对高级别骨肉瘤患者原发性肿瘤和异时性肺转移灶中P-糖蛋白、HER-2/ErbB-2、p53和Bcl-2的评估。

Evaluation of P-glycoprotein, HER-2/ErbB-2, p53, and Bcl-2 in primary tumor and metachronous lung metastases in patients with high-grade osteosarcoma.

作者信息

Ferrari Stefano, Bertoni Franco, Zanella Licciana, Setola Elisabetta, Bacchini Patrizia, Alberghini Marco, Versari Michela, Bacci Gaetano

机构信息

Chemotherapy Service, Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Bologna, Italy.

出版信息

Cancer. 2004 May 1;100(9):1936-42. doi: 10.1002/cncr.20151.

DOI:10.1002/cncr.20151

PMID:15112275

Abstract

BACKGROUND

Investigation of the relation between primary tumor and metastatic disease is necessary for the identification of predictive factors for postrecurrence survival (PRS) in patients with recurrent osteosarcoma.

METHODS

Cellular levels of P-glycoprotein, ErbB-2, p53, and Bcl-2 expression were evaluated in primary tumor biopsy and metachronous pulmonary metastasis specimens from 19 patients with high-grade osteosarcoma. Results were analyzed for differences between primary tumor and pulmonary metastases and for correlations between expression patterns and survival.

RESULTS

Positive staining in lung metastases was noted in 68%, 53%, 32%, and 84% of patients for P-glycoprotein, ErbB-2, p53, and Bcl-2, respectively. These percentages were higher than those observed in primary tumor specimens for all genetic markers evaluated, with a significant difference in the percentage of patients with positive staining for P-glycoprotein (68% vs. 32%; P = 0.05) and a near-significant difference in the percentage of patients with positive staining for Bcl-2 (84% vs. 53%; P = 0.08). Patients with ErbB-2 expression in the primary tumor were more likely to have multiple metastases and shorter recurrence-free intervals compared with patients in whom ErbB-2 expression was not observed, whereas differences in P-glycoprotein, p53, and Bcl-2 expression were not related to differences in metastatic pattern. PRS was influenced by p53 expression levels in pulmonary metastases, with patients who had negative staining for p53 having a significantly better PRS rate relative to patients with positive staining for p53 (3-year PRS rate: p53-negative, 64%; p53-positive, 17%; P = 0.008).

CONCLUSIONS

In the current study of patients with high-grade osteosarcoma, most patients exhibited increased cellular expression of P-glycoprotein, ErbB-2, and Bcl-2 in recurrent pulmonary metastases compared with primary tumor. Further studies aimed at investigating the relation between altered p53 expression in lung metastases and postrecurrence survival are recommended.

摘要

背景

对于复发性骨肉瘤患者，研究原发性肿瘤与转移性疾病之间的关系对于确定复发后生存（PRS）的预测因素是必要的。

方法

评估了19例高级别骨肉瘤患者原发性肿瘤活检标本和异时性肺转移标本中P-糖蛋白、ErbB-2、p53和Bcl-2的细胞表达水平。分析结果以比较原发性肿瘤与肺转移之间的差异以及表达模式与生存之间的相关性。

结果

在肺转移中，P-糖蛋白、ErbB-2、p53和Bcl-2染色阳性的患者分别占68%、53%、32%和84%。对于所有评估的基因标志物，这些百分比均高于原发性肿瘤标本中的观察值，其中P-糖蛋白染色阳性患者的百分比有显著差异（68%对32%；P = 0.05），Bcl-2染色阳性患者的百分比有接近显著差异（84%对53%；P = 0.08）。与未观察到ErbB-2表达的患者相比，原发性肿瘤中表达ErbB-2的患者更有可能发生多发转移且无复发生存期更短，而P-糖蛋白、p53和Bcl-2表达的差异与转移模式的差异无关。PRS受肺转移中p53表达水平的影响，p53染色阴性的患者相对于p53染色阳性的患者具有显著更好的PRS率（3年PRS率：p53阴性，64%；p53阳性，17%；P = 0.008）。