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

B. Werle, H. Lötterle, U. Schanzenbächer, T. T. Lah, E. Kálmán, K. Kayser, H. Bülzebruck, J. Schirren, M. Krasovec, J. Kos, E. Spiess

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Abstract

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 concentrations (cath B(c)) and activities (cath B(A)) in homogenates of 127 pairs of lung tumour tissues and corresponding non-tumourous lung parenchyma. Total cath B activity (cath B(AT)) and enzymatic activity of the fraction of cath B, which is stable and active at pH 7.5 (cath B(A7.5)) were determined by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The immunostaining pattern of cath B was determined in 239 lung tumour tissue sections, showing the presence of the enzyme in tumour cells (cath B(T-I)) and in tumour-associated histiocytes (cath B(H-I)). The median levels of cath B(AT), cath B(A7.5), and cath B(C) were 5.6-, 3.2- and 9.1-fold higher (P <0.001), respectively, 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 B(T-I) in the primary tumours and the presence of lymph node metastases. Significant correlation with overall survival was observed for cath B(T-I) and cath BA7.5 (P <0.01 and P <0.05, respectively) in patients suffering from SCC. In these patients positive cath B in tumour cells (cath B(T-I)) and negative cath B in histiocytes (cath B(H-I)) indicated significantly shorter survival rate compared with patients with negative cath B(T-I) and positive cath B(H-I) (P <0.0001). In contrast, in AC patients, both, positive cath B(T-I) and positive cath B(H-I), indicated poor survival probability (P <0.014). From these results we conclude that the proteolytic enzyme cath B is an independent prognostic factor for overall survival of patients suffering from SCC of the lung.

Original languageEnglish
Pages (from-to)510-519
Number of pages10
JournalBritish Journal of Cancer
Volume81
Issue number3
DOIs
Publication statusPublished - 1999

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Cathepsin B
Squamous Cell Carcinoma
Lung
Neoplasms
Cathepsin H
Cathepsin C
Histiocytes
Survival

Keywords

  • Cathepsin B
  • Non-small cell lung cancer
  • Prognosis
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Immunochemical analysis of cathepsin B in lung tumours : An independent prognostic factor for squamous cell carcinoma patients. / Werle, B.; Lötterle, H.; Schanzenbächer, U.; Lah, T. T.; Kálmán, E.; Kayser, K.; Bülzebruck, H.; Schirren, J.; Krasovec, M.; Kos, J.; Spiess, E.

In: British Journal of Cancer, Vol. 81, No. 3, 1999, p. 510-519.

Research output: Contribution to journalArticle

Werle, B, Lötterle, H, Schanzenbächer, U, Lah, TT, Kálmán, E, Kayser, K, Bülzebruck, H, Schirren, J, Krasovec, M, Kos, J & Spiess, E 1999, 'Immunochemical analysis of cathepsin B in lung tumours: An independent prognostic factor for squamous cell carcinoma patients', British Journal of Cancer, vol. 81, no. 3, pp. 510-519. https://doi.org/10.1038/sj.bjc.6690723
Werle, B. ; Lötterle, H. ; Schanzenbächer, U. ; Lah, T. T. ; Kálmán, E. ; Kayser, K. ; Bülzebruck, H. ; Schirren, J. ; Krasovec, M. ; Kos, J. ; Spiess, E. / Immunochemical analysis of cathepsin B in lung tumours : An independent prognostic factor for squamous cell carcinoma patients. In: British Journal of Cancer. 1999 ; Vol. 81, No. 3. pp. 510-519.
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T1 - Immunochemical analysis of cathepsin B in lung tumours

T2 - An independent prognostic factor for squamous cell carcinoma patients

AU - Werle, B.

AU - Lötterle, H.

AU - Schanzenbächer, U.

AU - Lah, T. T.

AU - Kálmán, E.

AU - Kayser, K.

AU - Bülzebruck, H.

AU - Schirren, J.

AU - Krasovec, M.

AU - Kos, J.

AU - Spiess, E.

PY - 1999

Y1 - 1999

N2 - 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 concentrations (cath B(c)) and activities (cath B(A)) in homogenates of 127 pairs of lung tumour tissues and corresponding non-tumourous lung parenchyma. Total cath B activity (cath B(AT)) and enzymatic activity of the fraction of cath B, which is stable and active at pH 7.5 (cath B(A7.5)) were determined by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The immunostaining pattern of cath B was determined in 239 lung tumour tissue sections, showing the presence of the enzyme in tumour cells (cath B(T-I)) and in tumour-associated histiocytes (cath B(H-I)). The median levels of cath B(AT), cath B(A7.5), and cath B(C) were 5.6-, 3.2- and 9.1-fold higher (P <0.001), respectively, 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 B(T-I) in the primary tumours and the presence of lymph node metastases. Significant correlation with overall survival was observed for cath B(T-I) and cath BA7.5 (P <0.01 and P <0.05, respectively) in patients suffering from SCC. In these patients positive cath B in tumour cells (cath B(T-I)) and negative cath B in histiocytes (cath B(H-I)) indicated significantly shorter survival rate compared with patients with negative cath B(T-I) and positive cath B(H-I) (P <0.0001). In contrast, in AC patients, both, positive cath B(T-I) and positive cath B(H-I), indicated poor survival probability (P <0.014). From these results we conclude that the proteolytic enzyme cath B is an independent prognostic factor for overall survival of patients suffering from SCC of the lung.

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KW - Non-small cell lung cancer

KW - Prognosis

KW - Squamous cell carcinoma

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