ORIGINAL ARTICLE

Biological and prognostic role of acid cysteine proteinase inhibitor (ACPI, cystatin A) in non-small-cell lung cancer

T Leinonen¹, R Pirinen¹, J Böhm¹, R Johansson², A Rinne³, E Weber⁴ and V-M Kosma¹

¹ Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland
² Institute of Clinical Medicine, Oncology, University of Kuopio and Kuopio University Hospital, Kuopio, Finland
³ Proteinase Laboratory, University of Tromsö, Tromsö, Norway
⁴ Institute of Medicine, Department of Physiological Chemistry, Martin-Luther-University of Halle-Wittenberg, Halle, Germany

Correspondence to:
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}uku.fi

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.

Abbreviations: 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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