Integrin chains β1 and αv as prognostic factors in human... : Melanoma Research (original) (raw)

ORIGINAL ARTICLES

Nikkola, Johannaa d; Vihinen, Piaa d; Vlaykova, Tatyanaa; Hahka-Kemppinen, Marjob; Heino, Jyrkic d; Pyrhönen, Seppoa d

aDepartment of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland

bOy Eli Lilly Finland Ab, Vantaa, Finland

cDepartment of Environmental Sciences, University of Jyväskylä, Jyväskylä, Finland

dMediCity Research Laboratory, University of Turku, Turku, Finland

Sponsorship: This work was supported by a grant from the Finnish Cancer Foundation, the Finnish Cultural Foundation, Turku University Foundation and South-West Funds of Cancer Foundation

Correspondence and requests for reprints to J. Nikkola, MediCity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Tel: (+358) 2 333 7001; fax: (+358) 2 333 7000;

e-mail: [email protected]

Received 18 June 2003 Accepted 20 October 2003

Abstract

The expression pattern of integrin-type cell adhesion receptors is often changed during malignant transformation. In the present work, we studied the prognostic significance of β1 and αv integrin chains for survival of patients with metastatic melanoma. The expression levels of β1 integrin were also compared with those of Bcl-2, an anti-apoptotic protein, the presence of which is associated with treatment response and survival in melanoma. The expression of β1 and αv integrins in 68 melanoma metastases obtained from 55 patients treated with combined chemoimmunotherapy was studied by immunohistochemistry using anti-β1 and anti-αv antibodies. The patients were divided into two groups (using a cut-off point of ≥81%) for β1 integrin expression levels and into three categories (negative/low, median, high) for αv integrin expression levels. All tumours were positive for β1 integrin, and the tumours (n = 6) which had the highest αv score were also strongly positive for β1 (94%; P = 0.0055). Patients (n = 43) with 80% or less β1 integrin-positive tumour cells in their samples had a median disease-free survival (DFS) of 17.0 months, and patients (n = 12) with 81% or more β1 integrin-positive tumour cells had a DFS of only 5.7 months (P = 0.0001). Patients (n = 32) with low αv integrin expression levels had shorter DFS (median 12.3 months; P = 0.0146) than patients (n = 20) with median expression levels (median 16.7 months; P = 0.0146). However, three patients who had a very strong αv expression in their tumours had a median DFS of only 1.8 months (P = 0.0146). Median level expression of β1 integrin was associated with the presence of Bcl-2 in tumour cells (P = 0.0033). Our results suggest that β1 and αv integrin chains are independently expressed in metastatic melanoma and may have an effect on the metastatic potential of melanoma cells.