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Polycomb group (PcG) genes are responsible for maintenance of cellular identity and contribute to regulation of the cell cycle. Recent studies have identified several PcG genes as oncogenes, and a role for PcG proteins in human oncogenesis is suspected. We investigated the expression of BMI-1 and EZH2 PcG oncogenes in human bronchial squamous cell carcinomas (SCCs) and bronchial premalignant precursor lesions (PLs). Whereas normal bronchial epithelium was associated with widespread expression of BMI-1 in resting EZH2-negative cells, neoplastic cells in lung carcinomas displayed altered expression of both BMI-1 and EZH2. Two patterns of abnormal PcG expression were observed: increased expression of BMI-1 in dividing neoplastic cells of PLs and SCCs, and enhanced expression of EZH2 and Ki-67 in BMI-1-positive cells according to severity of the histopathologic stage. We propose that altered expression of BMI-1 and EZH2 is an early event that precedes high rates of proliferation in lung cancer. Because PcG complexes are normally involved in the maintenance of cell characteristics, abnormal PcG expression may contribute to loss of cell identity.

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Objectives The primary objective of this study was to evaluate the benefit of using a new fluorescence-reflectance imaging system, Onco-LIFE, for the detection and localization of intraepitheal neoplasia and early invasive squamous cell carcinoma. A secondary objective was to evaluate the potential use of quantitative image analysis with this device for objective classification of abnormal sites. Design This study was a prospective, multicenter, comparative, single arm trial. Subjects for this study were aged 45 to 75 years and either current or past smokers of more than 20 pack-years with airflow obstruction, forced expiratory volume in 1 second/forced vital capacity less than 75%, suspected to have lung cancer based on either sputum atypia, abnormal chest roentgenogram/chest computed tomography, or patients with previous curatively treated lung or head and neck cancer within 2 years. Materials and Methods The primary endpoint of the study was to determine the relative sensitivity of white light bronchoscopy (WLB) plus autofluorescence-reflectance bronchoscopy compared with WLB alone. Bronchoscopy with Onco-LIFE was carried out in two stages. The first stage was performed under white light and mucosal lesions were visually classified. Mucosal lesions were classified using the same scheme in the second stage when viewed with Onco-LIFE in the fluorescence-reflectance mode. All regions classified as suspicious for moderate dysplasia or worse were biopsied, plus at least one nonsuspicious region for control. Specimens were evaluated by the site pathologist and then sent to a reference pathologist, each blinded to the endoscopic findings. Positive lesions were defined as those with moderate/severe dysplasia, carcinoma in situ (CIS), or invasive carcinoma. A positive patient was defined as having at least one lesion of moderate/severe dysplasia, CIS, or invasive carcinoma. Onco-LIFE was also used to quantify the fluorescence-reflectance response (based on the proportion of reflected red light to green fluorescence) for each suspected lesion before biopsy. Results There were 115 men and 55 women with median age of 62 years. Seven hundred seventy-six biopsy specimens were included. Seventy-six were classified as positive (moderate dysplasia or worse) by pathology. The relative sensitivity on a per-lesion basis of WLB + FLB versus WLB was 1.50 (95% confidence interval [CI], 1.26–1.89). The relative sensitivity on a per-patient basis was 1.33 (95% CI, 1.13–1.70). The relative sensitivity to detect intraepithelial neoplasia (moderate/severe dysplasia or CIS) was 4.29 (95% CI, 2.00–16.00) and 3.50 (95% CI, 1.63–12.00) on a per-lesion and per-patient basis, respectively. For a quantified fluorescence reflectance response value of more than or equal to 0.40, a sensitivity and specificity of 51% and 80%, respectively, could be achieved for detection of moderate/severe dsyplasia, CIS, and microinvasive cancer. Conclusions Using autofluorescence-reflectance bronchoscopy as an adjunct to WLB with the Onco-LIFE system im...