The transcription factor grainyhead-like 2 (GRHL2) plays a crucial role in 
various developmental processes. Although GRHL2 recently has attracted 
considerable interest in that it could be identified as a novel suppressor of 
the epithelial-to-mesenchymal transition, evidence is emerging that GRHL2 also 
exhibits tumour-promoting activities. Aim of the present study therefore was to 
help defining the relevance of GRHL2 for human cancers by performing a 
comprehensive immunohistochemical analysis of GRHL2 expression in normal (n = 
608) and (n = 3,143) tumour tissues using tissue microarrays. Consistent with 
its accepted role in epithelial morphogenesis, GRHL2 expression preferentially 
but not exclusively was observed in epithelial cells. Regenerative and 
proliferating epithelial cells with stem cell features showed a strong GRHL2 
expression. Highly complex GRHL2 expression patterns indicative of both reduced 
and elevated GRHL2 expression in tumours, possibly reflecting potential 
tumour-suppressing as well as oncogenic functions of GRHL2 in distinct human 
tumours, were observed. A dysregulation of GRHL2 expression for the first time 
was found in tumours of non-epithelial origin (e.g., astrocytomas, melanomas). 
We also report GRHL2 copy number gains which, however, did not necessarily 
translate into increased GRHL2 expression levels in cancer cells. Results 
obtained by meta-analysis of gene expression microarray data in conjunction with 
functional assays demonstrating a direct regulation of HER3 expression further 
point to a potential therapeutic relevance of GRHL2 in ovarian cancer. 
Hopefully, the results presented in this study may pave the way for a better 
understanding of the yet largely unknown function of GRHL2 in the initiation, 
progression and also therapy of cancers.