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非小细胞肺癌肿瘤及手术切缘组织中c-myc和p53基因改变的研究及其对临床病理行为的影响:采用荧光原位杂交技术

Investigation of c-myc and p53 gene alterations in the tumor and surgical borderline tissues of NSCLC and effects on clinicopathologic behavior: by the FISH technique.

作者信息

Yakut T, Egeli U, Gebitekin C

机构信息

Department of Medical Biology and Genetics, Faculty of Medicine, University of Uludag, Bursa, Turkey.

出版信息

Lung. 2003;181(5):245-58. doi: 10.1007/s00408-003-1026-x.

Abstract

Genetic alterations on the primary tumoral tissues and surgical borderline tissues of 51 patients with NSCLC on which radiotherapy and chemotherapy had not been performed were analyzed by using the FISH method with locus-specific probes for p53 tumor suppressor gene and c-myc oncogene and centromere-specific probes for chromosome 17 and chromosome 8 on which these genes are located. P53 deletions were detected in 7 patients (13.7%), c-myc amplification in 4 patients (7.8%), monosomy 17 in 2 patients (3.9%) and trisomy 8 in 3 patients (5.8%), and a high level of polyploidy in tumoral tissues of 6 patients (11.7%). P53 deletion and c-myc amplification were found at surgical borderlines of 2 patients and 1 patient, respectively. Although both p53 deletion and c-myc amplification have low frequency at surgical border tissues, not only their detection is important for the follow-up of recurrency and metastasis, but it is also important for genetical and pathological staging. The results of this study show that c-myc amplification in NSCLC is related to the shortening of survival (p < 0.01). C-myc amplification and p53 deletion are also effective for the occurrence of metastasis (p < 0.05) and the effect of c-myc amplification in this matter is much higher than p53 deletion. The gain or loss of copy number of chromosome 8 and monosomy 17 show parallel effects with c-myc amplification and p53 deletion, respectively, on the clinicopathological behavior of tumors.

摘要

采用荧光原位杂交(FISH)方法,使用针对p53肿瘤抑制基因和c-myc癌基因的位点特异性探针以及针对这些基因所在的17号和8号染色体的着丝粒特异性探针,对51例未接受过放疗和化疗的非小细胞肺癌(NSCLC)患者的原发性肿瘤组织和手术切缘组织进行基因改变分析。7例患者(13.7%)检测到p53缺失,4例患者(7.8%)检测到c-myc扩增,2例患者(3.9%)检测到17号染色体单体,3例患者(5.8%)检测到8号染色体三体,6例患者(11.7%)的肿瘤组织中存在高水平多倍体。分别在2例和1例患者的手术切缘发现p53缺失和c-myc扩增。虽然p53缺失和c-myc扩增在手术切缘组织中的发生率较低,但它们的检测不仅对复发和转移的随访很重要,对基因和病理分期也很重要。本研究结果表明,NSCLC中的c-myc扩增与生存期缩短有关(p < 0.01)。c-myc扩增和p53缺失对转移的发生也有影响(p < 0.05),在这方面c-myc扩增的影响远高于p53缺失。8号染色体拷贝数的增加或减少以及17号染色体单体分别与c-myc扩增和p53缺失对肿瘤的临床病理行为具有相似的影响。

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