Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma

Tjinta Brinkhuizen (Lead / Corresponding author), Chantal A. H. Weijzen, Jonathan Eben, Monique R. Thissen, Ariënne M. van Marion, Björn G. Lohman, Véronique .J L. Winnepenninckx, Patty J. Nelemans, Maurice A. M. van Steensel

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    Abstract

    Background: Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways. Objectives: To determine whether HIF1/mTOR signalling is involved in BCC and TE. Methods: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, 80%). Results: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1α), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. Conclusions: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE.

    Original languageEnglish
    Article numbere106427
    Number of pages10
    JournalPLoS ONE
    Volume9
    Issue number9
    DOIs
    Publication statusPublished - 2 Sep 2014

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    Brinkhuizen, T., Weijzen, C. A. H., Eben, J., Thissen, M. R., van Marion, A. M., Lohman, B. G., Winnepenninckx, V. . J. L., Nelemans, P. J., & van Steensel, M. A. M. (2014). Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma. PLoS ONE, 9(9), [e106427]. https://doi.org/10.1371/journal.pone.0106427