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Differential role of angiogenesis and tumour cell proliferation in brain metastases according to primary tumour type: analysis of 639 cases
Author(s) -
Berghoff Anna S.,
IlhanMutlu 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
Publication year - 2015
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12185
Subject(s) - medicine , angiogenesis , pathology , lung cancer , immunohistochemistry , proliferation index , metastasis , renal cell carcinoma , melanoma , brain metastasis , cancer , hazard ratio , breast cancer , carcinoma , oncology , cancer research , confidence interval
Aim We aimed to characterize angiogenesis and proliferation and their correlation with clinical characteristics in a large brain metastasis ( BM ) series. Methods K i67 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 K i67 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 K i67 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 K i67 index [hazard ratio ( HR ) 1.015; P < 0.001] in NSCLC BM and of low K i67 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 K i67 index, HIF 1‐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.