Immunochemical analysis of cathepsin B in lung tumours: an independent prognostic factor for squamous cell carcinoma patients

In order to evaluate the possible role of the proteolytic enzyme cathepsin B (cath B)in human non-small cell lung cancer (NSCLC) we examined cath B co ncentrations (cath B-c) and activities (cath B-A) in homogenates of 127 pai rs of lung tumour tissues and corresponding non; tumourous lung parenchyma. Total cath B activity (cath B-AT) and enzymatic activity of the fraction o f cath B, which is stable and active at pH 7.5 (cath B-A7.5) were determine d by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The immun ostaining pattern of cath B was determined in 239 lung tumour tissue sectio ns, showing the presence of the enzyme in tumour cells (cath BT-l) and in t umour-associated histiocytes (cath BH-l). The median levels of cath B-AT, c ath B-A7.5 and cath B-c were 5.6-, 3.2- and 9.1-fold higher (P < 0.001), re spectively, in tumour tissue than in non-tumourous lung parenchyma. Out of 131 tissue sections from patients with squamous cell carcinoma (SCC), 59.5% immunostained positively for cath B, while among the 108 adenocarcinoma(AC ) patients 48.2% of tumours showed a positive reaction. There was a strong relationship between the levels of cath B-AT, cath B-A7.5 cath B-C and cath BT-l, in the primary tumours and the presence of lymph node metastases. Si gnificant correlation with overall survival was observed for cath BT-l, and cath B-A7.5 (P < 0.01 and P < 0.05, respectively) in patients suffering fr om SCC. In these patients positive cath B in tumour cells (cath BT-l) and n egative cath B in histiocytes (cath BH-l) indicated significantly shorter s urvival rate compared with patients with negative cath BT-l and positive ca th BH-l (P < 0.0001). in contrast, in AC patients, both, positive cath BT-l and positive oath BH-l, indicated poor survival probability (P < 0.014). F rom these results we conclude that the proteolytic enzyme cath B is an inde pendent prognostic factor for overall survival of patients suffering from S CC of the lung. (C) 1999 Cancer Research Campaign.