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Aims: Cellular expression of heparanase, a degrading enzyme of the extracellular matrix, is associated with poorer prognosis in several cancers. The present analysis, has studied the role of heparanase in tumour growth and clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC)., Methods and Results: We analysed the cellular expression of the active form of heparanase in 71 human HNSCCs, using immunohistochemistry. The results were compared with clinicopathological data and, in 65 cases with immunoreactivity for the proliferation marker, MIB1. Cellular heparanase expression was detected in 41 of 71 (57.74%) cases; in particular, UICC IV-stage tumours showed high heparanase levels. Heparanase was localized mainly in the cytoplasm and, to a lesser extent, at the cell membrane. High levels of heparanase were significantly correlated with an almost four-fold decrease in MIB1 labelling (P = 0.006). Comparison with clinical outcome by multivariate analysis revealed that patients with high-level heparanase expression had prolonged overall survival (P = 0.029)., Conclusions: Although heparanase was mainly found in late-stage HNSCCs, cellular heparanase expression in HNSCCs was associated with prolonged overall survival. We propose that the proliferation-reducing effect of high heparanase levels might outweigh the tumour-promoting effects of heparanase, especially in advanced tumours., (© 2011 Blackwell Publishing Limited.)

Aims: Anorectal melanoma (AM) forms a rare but highly malignant subset of mucosal melanoma with an extremely poor prognosis. Although AMs display histological and immunohistochemical features very similar to cutaneous melanoma (CM), no association exists either with exposure to ultraviolet light or with melanocytic naevi. While AMs are clearly distinguished from CM by displaying few BRAF mutations, they are commonly indistinguishable from CM at the level of gene expression. The aim was to carry out expression analyses of classical immunohistochemical markers and of the protein deleted in malignant brain tumours 1 (DMBT1) in cases of primary anorectal malignant melanoma and CM., Methods and Results: Expression analyses of classical immunohistochemical markers (S100, HMB45, Melan A and MiTF) and of the protein DMBT1 were carried out in 27 cases of primary anorectal malignant melanoma and 26 cases of CM. All AM cases analysed showed expression of at least three of the classical markers for melanoma. However, immunohistochemistry showed 19 out of 27 AM to be positive for DMBT1, which represented a statistically significant difference (P = 0.0009) compared with CM (six out of 26), which more commonly are negative for DMBT1 expression., Conclusion: These results identify DMBT1 as a molecular feature that may allow distinction between AM and CM and support the notion that AM represents an entity molecularly distinct from CM.

Aim: Fatty acid metabolism of the endometrium is important for tissue homeostasis in the proliferative and secretory phase of the menstrual cycle. The enzyme acyl-CoA synthetase 5 (ACS5) plays a crucial role in fatty acid metabolism, mainly through the generation of multifunctional long-chain-fatty-acid-CoA esters. The aim of the present study was to characterize expression and localization of ACS5 in the normal human endometrium and in endometrioid adenocarcinomas., Methods and Results: Expression of ACS5 in the human endometrium was investigated by in situ techniques (immunohistochemistry, mRNA in situ hybridization) and a molecular approach (reverse transcriptase-polymerase chain reaction, Western blot). ACS5 protein and mRNA were localized to the epithelium of the human endometrium. Here, ACS5 expression was found throughout the menstrual cycle as well as in the postmenopausal endometrium. Notably, in endometrioid adenocarcinomas, the ACS5 molecule was found abundantly in well-differentiated tumours, but not in poorly differentiated adenocarcinomas., Conclusions: The abundance of ACS5 in the endometrial epithelium throughout the menstrual cycle provides support for its role in the regulation of tissue homeostasis. With regard to its value for histopathological diagnosis, immunohistochemical characterization of endometrioid adenocarcinomas shows that a decrease in ACS5 expression correlates with tumour dedifferentiation.