Abstract 2828: High expression of heat shock protein 27 in metastases is correlated with response to bevacizumab monotherapy in patients with metastatic melanoma
Authors: Schuster Cornelia , Akslen Lars A. , Straume Oddbjørn 
Published: May 2015

Abstract
Background: Angiogenesis is a hallmark of cancer and essential for tumor growth and metastases. It is known that melanomas are often highly vascularized. The main objective of this study was to identify predictive markers of anti-angiogenic treatment in patients with metastatic melanoma who were treated with bevacizumab monotherapy in a phase II clinical trial. As previously published, this treatment is well tolerated and showed disease control (CR, PR and SD for at least 6 months) in 31% of the patients. Lactate dehydrogenase, M-stage and early hypertension are predictive markers.
Methods: 35 patients were enrolled in an open-label single arm phase II clinical trial at Haukeland University Hospital, Norway, and were treated with bevacizumab 10mg/kg q14 until disease progression or intolerable toxicity (ClinicalTrials.gov: NCT00139360). Paraffin embedded tissue of primary tumors and metastases as well as blood samples were available for investigation. Tissue sections (5µm) were stained with primary antibodies for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and heat shock protein 27 (HSP27). A staining index (SI) was used to quantify expression in primary tumors and metastases, as the product of staining intensity (0: absent, 1: weak: 2: moderate, 3: strong) and area (0: no positive tumor cells, 1: &lt;10% positive tumor cells, 2: 10-50% positive tumor cells, 3: &gt; 50% positive tumor cells). In addition, enzyme linked immune assay (ELISA) was performed for VEGF165 in plasma samples as well as bFGF and HSP27 in serum samples.
Results: 100% of the patients with high cytoplasmic HSP27 expression in metastases had either complete remission or partial response. Conversely, none of those with low HSP27 SI responded to treatment with bevacizumab monotherapy (Mann-Whitney U-test, p=0.044). All patients with high SI in primary tumors showed a non-significant trend to better treatment response. In contrast, there was no association between cytoplasmic VEGF staining index in primary tumors or metastases and response. Neither cytoplasmic nor nuclear staining for bFGF in primary tumors or metastases could predict response to treatment. Measurements of HSP27 and bFGF in serum and VEGF165 in plasma did not show any correlation to treatment response.
Conclusion: High staining index of HSP27 in metastases is significantly associated with response to treatment with bevacizumab monotherapy in patients with metastatic melanoma.
Citation Format: Cornelia Schuster, Lars A. Akslen, Oddbjørn Straume. High expression of heat shock protein 27 in metastases is correlated with response to bevacizumab monotherapy in patients with metastatic melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2828. doi:10.1158/1538-7445.AM2014-2828