VU University Medical Center, Department of Pathology, De Boelelaan 1117, Amsterdam, The Netherlands.
Am J Respir Crit Care Med. 2011 Oct 15;184(8):948-56. doi: 10.1164/rccm.201102-0218OC. Epub 2011 Jul 28.
Autofluorescence bronchoscopy (AFB) is a valid strategy for detecting premalignant endobronchial lesions. However, no biomarker can reliably predict lung cancer risk of subjects with AFB-visualized premalignant lesions.
The present study set out to identify AFB-visualized squamous metaplastic (SqM) lesions with malignant potential by DNA copy number profiling.
Regular AFB examinations in 474 subjects at risk of lung cancer identified six subjects with SqM lesions at baseline, and carcinoma in situ or carcinoma (carcinoma in situ or greater) at the initial SqM site at follow-up bronchoscopy. These progressive SqM lesions were compared for immunostaining pattern and array comparative genomic hybridization-based chromosomal profiles with 23 SqM lesions of subjects who remained cancer-free. Specific DNA copy number alterations (CNAs) linked to cancer risk were identified and accuracy of CNAs to predict endobronchial cancer in this series was determined.
At baseline, p53, p63, and Ki-67 immunostaining were not predictive for a differential clinical outcome of SqM lesions. The mean number of CNAs in baseline SqM of cases was significantly higher compared with control subjects (P < 0.01). Chromosomal regions significantly more frequently altered in SqM of cases were 3p26.3-p11.1, 3q26.2-q29, 9p13.3-p13.2, and 17p13.3-p11.2 (family-wise error rate <0.10). CNAs were specifically detected at the site of future cancer. In cases, baseline-detected CNAs persisted in subsequent biopsies taken from the initial site, and levels increased toward cancer progression. In this series, a model based on CNAs at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3 predicted cancer with 97% accuracy.
The data suggest that the presence of specific CNAs in SqM lesions predict endobronchial cancer.
自体荧光支气管镜检查（AFB）是一种检测癌前支气管内病变的有效策略。然而，尚无生物标志物可可靠地预测 AFB 可见的癌前病变患者的肺癌风险。
本研究旨在通过 DNA 拷贝数谱分析确定具有恶性潜能的 AFB 可见的鳞状化生（SqM）病变。
对 474 例肺癌高危人群进行常规 AFB 检查，在基线时发现 6 例患者存在 SqM 病变，在随访支气管镜检查时初始 SqM 部位存在原位癌或癌（原位癌或更高级别）。对这些进行性 SqM 病变的免疫染色模式和基于阵列比较基因组杂交的染色体图谱与 23 例无癌生存患者的 SqM 病变进行比较。确定与癌症风险相关的特定 DNA 拷贝数改变（CNA），并确定该系列中 CNA 预测支气管内癌症的准确性。
在基线时，p53、p63 和 Ki-67 免疫染色对 SqM 病变的不同临床结局无预测作用。病例的基线 SqM 中的平均 CNA 数量明显高于对照组（P < 0.01）。病例 SqM 中改变更频繁的染色体区域为 3p26.3-p11.1、3q26.2-q29、9p13.3-p13.2 和 17p13.3-p11.2（错误发现率 <0.10）。在未来癌症的部位特异性地检测到 CNA。在病例中，基线检测到的 CNA 在前一次活检中持续存在于初始部位，并在癌症进展过程中增加。在该系列中，基于 3p26.3-p11.1、3q26.2-29 和 6p25.3-24.3 的 CNA 建立的模型预测癌症的准确率为 97%。
数据表明，SqM 病变中存在特定的 CNA 可预测支气管内癌症。
