Expression of early lung cancer detection marker p31 in neoplastic and non-neoplastic respiratory epithelium.
In an immunocytochemical study of sputum, two antibodies, including a mouse monoclonal antibody (703D4) to a 31 kDa protein (p31) antigen, have been previously shown to detect lung cancer earlier than routine cytomorphology or chest X-ray. To understand the basis of p31 expression, the distribution of this antigen in the respiratory epithelium of individuals known to have lung cancer was mapped. These individuals are likely to demonstrate extensive changes throughout the epithelium due to field cancerization. p31 immunoreactivity was examined in primary tumors and surrounding non-neoplastic lungs containing both histologically normal and abnormal areas obtained from 28 Stage I non-small cell lung cancer (NSCLC) patients. Distribution and intensity of p31 expression was scored in three lung compartments (bronchi, bronchioli, alveoli). While p31 was present in histologically unremarkable bronchial and bronchiolar epithelium, no expression was detected in bronchi or bronchioli containing histologic abnormalities. Furthermore, in the peripheral lung p31 staining was frequently observed in alveolar type II cells and was most commonly detected in reactive, hyperplastic type II cells. When p31 immunoreactivity was correlated with clinicopathological features, a statistically significant increase in p31 expression was found both in bronchioli and alveoli of older individuals a well as in bronchioli of patients with most extensive smoking exposure. We conclude that p31 expression occurs in both non-neoplastic and neoplastic epithelium of the human respiratory tract. The increased expression of p31 in the peripheral lung may be potentially informative as to what critical cell populations are involved in the development of invasive cancers. Moreover, this study provides a model approach for analysis of the nature of early epithelial changes leading to the development of lung cancer.
Zhou
J
J
Biomarkers and Prevention Research Branch, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
Jensen
S M
SM
Steinberg
S M
SM
Mulshine
J L
JL
Linnoila
R I
RI
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C501479:PSMD8 protein, human; D011506:Proteins; D046988:Proteasome Endopeptidase Complex