Tanner M, Järvinen P, Isola J
Laboratory of Cancer Genetics, Institute of Medical Technology, Tampere University and Tampere University Hospital, FIN-33014 Tampere, Finland.
Cancer Res. 2001 Jul 15;61(14):5345-8.
Amplification of the HER-2/neu oncogene and amplification of the topoisomerase IIalpha gene are important determinators of the response to chemotherapy in advanced breast cancer. Assays of these genes are usually carried out using primary tumor samples, because biopsies from metastatic lesions are not usually taken. We studied the concordance of Her-2/neu and topoisomerase IIalpha amplification in primary breast tumors and their metastases by immunostaining and DNA in situ hybridization. HER-2/neu amplification, present in 28% of the primary tumors (n = 46), was always associated with amplification in its metastasis. Conversely, no metastases with HER-2/neu amplification were seen without amplification in the primary tumor. Topoisomerase IIalpha gene copy status (amplification/deletion/unaltered) remained generally unchanged in HER-2/neu-positive tumors, but in three cases, the predominant cell population in metastatic tissue was present only as a subpopulation in the primary tumor. We conclude that amplification of HER-2/neu measured in primary tumor reflects the status of metastases. Minor discrepancies between primary and metastatic tumors in topoisomerase IIalpha gene copy status may reflect evolvement of the amplicon structure in successive cell divisions.
HER-2/neu癌基因的扩增以及拓扑异构酶IIα基因的扩增是晚期乳腺癌化疗反应的重要决定因素。这些基因的检测通常使用原发性肿瘤样本进行，因为通常不会采集转移病灶的活检样本。我们通过免疫染色和DNA原位杂交研究了原发性乳腺肿瘤及其转移灶中Her-2/neu和拓扑异构酶IIα扩增的一致性。HER-2/neu扩增存在于28%的原发性肿瘤中（n = 46），其转移灶中总是伴有扩增。相反，在原发性肿瘤无扩增的情况下，未见有HER-2/neu扩增的转移灶。在HER-2/neu阳性肿瘤中，拓扑异构酶IIα基因拷贝状态（扩增/缺失/未改变）总体保持不变，但在3例中，转移组织中的主要细胞群体在原发性肿瘤中仅作为亚群体存在。我们得出结论，在原发性肿瘤中检测到的HER-2/neu扩增反映了转移灶的状态。原发性肿瘤和转移瘤在拓扑异构酶IIα基因拷贝状态上的微小差异可能反映了在连续细胞分裂中扩增子结构的演变。
