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- Title
Differential role of angiogenesis and tumour cell proliferation in brain metastases according to primary tumour type: analysis of 639 cases.
- Authors
Berghoff, Anna S.; Ilhan‐Mutlu, Aysegül; Dinhof, Carina; Magerle, Manuel; Hackl, Monika; Widhalm, Georg; Hainfellner, Johannes A.; Dieckmann, Karin; Pichler, Josef; Hutterer, Markus; Melchardt, Thomas; Bartsch, Rupert; Zielinski, Christoph C.; Birner, Peter; Preusser, Matthias
- Abstract
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.
- Subjects
NEOVASCULARIZATION; METASTASIS; BRAIN diseases; MELANOMA; RENAL cell carcinoma
- Publication
Neuropathology & Applied Neurobiology, 2015, Vol 41, Issue 2, pe41
- ISSN
0305-1846
- Publication type
Article
- DOI
10.1111/nan.12185