DNA copy number alterations in squamous metaplastic lesions predict lung cancer

No biomarker can reliably predict cancer risk in individual subjects who present with AFB-visualized premalignant lesions. Our present study was set out to identify AFB-visualized squamous metaplastic (SqM) lesions with malignant potential by DNA copy number profiling. Within our cohort of 474 subjects at risk of lung cancer who underwent regular AFB examinations, 6 (1.3%) subjects showed rapid progression from SqM to carcinoma ( in situ ) (cases). P53, p63 and Ki-67 immunostaining patterns and arrayCGH-based DNA copy number profiles of progressive SqM lesions (n=6) were compared to those of a subset of SqM lesions of subjects who remained cancer-free (controls; n=23). Specific DNA copy number alterations (CNAs) linked to cancer risk were identified and accuracy to predict cancer in this series was determined. While clinicopathologic characteristics and immunostaining patterns were not related to clinical outcome of SqM, the mean number of CNAs in SqM of cases (22%, range 0.48-39%) was significantly higher as compared to controls (0.09%, range 0-1.32%, p Our data strongly suggest that CNAs predict endobronchial cancer in individual subjects diagnosed with AFB-visualized SqM, and may be used to guide intervention to prevent lung cancer.