Zborovskaya I, Gasparian A, Kitaeva M, Polotzky B, Tupitzin N, Machaladze Z, Gerasimov S, Shtutman M, Jakubovskaya M, Davidov M, Tatosyan A
Blokhin's Cancer Research Center of Medical Science Academy, Moscow, Russia.
Clin Exp Metastasis. 1996 Nov;14(6):490-500. doi: 10.1007/BF00115109.
The restriction fragment length polymorphism of c-Ha-ras-1 and L-myc genes and expression of cell surface effector molecules were studied to determine their potential utility as markers for assessing risk of metastasis in 84 lung cancer patients. We performed a comparative study of primary lung carcinomas, metastases, adjacent tissues and blood samples in a group of patients with lung cancer of different histological types, grade of differentiation and presence of regional and distant metastasis. No differences in the frequency of c-Ha-ras-1 rare alleles were found between lung cancer patients and unaffected controls. The detection of common a4-allele seems to be associated with metastasis and low differentiation of lung carcinomas. S-allele of L-myc was observed in 82.6% of patients with metastatic lesions. Homozygosity of L-allele patients was not evidence for distant metastasis and only 17.4% of these patients have metastatic lesions of the lymph nodes. The expression of HLA class I and receptor of transferrin (TrRec) were tested immunohistochemically in the same patients. In the group of squamous cell carcinomas with regional metastases the expression of HLA class I antigens was decreased [7/21 (33.3%) positive staining tumors versus 13/20 (65.0%) in the group without metastases]. The opposite situation was observed for TrRec. The data of restriction fragment length polymorphism of oncogenes and expression of two cell surface effector molecules, identified in the same patients, were combined. The registration of more than one poor marker, tested in individuals with squamous cell carcinoma, closely correlated with dissemination and advanced stage of the disease. Nearly 90% (20/22) of patients with well and moderately differentiated tumor revealed metastatic lesions versus 6.6% (1/15) of patients with manifestation of a single poor marker. Finally, proposals could be made for the development of a risk group that incorporates both clinical and molecular biology features in the prediction of metastasis.
为了确定c-Ha-ras-1和L-myc基因的限制性片段长度多态性及细胞表面效应分子的表达在评估84例肺癌患者转移风险方面的潜在效用，我们进行了相关研究。我们对一组不同组织学类型、分化程度以及有无区域和远处转移的肺癌患者的原发性肺癌、转移灶、邻近组织和血液样本进行了比较研究。肺癌患者与未受影响的对照组之间，c-Ha-ras-1稀有等位基因的频率没有差异。常见的a4等位基因的检测似乎与肺癌的转移和低分化有关。在82.6%的有转移灶的患者中观察到L-myc的S等位基因。L等位基因患者的纯合性并非远处转移的证据，这些患者中只有17.4%有淋巴结转移灶。我们对同一组患者进行了免疫组织化学检测，以检测HLA I类分子和转铁蛋白受体（TrRec）的表达。在有区域转移的鳞状细胞癌组中，HLA I类抗原的表达降低[7/21（33.3%）肿瘤呈阳性染色，而无转移组为13/20（65.0%）]。TrRec的情况则相反。我们将在同一患者中鉴定的癌基因限制性片段长度多态性数据和两种细胞表面效应分子的表达数据进行了合并。在鳞状细胞癌患者中检测到不止一种不良标志物，这与疾病的播散和晚期密切相关。高分化和中分化肿瘤患者中近90%（20/22）出现转移灶，而仅有单一不良标志物表现的患者中这一比例为6.6%（1/15）。最后，可以提出关于建立一个在转移预测中纳入临床和分子生物学特征的风险组的建议。
