Soluble and cell-associated transferrin receptor in lung cancer

Abstract

Summary The expression of transferrin receptor (TfR) has been identified in many malignant tumours. In lung cancer, lymphoma and breast cancer, it has been shown that the expression of TfR correlates with tumour differentiation, probably implying some prognostic value. A soluble form of TfR (sTfR) in human serum has been shown to be proportional to the number of cellular TfRs. Based on these data we examined the utility of measuring sTfR in the serum and bronchoalveolar lavage (BAL) fluid of patients with lung cancer (n = 32) and patients with chronic obstructive pulmonary disease (n = 22). BAL fluid was centrifuged to separate the supernatant from the cellular component. Cells were lysed in a detergent and cell-associated TfR was measured by enzyme-linked immunosorbent assay (ELISA) and expressed as ng 106 cells in this cellular component. There was no difference in serum sTfR between the cancer and chronic obstructive pulmonary disease (COPD) groups. A higher level of cell-associated TfR was found in BAL of non-small-cell lung cancer patients than in COPD patients (P = 0.01). The calculated number of TfR molecules per cell in BAL correlated positively with the percentage of macrophages in BAL (P < 0.0001), suggesting that cell-associated TfR in BAL originates primarily from macrophages in this fluid. No correlation existed between BAL cellassociated TfR and tumour size, nodal status, the presence of metastases and serum sTfR. BAL cell-associated TfR was negatively correlated with BAL supernatant neuron-specific enolase (NSE) (P = 0.01). A combination of BAL supernatant NSE and cell-associated TfR detected lung cancer with a sensitivity of 91%, a specificity of 59% and positive and negative predictive values of 81% and 71% respectively. In conclusion, BAL cell-associated TfR may help in the differential diagnosis of lung cancer vs pneumonia.Keywords: lung neoplasm; transferrin receptor; bronchoalveolar lavage Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). Immunohistochemical staining for TfR has been used most extensively for measuring the proliferation rate of cells and is thought to be of some prognostic value in several types of malignant tumours (Faulk et al, 1980;Habelshaw et al, 1983;Wrba et al, 1986). It has also been demonstrated that TfR expression, detected by the monoclonal antibody OKT9, is correlated in pulmonary adenocarcinoma with the degree of histological differentiation, the degree of nuclear atypia and mitotic index and is thus important in prognosis of these malignant tumours (Kondo et al, 1990). A soluble form of TfR (sTfR) in human serum has been shown to be proportional to the number of cellular TfRs (Chitambar et al, 1989). Furthermore, it has recently been demonstrated that bronchoalveolar lavage (BAL) fluid is a suitable place to measure certain markers for lung cancer (De Diego et al, 1991;Dowlati et al, 1996).Based on these preliminary data we investigat...

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