Surfactant protein A gene deletion and prognostics for patients with stage I non-small cell lung cancer.
OBJECTIVE
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).


METHODS
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-embedded tissue blocks from 130 patients NSCLC for whom we had follow-up information.


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.
Jiang
Feng
F
Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. fjiang@mail.mdanderson.org
Caraway
Nancy P
NP
Nebiyou Bekele
Benjamin
B
Zhang
Hua-Zhong
HZ
Khanna
Abha
A
Wang
Huijun
H
Li
Ruiyun
R
Fernandez
Ricardo L
RL
Zaidi
Tanweer M
TM
Johnston
Dennis A
DA
Katz
Ruth L
RL
D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics*; D012008:Recurrence; D012907:Smoking; D013997:Time Factors
D014408:Biomarkers, Tumor; D037662:Pulmonary Surfactant-Associated Protein A