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Biological and prognostic role of acid cysteine proteinase inhibitor (ACPI, cystatin A) in non-small-cell lung cancer
  1. T Leinonen1,
  2. R Pirinen1,
  3. J Böhm1,
  4. R Johansson2,
  5. A Rinne3,
  6. E Weber4,
  7. V-M Kosma1
  1. 1Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland
  2. 2Institute of Clinical Medicine, Oncology, University of Kuopio and Kuopio University Hospital, Kuopio, Finland
  3. 3Proteinase Laboratory, University of Tromsö, Tromsö, Norway
  4. 4Institute of Medicine, Department of Physiological Chemistry, Martin-Luther-University of Halle-Wittenberg, Halle, Germany
  1. Correspondence to:
 Dr V-M Kosma
 Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland; velimatti.kosma{at}


Background: Acid cysteine protease inhibitor (ACPI) is an intracellular protein, often linked to neoplastic changes in epithelium and thought to have an inhibitory role in malignant transformation.

Aim: To analyse the expression and prognostic role of ACPI in non-small-cell lung cancer (NSCLC).

Method: Histological samples from 199 patients with resected NSCLC were stained immunohistochemically for the expression of ACPI in normal and preneoplastic bronchial epithelium, and in various types of lung carcinomas.

Results: A normal bronchial epithelium showed positive staining for ACPI in the basal cells, whereas the upper two-thirds of the dysplastic epithelium was ACPI positive. High staining for ACPI was found in 74% (91/123) of squamous-cell carcinomas, whereas 16% (8/49) of adenocarcinomas and 30% of (8/27) large-cell carcinomas showed the high expression of ACPI (p<0.001). Among squamous-cell carcinomas, low expression of ACPI was correlated with poor tumour differentiation (p = 0.032). In the whole tissue, reduced expression of ACPI was associated with tumour recurrence (p = 0.024). In overall survival (OS) and disease-free survival (DFS) analyses, the histological type of the tumour (both p<0.001) and stage of the tumour (p = 0.001, p = 0.013, respectively) were related to patient outcome. Low expression of ACPI in tumour cells was associated with poor OS and DFS (p<0.041, p = 0.004, respectively). In multivariate analysis, ACPI did not retain its prognostic value, whereas the traditional factors were the most important prognostic factors.

Conclusions: ACPI expression is linked with the malignant transformation of the bronchial epithelium and predicts a risk of tumour recurrence as well as poor rate of survival for the patients. However, ACPI does not have any independent prognostic value in NSCLC.

  • ACPI, acid cysteine protease inhibitor
  • OS, overall survival
  • DSF, disease-free survival
  • PBS, phosphate buffer solution
  • NSCLC, non-small-cell lung cancer

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  • Published Online First 21 June 2006

  • Competing interests: None.