title: Integrin chains beta1 and alphav as prognostic factors in human metastatic melanoma.
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 beta1 and alphav integrin chains for survival of patients with metastatic melanoma. The expression levels of beta1 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 beta1 and alphav integrins in 68 melanoma metastases obtained from 55 patients treated with combined chemoimmunotherapy was studied by immunohistochemistry using anti-beta1 and anti-alphav antibodies. The patients were divided into two groups (using a cut-off point of >/= 81%) for beta1 integrin expression levels and into three categories (negative/low, median, high) for alphav integrin expression levels. All tumours were positive for beta1 integrin, and the tumours (n = 6) which had the highest alphav score were also strongly positive for beta1 (94%; P = 0.0055). Patients (n = 43) with 80% or less beta1 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 beta1 integrin-positive tumour cells had a DFS of only 5.7 months (P = 0.0001). Patients (n = 32) with low alphav 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 alphav expression in their tumours had a median DFS of only 1.8 months (P = 0.0146). Median level expression of beta1 integrin was associated with the presence of Bcl-2 in tumour cells (P = 0.0033). Our results suggest that beta1 and alphav integrin chains are independently expressed in metastatic melanoma and may have an effect on the metastatic potential of melanoma cells.
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland. johanna.nikkola@utu.fi
authors.forename: Johanna
authors.initials: J
authors.lastname: Nikkola
authors.forename: Pia
authors.initials: P
authors.lastname: Vihinen
authors.forename: Tatyana
authors.initials: T
authors.lastname: Vlaykova
authors.forename: Marjo
authors.initials: M
authors.lastname: Hahka-Kemppinen
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heino
authors.forename: Seppo
authors.initials: S
authors.lastname: Pyrhönen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D039564:Integrin alphaV / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015996:Survival Rate; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D039564:Integrin alphaV; D019012:Integrin beta1; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2