Hansel Donna E, House Michael G, Ashfaq Raheela, Rahman Ayman, Yeo Charles J, Maitra Anirban
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Int J Gastrointest Cancer. 2003;33(2-3):141-7. doi: 10.1385/IJGC:33:2-3:141.
MAGE1 was originally isolated from human melanoma cells as a target antigen for autologous cytotoxic T lymphocytes. Expression of MAGE1 has subsequently been identified in a number of neoplastic cell types, including testicular germ cell and breast cancer cells, which has led to the development of antitumor MAGE1 vaccines.
To determine if Mage-1 is expressed in pancreatic endocrine neoplasms (PENs) and PEN metastases.
We utilized immunolabeling analysis for Mage-1 on 49 primary PENs, 11 liver metastases, and 6 lymph node metastases. A semiquantitative labeling index (LI) of 0 (no expression), 1, 2 (moderate expression), and 3 (intense expression, correlating with internal control markers) was used to determine relative amounts of MAGE1 expression in these lesions.
We have identified MAGE1 expression in a subset (42 of 49; 86%) of PENs. Normal pancreatic ducts, present in tissue adjacent to PENs, were utilized as a positive control for Mage-1 immunolabeling (index score 3); no other detectable labeling for Mage-1 was evident in normal pancreatic tissue. Primary PENs, with or without metastases (mean LI score 1.2 vs 1.0, respectively), did not demonstrate a significant difference in Mage-1 LI, although intratumoral heterogeneity was apparent in some, but not all, of these lesions. Lymph node metastases (mean score 2.0) demonstrated a significant increase in Mage-1 LI as compared to primary, non-metastatic lesions (p = 0.04984) and primary metastatic lesions (p = 0.02351). In contrast, six patients with a survival of less than one year demonstrated a low Mage-1 LI (mean score, 0.58).
MAGE1 expression is present in a subset of primary PENs and in lymph node metastases, and may therefore serve as a useful marker and potential therapeutic target in PENs. Furthermore, the absence of Mage-1 expression in a subset of primary PENs may indicate a worsened prognosis.
MAGE1最初是从人黑色素瘤细胞中分离出来的,作为自体细胞毒性T淋巴细胞的靶抗原。随后在多种肿瘤细胞类型中发现了MAGE1的表达,包括睾丸生殖细胞和乳腺癌细胞,这促使了抗肿瘤MAGE1疫苗的研发。
确定Mage-1在胰腺内分泌肿瘤(PENs)及其转移灶中是否表达。
我们对49例原发性PENs、11例肝转移灶和6例淋巴结转移灶进行了Mage-1免疫标记分析。采用半定量标记指数(LI),0(无表达)、1、2(中度表达)和3(强表达,与内对照标记相关)来确定这些病变中MAGE1表达的相对量。
我们在一部分(49例中的42例;86%)PENs中发现了MAGE1表达。PENs相邻组织中的正常胰管用作Mage-1免疫标记的阳性对照(指数评分3);在正常胰腺组织中未发现其他可检测到的Mage-1标记。原发性PENs,无论有无转移(平均LI评分分别为1.2和1.0),Mage-1 LI无显著差异,尽管在部分(但不是全部)这些病变中存在瘤内异质性。与原发性非转移病变(p = 0.04984)和原发性转移病变(p = 0.02351)相比,淋巴结转移灶(平均评分2.0)的Mage-1 LI显著增加。相比之下,6例生存期少于1年的患者Mage-1 LI较低(平均评分,0.58)。
MAGE1表达存在于一部分原发性PENs及其淋巴结转移灶中,因此可能作为PENs的有用标记物和潜在治疗靶点。此外,一部分原发性PENs中Mage-1表达的缺失可能预示预后较差。