高于CEACAM5，且反映肿瘤组织类型。在乳腺肿瘤中，CEACAM6在乳头状癌>浸润性导管癌>小叶癌>叶状肿瘤中表达最高；在胰腺肿瘤中，中度分化>高分化>低分化肿瘤；黏液性卵巢腺癌的CEACAM6表达量几乎是浆液性卵巢腺癌的3倍；肺腺癌>鳞状细胞癌；结肠癌肝转移灶>原发性肿瘤 = 淋巴结转移灶>正常肠组织。然而，前列腺癌和正常组织中CEACAM6的表达相似。在肝脏发现的转移性结肠肿瘤中CEACAM6的表达量高于许多原发性结肠肿瘤。相比之下，乳腺癌、结肠癌或肺癌肿瘤淋巴结转移灶的CEACAM6免疫染色与原发性肿瘤相似。
CEACAM6在许多实体瘤中表达升高，但因组织类型而异。基于先前的研究表明CEACAM6在肿瘤细胞迁移（侵袭和黏附）以及远处转移形成中发挥作用（Blumenthal等人，《癌症研究》65: 8809 - 8817，2005年），它可能是基于抗体治疗的一个有前景的靶点。
