Both proteins had been shown to be deregulated in other cancers in a manner that was associated with tumour progression. Recently we reported an association of Microcephalin and ASPM levels in malignant cells derived from ascitic fluids from EOC patients with various clinic-pathological parameters. In the present, larger scale study, nuclear and/or cytoplasmic Microcephalin staining was identified in the tumour cells. Our results in the training set revealed a reduction in nuclear Microcephalin expression in 73% of EOC tumours; this percentage was reduced to 30% in the validation set. This difference between the two cohorts potentially reflects the higher number of grade 3 cases in the training set compared to the validation set. In this study low Microcephalin expression was identified in high grade and advanced stage tumours. These findings match our previous study on ovarian ascites samples that indicated that Microcephalin expression was reduced in cell cultures derived from ascites of EOC patients with advanced tumours. Our results are compatible with studies that reporting reduced MCPH1 DNA copy number in 72% of breast cancers and to our own findings of reduced Microcephalin expression in 93/319 of breast cancer samples, particularly in the higher grade tumours. Previously, we identified a correlation between the abnormal localization of Microcephalin with tumour grade in primary cultures of malignant cells derived from ascitic fluids from patients with EOC. In these cells, cytoplasmic Microcephalin increased with tumour grade. We suggested that might be because of MCPH1 deletion mutations in the C-terminal BRCT domains that have previously been shown to result in Microcephalin moving from a nuclear to cytoplasmic localization similar to BRCA1. A recent study characterizing different MCPH1 splice variants reported mutation or deletion of nuclear localization signals within the MCPH1 gene resulted in a localization change from nuclear to cytoplasmic. In this study weak to moderate Microcephalin cytoplasmic staining was seen in all grade 2 and 3 samples and increased cytoplasmic Microcephalin expression was associated with increased tumour grade. However due to non-specific background cytoplasmic staining observed in the blocking peptide experiment, cytoplasmic expression was not included here. Our findings of reduced expression of the DNA repair protein Microcephalin in high grade tumours but few low grade tumours is consistent with the molecular characteristics of these different tumour types. Loss of DNA repair function e.g. BRCA genes leading to chromosomal instability and a complex genome is common in high grade cancers. In contrast to low grade tumours which do not tend to display chromosomal instability and BRCA mutations. Similarly to Microcephalin expression, in this study we recapitulated our recent findings on cytoplasmic ASPM levels and tumour grade. In primary cultures of malignant cells derived.