Nikkola Johanna, Vihinen Pia, Vlaykova Tatyana, Hahka-Kemppinen Marjo, Heino Jyrki, Pyrhönen Seppo
Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland.
Melanoma Res. 2004 Feb;14(1):29-37. doi: 10.1097/00008390-200402000-00005.
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.
整合素型细胞黏附受体的表达模式在恶性转化过程中常发生改变。在本研究中，我们探讨了β1和αv整合素链对转移性黑色素瘤患者生存的预后意义。还将β1整合素的表达水平与抗凋亡蛋白Bcl-2的表达水平进行了比较，Bcl-2的存在与黑色素瘤的治疗反应和生存相关。使用抗β1和抗αv抗体，通过免疫组织化学研究了从55例接受联合化学免疫治疗的患者中获取的68个黑色素瘤转移灶中β1和αv整合素的表达。根据β1整合素表达水平将患者分为两组（以≥81%为分界点），根据αv整合素表达水平分为三类（阴性/低、中等、高）。所有肿瘤的β1整合素均呈阳性，αv评分最高的肿瘤（n = 6）β1也呈强阳性（94%；P = 0.0055）。样本中β1整合素阳性肿瘤细胞占80%或更少的患者（n = 43）无病生存期（DFS）中位数为17.0个月，β1整合素阳性肿瘤细胞占81%或更多的患者（n = 12）DFS仅为5.7个月（P = 0.0001）。αv整合素表达水平低的患者（n = 32）DFS较短（中位数12.3个月；P = 0.0146），而αv整合素表达水平中等的患者（n = 20）DFS中位数为16.7个月（P = 0.0146）。然而，肿瘤中αv表达非常强的3例患者DFS中位数仅为1.8个月（P = 0.0146）。β1整合素的中等水平表达与肿瘤细胞中Bcl-2的存在相关（P = 0.0033）。我们的结果表明，β1和αv整合素链在转移性黑色素瘤中独立表达，可能对黑色素瘤细胞的转移潜能有影响。
