hnRNP B1 expression in benign and malignant lung disease

Abstract

Evidence is accumulating to suggest that hnRNP B1 expression may be a useful tool in the early diagnosis of lung cancer. This study examined the immunohistochemical expression of hnRNP B1 in archived sections of resected lung cancers and compared the patterns of expression with those seen in similar archived sections of non-neoplastic lung. Particular attention was paid to the expression of hnRNP B1 in the benign bronchial cells in both cases, to establish if overexpression of this protein in respiratory epithelial cells is specific for malignancy. Nineteen cases of different types of non-small cell carcinoma were examined (eight squamous cell, six adenocarcinomas, two carcinosarcomas, two undifferentiated large cell carcinomas, and one mucoepidermoid carcinoma) and compared with sections from 16 open lung biopsies (three cases of cryptogenic fibrosing alveolitis, two cases of sarcoidosis, two cases of organizing pneumonia, and one case each of tuberculosis, extrinsic allergic alveolitis, non-specific interstitial pneumonitis, pneumocystis pneumonia, aspergilloma, respiratory bronchiolitis-interstitial lung disease, mineral dust disease, Sjögren's syndrome and systemic sclerosis vascular variant). All the tumours showed positive staining, with the vast majority, 16/19 (84%), showing strong diffuse nuclear staining. The background cells of these cases showed positive staining in alveolar macrophages, lymph node germinal centres, bronchial mucous glands, and bronchial epithelial cells. No significant difference was seen in the percentage of positive bronchial epithelial cells in bronchi adjacent to the tumour compared with the resection margins. In the benign lung cases, positive bronchial epithelial cells were seen in a small percentage, 3/16 (18%), of cases, but the majority of cases showed no or very focal staining. The levels of expression between benign epithelial cells of malignant cases, compared with benign, showed a significant difference when the staining was assessed in percentage of positive nuclei (p = 0.001, Fisher's exact test). The results confirm that hnRNP B1 is widely expressed in a range of lung carcinomas; that expression is seen in benign bronchial epithelial cells and inflammatory cells; and that expression in background bronchial epithelial cells appears to be higher in malignant than in benign lung disease. It is feasible that this biomarker may be of use in the detection of early lung cancer, provided that levels of expression can be accurately quantified.

Deregulated expression of hnRNP A/B proteins in human non-small cell lung cancer: parallel assessment of protein and mRNA levels in paired tumour/non-tumour tissues

“…In other reports, some positive staining of normal cells (albeit of lower intensity than with cancer cells) has been detected with two monoclonal anti-B1 antibodies [23,28,35]. In an exclusive immunohistochemical study using archived tissue sections of resected lung cancers in parallel with control non-cancer tissues from benign lung disease unrelated to cancer, B1 expression was also seen (at a frequency of 25%) in benign bronchial epithelial cells and inflammatory cells of the control group [28]. Nonetheless, hnRNP B1 expression is seen from the early stages of malignant transformation (in occult cancer, bronchial dysplasia and sputum) and is currently considered to be a more specific and sensitive biomarker than hnRNP A2/B1 for the early detection of lung cancer [24,25,27].…”

“…The application of polyclonal antibodies exclusively recognising the hnRNP B1 variant resulted in strong nuclear staining, mainly of squamous cell carcinoma, but not of the normal lung epithelial cells adjacent to tumours [24,27]. In other reports, some positive staining of normal cells (albeit of lower intensity than with cancer cells) has been detected with two monoclonal anti-B1 antibodies [23,28,35]. In an exclusive immunohistochemical study using archived tissue sections of resected lung cancers in parallel with control non-cancer tissues from benign lung disease unrelated to cancer, B1 expression was also seen (at a frequency of 25%) in benign bronchial epithelial cells and inflammatory cells of the control group [28].…”

New biomarkers for lung cancer

“…Finally, Haptoglobin [181], fragment of apolipoprotein A-1 [142] and heterogeneous ribonuclear proteins A2/B1 (hnRNP A2/B1) [182] are also mentioned as lung cancer biomarkers with controversial results.…”

Alternative lengthening of telomeres in the human adrenocortical carcinoma cell line H295R

“…More recently, cyclin D1 overexpression has also been reported to participate in activation of ALT in combination with p53 inactivation in a cancer model using human oral keratinocytes (12). Heterogeneous nuclear ribonucleoproteins (hnRNPs) A2/B1 have reported to be overexpressed in various cancers (13)(14)(15)(16)(17), and also have attracted considerable attention as proteins that bind to single-stranded telomeric DNA (18,19). We previously reported that B1 has stronger affinity for telomeric DNA than A2 and may be an important factor for telomere maintenance (20).…”