Cappello Francesco, Di Stefano Antonino, David Sabrina, Rappa Francesco, Anzalone Rita, La Rocca Giampiero, D'Anna Silvestro E, Magno Francesca, Donner Claudio F, Balbi Bruno, Zummo Giovanni
Institute of Human Anatomy, University of Palermo, Palermo, Italy.
Cancer. 2006 Nov 15;107(10):2417-24. doi: 10.1002/cncr.22265.
The relation between smoking, chronic obstructive pulmonary disease (COPD), and lung cancer (LC) is an open field of investigation. A higher frequency of adenocarcinoma has been reported in patients with COPD. Heat shock proteins (Hsps) are implicated in tumoral cell growth and differentiation. The aim of the present study was to investigate the expression of Hsp60 and Hsp10 in bronchial biopsies from smokers with COPD and in 10 lung cancer patients and to evaluate the association between Hsps expression and carcinogenetic steps of LC.
An immunohistochemical study was performed for Hsp60 and Hsp10 in bronchial biopsies from 35 COPD (postbronchodilator forced expiratory volume in 1 second [FEV(1)]: 53 +/- 19% [mean +/- SD]) patients with a history of smoking (53 +/- 34 pack/years) and in 10 patients with adenocarcinoma or adenosquamous carcinoma (ASC). Immunopositivity was quantified in the bronchial epithelium and in specimens with ASC. RESULTS.: In smokers with COPD, 10 out of 35 patients had a normal bronchial epithelium (NBE), 12 showed basal cell hyperplasia (BCH), 5 squamous metaplasia (SM), and 8 dysplasia (Dy). It was found that 58 +/- 23% and 54 +/- 23% of NBE and 48 +/- 29% and 52 +/- 26% of BCH expressed Hsp60 and Hsp10, respectively; in contrast, only 3 +/- 3% and 3.6 +/- 2% of SM, 1.9 +/- 4% and 1.1 +/- 2% of Dy expressed Hsp60 and Hsp10, respectively. ASC specimens were negative for Hsps proteins. Interestingly, NBE also present at the edges of ASC specimens was negative for Hsps proteins.
The loss of Hsp60 and Hsp10 immunopositivity is related to the development and progression of bronchial cancer in smokers with COPD.
吸烟、慢性阻塞性肺疾病（COPD）与肺癌（LC）之间的关系是一个有待深入研究的领域。据报道，COPD患者腺癌的发生率较高。热休克蛋白（Hsps）与肿瘤细胞的生长和分化有关。本研究旨在调查慢性阻塞性肺疾病吸烟者支气管活检组织及10例肺癌患者中Hsp60和Hsp10的表达情况，并评估热休克蛋白表达与肺癌致癌步骤之间的关联。
对35例有吸烟史（53±34包/年）的COPD患者（支气管扩张后1秒用力呼气量[FEV(1)]：53±19%[平均值±标准差]）的支气管活检组织以及10例腺癌或腺鳞癌（ASC）患者进行Hsp60和Hsp10的免疫组织化学研究。对支气管上皮和ASC标本中的免疫阳性进行定量分析。结果：在患有COPD的吸烟者中，35例患者中有10例支气管上皮正常（NBE），12例表现为基底细胞增生（BCH），5例为鳞状化生（SM），8例为发育异常（Dy）。结果发现，NBE中分别有58±23%和54±23%、BCH中分别有48±29%和52±26%表达Hsp60和Hsp10；相比之下，SM中分别只有3±3%和3.6±2%、Dy中分别只有1.9±4%和1.1±2%表达Hsp60和Hsp10。ASC标本中热休克蛋白呈阴性。有趣的是，ASC标本边缘的NBE热休克蛋白也呈阴性。
Hsp60和Hsp10免疫阳性的缺失与患有COPD的吸烟者支气管癌的发生和发展有关。
