Chang Hee-Kyung, Park JongWook, Kim WooGyeong, Kim KiTae, Lee Minyoung, Park UnDong, Choi ByungGil
Department of Pathology, Kosin University Medical College, 34 AmNam-Dong, Suh-Ku, Pusan 602-702, South Korea.
Gynecol Oncol. 2005 May;97(2):342-7. doi: 10.1016/j.ygyno.2004.12.051.
Melanoma antigen genes (MAGE) and GAGE genes are encoded by genes that are silent in virtually all normal adult tissues but are expressed in tumors from various tissues. These gene products are targets for specific immunotherapy as they are presented by HLA I molecules and recognized by autologous cytotoxic T-lymphocytes. However, the characteristics of these genes, especially in uterine cervical cancer are relatively unknown.
This study evaluated the prevalence of MAGE and GAGE by reverse transcription-polymerase chain reaction (RT-PCR) with common primers and discusses clinical implications in cervical carcinoma.
Fresh tissue from 37 cases of primary squamous cell carcinoma and normal cervical mucosa were evaluated for clinicopathologic parameters including Human Papilloma Virus (HPV)-16,18 infection by PCR, tumor stage by FIGO classification and lymph node involvement. RT-nested PCR for the MAGE and GAGE genes was performed with common primers and DNA sequencing after subcloning was used for identification of PCR products of MAGE. Formalin-fixed paraffin embedded material from the same specimen was analyzed by in situ RT-PCR for MAGE.
Expression of MAGE and GAGE was not observed in normal tissues. Eleven out of 37 cases expressed MAGE mRNA (29.7%): analysis of subtypes identified one case of MAGE-1, two cases of MAGE-4b, six cases of MAGE-3, and two unknown subtypes. Thirteen out of 37 cases (35.1%) expressed GAGE mRNA. No significant relationships between expression of these genes and FIGO staging, lymph node metastasis or HPV infection were found.
Expression of MAGE and GAGE may be involved in the development of uterine cervical carcinoma from intraepithelial neoplasia, although without distinct prognostic significance. MAGE and GAGE genes have the potential to be used as targets for the treatment of uterine cervical carcinoma.
黑色素瘤抗原基因(MAGE)和GAGE基因由在几乎所有正常成人组织中沉默但在各种组织的肿瘤中表达的基因编码。这些基因产物是特异性免疫治疗的靶点,因为它们由HLA I分子呈递并被自体细胞毒性T淋巴细胞识别。然而,这些基因的特征,尤其是在子宫颈癌中的特征相对未知。
本研究通过使用通用引物的逆转录聚合酶链反应(RT-PCR)评估MAGE和GAGE的患病率,并讨论其在宫颈癌中的临床意义。
对37例原发性鳞状细胞癌和正常宫颈黏膜的新鲜组织进行评估,以确定其临床病理参数,包括通过PCR检测人乳头瘤病毒(HPV)-16、18感染,通过国际妇产科联盟(FIGO)分类确定肿瘤分期以及有无淋巴结转移。使用通用引物对MAGE和GAGE基因进行RT巢式PCR,并在亚克隆后进行DNA测序以鉴定MAGE的PCR产物。对同一标本的福尔马林固定石蜡包埋材料进行MAGE的原位RT-PCR分析。
在正常组织中未观察到MAGE和GAGE的表达。37例中有11例表达MAGE mRNA(29.7%):亚型分析确定1例MAGE-1、2例MAGE-4b、6例MAGE-3和2种未知亚型。37例中有13例(35.1%)表达GAGE mRNA。未发现这些基因的表达与FIGO分期、淋巴结转移或HPV感染之间存在显著关系。
MAGE和GAGE的表达可能参与了子宫颈癌从上皮内瘤变的发展过程,尽管没有明显的预后意义。MAGE和GAGE基因有潜力用作子宫颈癌治疗的靶点。