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p16INK4A positivity identifies endometrial surface papillary syncitial change as a regressive feature associated with desquamation

and MAGE-A1 indices in the primary tumour, the respective metastases and local recurrences, suggesting that the percentage of positive tumour cells remains stable throughout the course of the disease (Figure 2D). A significant correlation was observed between the expression of CT antigens and the histological grade of the tumour (GOG) (Spearman’s rank = 0.296, P = 0.009). This depended mainly upon MAGE-A4 expression (Spearman’s rank = 0.20, P = 0.08; v P = 0.04816). We found a significantly good prognosis in the early-stage cases expressing MAGE-A4 compared with those cases without expression (P = 0.04485). MAGE-A1 expression was not prognostic at either stage. In conclusion, this study demonstrates that vSCC frequently expresses cancer ⁄ testis antigens with the exception of NY-ESO-1. MAGE-A4 and MAGE-A1 seem not to detect cancer stem cells because their expression is restricted to squamoid cells, i.e. those showing a certain degree of differentiation at the histological level. MAGE expression may be a transient phenomenon, as it is not present in basaloid cells and is lost in the keratinising cells. This observation further supports the epigenetic determination of MAGE expression. The expression of these antigens is present frequently and constantly throughout the course of the disease and is not correlated with the commonly recognized prognostic factors. The prognostic significance of MAGE-A4 expression in the early stages of the disease suggests that it may represent a tumour suppressor protein and requires further molecular investigation. This novel correlation between MAGE-A4 expression and disease outcome could be pursued by a prospective study in an independent cohort of vSCC. The absence of NY-ESO-1, the presence of reactivity for both MAGE antigens in mature cells with squamous differentiation and the lack of clarity about the role of MAGE-A4 in tumourigenesis imply that these CT antigens are not attractive targets for antigen-specific cancer vaccines in vSCC.