Differential role of angiogenesis and tumour cell proliferation in brain metastases according to primary tumour type: analysis of 639 cases
Aim We aimed to characterize angiogenesis and proliferation and their correlation with clinical characteristics in a large brain metastasis (BM) series. Methods Ki67 proliferation index, microvascular density (MVD) and hypoxia‐inducible factor 1 alpha (HIF‐1 alpha) index were determined by immunohis...
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Published in | Neuropathology and applied neurobiology Vol. 41; no. 2; pp. e41 - e55 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Blackwell Publishing Ltd
01.02.2015
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Aim
We aimed to characterize angiogenesis and proliferation and their correlation with clinical characteristics in a large brain metastasis (BM) series.
Methods
Ki67 proliferation index, microvascular density (MVD) and hypoxia‐inducible factor 1 alpha (HIF‐1 alpha) index were determined by immunohistochemistry in BM and primary tumour specimens.
Results
Six hundred thirty‐nine BM specimens of 639 patients with lung cancer (344/639; 53.8%), breast cancer (105/639; 16.4%), melanoma (67/639; 10.5%), renal cell carcinoma (RCC; 52/639; 8.1%) or colorectal cancer (CRC; 71/639; 11.1%) were available. Specimens of the corresponding primary tumour were available in 113/639 (17.7%) cases. Median Ki67 index was highest in CRC BM and lowest in RCC BM (P < 0.001). MVD and HIF‐1 alpha index were both highest in RCC BM and lowest in melanoma BM (P < 0.001). Significantly higher Ki67 indices, MVD and HIF‐1 alpha indices in the BM than in matched primary tumours were observed for breast cancer, non‐small cell lung cancer (NSCLC) and CRC. Correlation of tissue‐based parameters with overall survival in individual tumour types showed a favourable and independent prognostic impact of low Ki67 index [hazard ratio (HR) 1.015; P < 0.001] in NSCLC BM and of low Ki67 index (HR 1.027; P = 0.008) and high angiogenic activity (HR 1.877; P = 0.002) in RCC.
Conclusion
Our data argue for differential pathobiological and clinical relevance of Ki67 index, HIF1‐alpha index and MVD between primary tumour types in BM patients. An independent prognostic impact of tissue‐based characteristics was observed in patients with BM from NSCLC and RCC, supporting the incorporation of these tissue‐based parameters into diagnosis‐specific prognostic scores. |
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Bibliography: | ark:/67375/WNG-PXDC1ZPB-R ArticleID:NAN12185 Medical University of Vienna - No. H-263727/2013 istex:8B7C749114817DC06F17E09B3B636C3516898B0F ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0305-1846 1365-2990 |
DOI: | 10.1111/nan.12185 |