Beer T W, Rowlands D C, Crocker J
Department of Histopathology, General Hospital, Birmingham, UK.
Thorax. 1996 May;51(5):526-9. doi: 10.1136/thx.51.5.526.
The multidrug resistance marker P-glycoprotein (P-gp) was studied immunohistochemically in 78 primary malignant lung tumours. P-gp is a 170 kD transmembrane ATP dependent drug efflux pump which has been shown to be important in the resistance of some tumours to chemotherapy. Certain normal tissues express P-gp and tumours derived from these tissues are often insensitive to cytotoxic agents, showing raised P-gp levels innately or following chemotherapy or radiotherapy.
Samples from 78 patients undergoing surgery for primary malignant lung tumours were snap frozen and stained immunohistochemically using the monoclonal antibody C219 which reacts with a P-gp epitope. None of the study group had received chemotherapy or radiotherapy before surgery was performed.
Twenty seven of the 78 lung tumours (34.6%) showed immunohistochemically detectable levels of P-gp which varied with tumour type; 17 of 54 squamous cell carcinomas (31.5%), seven of 15 adenocarcinomas (46.7%), and neither of two small cell carcinomas showing positive staining. In six of seven cases normal respiratory epithelium present showed the presence of P-gp.
P-gp is immunohistochemically detectable in frozen tissue from a proportion of malignant lung tumours before exposure to radiotherapy or drugs associated with multidrug resistance. It may have a role in tumour resistance to cytotoxic drugs, but further clinical studies will be required to evaluate any correlation between P-gp levels and response to treatment.
采用免疫组织化学方法对78例原发性恶性肺肿瘤中的多药耐药标志物P - 糖蛋白(P - gp)进行了研究。P - gp是一种170kD的跨膜ATP依赖性药物外排泵,已证明其在某些肿瘤对化疗的耐药性中起重要作用。某些正常组织表达P - gp,源自这些组织的肿瘤通常对细胞毒性药物不敏感,其P - gp水平在化疗或放疗前就已升高或在化疗或放疗后升高。
对78例接受原发性恶性肺肿瘤手术的患者的样本进行速冻,并使用与P - gp表位反应的单克隆抗体C219进行免疫组织化学染色。研究组中无一例患者在手术前接受过化疗或放疗。
78例肺肿瘤中有27例(34.6%)免疫组织化学检测到P - gp水平,其水平因肿瘤类型而异;54例鳞状细胞癌中有17例(31.5%),15例腺癌中有7例(46.7%),而2例小细胞癌均未显示阳性染色。在7例有正常呼吸道上皮的病例中,有6例显示存在P - gp。
在未接触放疗或与多药耐药相关药物之前,一部分恶性肺肿瘤的冷冻组织中可通过免疫组织化学检测到P - gp。它可能在肿瘤对细胞毒性药物的耐药性中起作用,但需要进一步的临床研究来评估P - gp水平与治疗反应之间的任何相关性。