贲门腺癌组织黑色素瘤相关抗原-A9和-A11表达临床意义研究

Expression and clinical significance of melanoma antigen-A9 and A11 in gastric cardiac adenocarcinoma tissues

目的黑色素瘤相关抗原(melanoma antigen,MAGE)在肿瘤的发生发展中起重要作用,而MAGE-A9和MAGE-A11在贲门腺癌组织中表达与临床病理学特征之间的关系仍不清楚。本研究旨在探讨MAGE-A9和MAGE-A11在贲门腺癌组织中的表达,分析其与贲门腺癌患者临床病理学特征及其预后的关系。方法选取河北医科大学第四医院2010-09-15-2010-11-15住院手术切除的贲门腺癌组织及距离癌组织边缘>5cm且外观正常的相应癌旁组织标本各60例,同时选取5例该院同期前列腺癌住院患者术后的睾丸组织作为阳性对照。应用免疫组织化学法检测贲门腺癌组织及相应癌旁组织中MAGE-A9和MAGE-A11蛋白的表达。结果贲门腺癌组织中MAGE-A9和MAGE-A11蛋白的阳性表达率分别为40.0%(24/60)和51.7%(31/60),而相应的癌旁组织未发现MAGE-A9和MAGE-A11蛋白的表达。MAGE-A9蛋白表达与贲门腺癌患者的性别(χ2=0.062,P=0.803)、年龄(χ2=0.179,P=0.673)、临床分期(χ2=2.791,P=0.248)、肿瘤大小(χ2=0.014,P=0.993)和淋巴转移(χ2=0.128,P=0.721)均无相关性,但与组织学分级相关(χ2=10.437,P=0.005)。MAGE-A11蛋白表达与贲门腺癌患者的性别(χ2=0.020,P=0.887)、年龄(χ2=2.530,P=0.190)、肿瘤大小(χ2=2.550,P=0.279)和淋巴转移(χ2=2.550,P=0.110)均无相关性,但与临床分期(χ2=15.095,P=0.001)和组织学分级(χ2=13.424,P=0.001)呈正相关。Log-Rank检验结果显示,MAGE-A9和MAGE-A11蛋白表达阳性的贲门腺癌患者的生存期均显著低于其表达阴性的患者,χ2值分别为5.317和6.082,P值分别为0.021和0.014。Cox多因素分析提示,MAGE-A9蛋白表达(HR=3.304,P=0.015)、MAGE-A11蛋白表达(HR=2.933,P=0.006)、组织学分级(HR=2.018,P=0.034)及临床分期(HR=2.532,P=0.004)可作为整体生存的独立预后因素。结论 MAGE-A9和MAGE-A11蛋白是贲门腺癌的特异性抗原。MAGE-A9和MAGE-A11蛋白可作为贲门腺癌预后不良的预测指标。

[ABSTRACT] OBJECTIVE Melanoma-associated antigen （MAGE） family genes are reported to play important roles in the development of human cancers. However, the relationship between the expression of MAGE-A9,-All and clinico- pathological characteristics in human laryngeal carcinoma remains unclear. The aim of this article was to investigate the expression of MAGE -A9 and -A11 in gastric cardiac adenocarciomas, and analyze the relationship between the expression of MAGE-A9 ,-All protein and their clinical biological indicators and the prognostic factors. METHODS Cancerous （n= 60） and adjacent （n--60） esophageal tissue specimens were collected from 60 patients with gastric cardiac adenocarciomas who were surgically treated in Fourth Hospital of Hebei Medical University between March and June of 2010. Testicular tissues（n= 5） were collected from men with prostate cancer as the positive control in the same time. Para-carcinoma tissues＇ edge were more than 5 cm distance away from cancer tissues and looking normal, lmmunohistochemical staining was performed to assess the expression of MAGE-A9 and MAGE-All in carcinoma and adjacent tissues. RESULTS MAGE-A9 and -All protein were not expressed in adjacent tissues, the positive rates of MAGE-A9 and -All protein in carcinoma were 40.0% （24/60） and 51.7%（31/60） respectively. The expression of MAGE-A9 protein was not related to the gender（X^2=0. 062,P=0. 803）, age（X^2 =0. 179, P=0. 673）, clinical stage（X^2=2. 791, P=0. 248）, tumor size（X^2=0.014, P=0. 993） and lymph node metastasis （X^2= 0. 128, P = 0.721） in patients with gastric cardiac adenocarciomas, while histological grade（X^2=10.37, P=0. 005） were related to the expression of MAGE-A9 protein. The expression of MAGE-All protein was not related to the gender（X^2=0. 020,P=0. 887）, age（X^2=2. 530, P=0. 190）, tumor size（X^2=2. 550, P = 0. 279） and lymph node metastasis （X^2=2. 550, P = 0. 110） in patients with gastric cardiac adenocarciomas, while clinical stage （X^2=15.095, P = 0. 00 ] ） and histological grade （X^2=13. 424, P=0.001 ） were positively related to the expression of MAGE All protein. Log-rank test showed that the survival time of MAGE-A9 （X^2=5. 317, P= 0. 021） and -All （X^2=6. 082, P= 0. 014） expression were lower than those negative ones in patients with gastric cardiac adenocarciomas. Cox multivariate analysis suggested that MAGE-A9 protein expression （HR= 3. 304, P= 0. 015）, MAGE-A11 pro-tein expression （HR=2. 933,P=0. 006）, histological grade （HR=2. 018, P=0. 034） and TNM stage （HR=2. 532, P=0. 004） may serve as independent prognostic factors for overall survival. CONCLUSIONS MAGE-A9 and -All pro- teins are gastric cardiac adenocarcioma specific antigens. They may be important markers for poor prognosis of gastric cardiac adenocarciomas.