Surfactant Protein A Gene Deletion and Prognostics for Patients with Stage I Non–Small Cell Lung Cancer

Abstract

Purpose: The present study was conducted to determine clinical relevance of surfactant protein A (SP-A) genetic aberrations in early-stage non^small cell lung cancer (NSCLC). Experimental Design: To determine whether SP-A aberrations are lung cancer^specific and indicate smoking-related damage, tricolor fluorescence in situ hybridization with SP-A and PTEN probes was done on touch imprints from the lung tumors obtained prospectively from 28 patients with primary NSCLC. To further define the clinical relevance of SP-A aberrations, fluorescence in situ hybridization was done on both tumor cells and adjacent bronchial tissue cells from paraffin-embeddedtissueblocksfrom130 patientsNSCLC for whomwehadfollow-upinformation. Results: SP-A was deleted from 89% of cancer tissues and the deletion was related to the smoking status of patients (P < 0.001). PTEN was deleted from 16% in the cancer tissues and the deletion was not related to the smoking status of patients (P > 0.05). In the cells isolated from paraffin-embedded tissue blocks, SP-A was deleted from 87% of the carcinoma tissues and 32% of the adjacent normal-appearing bronchial tissues. SP-A deletions in tumors and adjacent normal-appearing bronchial tissues were associated with increases in the risk of disease relapse (P = 0.0035 and P < 0.001, respectively). SP-A deletions in the bronchial epithelium were the strongest prognostic indicators of disease-specific survival (P = 0.025). Conclusions: Deletions of the SP-A gene are specific genomic aberrations in bronchial epithelial cells adjacent to and within NSCLC, and are associated with tumor progression and a history of smoking. SP-A deletions might be a useful biomarker to identify poor prognoses in patients with NSCLC who might therefore benefit from adjuvant treatment.

Automated detection of genetic abnormalities combined with cytology in sputum is a sensitive predictor of lung cancer

“…A bacterial artificial chromosome clone of 180 000 bp, located at 10q22.3 and confirmed to contain genomic sequences of SP-A comprising both SFTPA1 and SFTPA2 (RP11-506MI3; Invitrogen Corp., Carlsbad, CA), was isolated and labeled with Spectrum Green dUTP (Vysis). 5 The chromosomal location of the clone was confirmed on a normal metaphase spread in combination with a centromeric 10 probe, directly fluorescence labeled with Spectrum Orange (Vysis).…”

“…Hybridization and post-washing were carried out as described previously. 5 Counterstaining of nuclei was performed with 4 0 , 6-diamidino-2-phenylindole and evaluated under a fluorescence microscope equipped with the appropriate filter combinations. If the hybridization signals were deemed satisfactory, the slides were sent for automated FISH scanning.…”

“…[5][6][7] These genetic deletions have also been observed in brush specimens of bronchial epithelial cells on the same side as the tumor (TBB), normal lung tissue (NTP) distal to the tumor, and in the main bronchus on the opposite side of the tumor (NBB). 6,7 This 'so-called' molecular field cancerization effect likely results from multiple clonal abnormalities arising within respiratory epithelial cells exposed to carcinogenic substances from tobacco smoke and other pollutants and reflects genetic predisposition for reduced DNA repair capacity in such patients.…”

Surfactant Protein A Suppresses Lung Cancer Progression by Regulating the Polarization of Tumor-Associated Macrophages

“…In addition, a previous study demonstrated that deletion of the SFTPA1 (alias, SPA) gene in nonesmall cell lung cancer cells was associated with tumor progression. 12 Tsutsumida et al 13 found that patients with lung adenocarcinoma with relatively high MUC1 mucin expression and low SP-A expression in cancer cells had a poor outcome. These clinical studies demonstrate that in addition to use as a diagnostic marker, SP-A expression in lung cancer cells could be a useful biomarker of good prognosis.…”

Surfactant Protein-A Concentration in Sera from Dogs with Pulmonary Parenchymal Diseases

“…Therefore, blood SP-A concentration is a useful biomarker for understanding the clinical features of pulmonary diseases and associated prognostic indices [7,19,[24][25][26]. In addition, SP-A can be used as a histopathological marker of pulmonary adenocarcinoma [17], and manifestations of SP-A are associated with lung cancer prognoses [6].…”