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15.07.2016 | Original Article | Ausgabe 4/2016

Virchows Archiv 4/2016

HIF-1α expression and high microvessel density are characteristic features in serrated colorectal cancer

Zeitschrift:
Virchows Archiv > Ausgabe 4/2016
Autoren:
Anne Tuomisto, José García-Solano, Päivi Sirniö, Juha Väyrynen, Miguel Pérez-Guillermo, Markus J Mäkinen, Pablo Conesa-Zamora
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s00428-016-1988-8) contains supplementary material, which is available to authorized users.
Anne Tuomisto and José García-Solano contributed equally to this work

Abstract

Serrated colorectal adenocarcinoma (SAC) is a morphologically distinct subtype of colorectal cancer (CRC), in which increased HIF-1α mRNA expression and HIF-1α protein stabilization are typical features. Here we aimed to further elucidate HIF-1α protein expression in serrated and non-serrated colorectal carcinomas (CRCs) and their precursor lesions and its association with vascular endothelial growth factor (VEGF) and microvascular density (MVD). HIF-1α and VEGF expressions were determined immunohistochemically in 134 serrated polyps (SPs), 104 non-serrated adenomas (NSAs), 81 SACs, and 74 matched conventional adenocarcinomas (CCs) and were correlated with morphology, clinicopathological features, and MVD. In premalignant lesions, both HIF-1α and VEGF were expressed in the vast majority of SPs and NSAs. In CRCs, HIF-1α protein was also present in 77.8 % of SACs, while only 20.3 % of CCs were HIF-1α proficient. MVD was significantly higher in SACs, but the serrated morphology was the only significant predictor of MVD in CRC in multivariate analyses. HIF-1α protein is often stabilized in well-vascularized SACs, suggesting hypoxia-independent stabilization of HIF-1α. Moreover, HIF-1α stabilization did not associate with oncogenic activation of BRAF or KRAS or Von Hippel-Lindau (VHL) mutation. Prevalent HIF-1α expression in SAC and its precursors support the importance of HIF-1α-mediated pathways for the serrated route of colorectal carcinogenesis.

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