Persistence of Bronchial Dysplasia Is Associated with Development of Invasive Squamous Cell Carcinoma.
Persistence of Bronchial Dysplasia Is Associated with Development of Invasive Squamous Cell Carcinoma.
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DOI：
10.1158/1940-6207.capr-15-0305
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Franklin WA
中科院分区：
文献类型：
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作者：
Merrick DT;Gao D;Miller YE;Keith RL;Baron AE;Feser W;Kennedy TC;Blatchford PJ;Braudrick S;Hirsch FR;Heasley L;Bunn PA Jr;Franklin WA
支气管异型增生(BD)被认为是肺鳞状细胞癌(SCC)的先兆，很少进展为浸润性癌。科罗拉多大学的一个高危队列提供了一个机会，可以在连续的支气管镜检查中直接采样绘制位置的呼吸道上皮。我们假设，持续性的不典型增生病变在后续活检中表现为类似或更高水平的不典型增生，与发生鳞状细胞癌的风险增加有关。188名高危受试者的内窥镜活检按照WHO当前的BD分类进行组织学分类，组织学评分范围为1-8，代表正常的支气管粘膜到浸润性肺癌。根据临床、组织学和免疫组织化学变量对不同部位的随访组织学评分的差异进行比较。持续或进展到高度不典型增生的部位频率较高的受试者(≥37.5%持续/进展，N=35比<；37.5%持续/进展，N=114)与发生侵袭性鳞状细胞癌的发生显著相关(调整风险比：7.84；95%可信区间：1.56，39.39)，发生肺鳞状细胞癌的患者调整后的平均随访组织学评分比非肺癌患者高1.55个单位。目前吸烟、Ki-67生长分数升高、血管形成性鳞状上皮异型增生(ASD)的组织学特征以及基线活检中较高的组织学评分与随访组织学评分的增加显著相关。这些结果表明，持续性BD与侵袭性鳞癌的发生有关。此外，Ki-67的高表达、血管新生改变的存在和基线异型性的程度与BD的持久性有关。
Bronchial dysplasia (BD), a presumed precursor of pulmonary squamous cell carcinoma (SCC), rarely progresses to invasive cancer. A high risk cohort at the University of Colorado provided an opportunity to directly sample airway epithelium at mapped sites on successive bronchoscopies. We have hypothesized that persistent dysplastic lesions showing a similar or higher level of dysplasia on follow-up biopsy, are associated with increased risk for the development of SCC. Endoscopic biopsies from 188 high risk subjects were histologically classified according to the current WHO classification for BD utilizing a numeric histology score ranging from 1-8 representing normal bronchial mucosa through invasive lung cancer. Differences in follow-up histology scores were compared between sites classified by clinical, histologic and immunohistochemical variables. Subjects with a higher frequency of sites that persist or progress to high grade dysplasia (≥37.5% persist/progress, N=35 versus <37.5% persist/progress, N=114) show a significant association with development of incident invasive SCC (adjusted hazard ratio: 7.84; 95% confidence interval: 1.56, 39.39), and those with incident lung SCC have adjusted mean follow-up histology scores 1.55 units higher than in subjects without lung cancer. Current smoking, elevated Ki-67 growth fraction, histologic features of angiogenic squamous dysplasia (ASD) and higher histology score in baseline biopsies are significantly associated with increased follow up histology scores. These results show that persistent BD is associated with the development of invasive SCC. Furthermore, increased expression of Ki-67, the presence of angiogenic change and degree of baseline atypia are associated with persistence of BD.