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Abstract. Salivary gland tumours (SGT) constitute a diagnostically challenging group of neoplasms with frequently unpredictable clinical outcome. The proliferation rate facilitates the identification of aggressive SGT. The Chromatin Assembly Factor-1 (CAF-1) is a major epigenetic regulator of nuclear chromatin organization during DNA replication. It plays a critical function in human tumourigenesis and has been proposed as a new proliferation and prognostic marker for some malignancies. This study focused on the role of CAF-1/p60 protein as a marker of clinical value for SGT. The expression of CAF-1/p60 was evaluated by immunohistochemistry on a retrospective series of 362 surgically excised benign and malignant SGT with different histogenesis and, when available, on fine-needle pre-surgical cytological biopsies. The resulting data were compared with traditional prognostic parameters, including the expression of the routine proliferation marker ki67/MIB1. CAF-1/p60 was detectable in all SGT, with highest degree of expression in metastasizing malignant tumours. Moreover, the cases of benign tumours which progressed to carcinoma during the follow-up, showed significantly higher CAF-1/p60 expression than nonprogressing benign SGT, both on histological sections and cytological smears of the primary tumour. Cox's multiple regression analysis selected CAF-1/p60 expression as the best independent predictor of cancer development for benign SGT (p<0.0001), and the best independent predictor of metastasis onset for malignant tumours (p<0.0004). Overexpression of CAF-1/p60, on histological and/or cytological samples, characterizes malignant SGT with aggressive behaviour, irrespective of their specific histotype, and allows the early diagnosis of progression toward malignancy of morphologically benign tumours.

BackgroundCutaneous melanoma (CM) is the most lethal form of skin malignancy, which registers a constant increase in incidence worldwide. The identification of molecular alteration(s) involved in its biological aggressiveness represents a major challenge for researchers, considering that existing therapies are ineffective to treat metastasizing cases. The epigenetic control of chromatin dynamics during DNA synthesis, replication, and repair is fundamental for the orderly progression of cell proliferation. The Chromatin Assembly Factor 1 (CAF-1) complex acts as a major regulator of this process; its intermediate (p60) subunit has been recently proposed as a novel proliferation and prognostic marker for several tumors. We aimed to establish if the evaluation of the expression of CAF-1/p60 in primary CM may help define the prevision of outcome of patients.MethodsImmunohistochemistry with anti-CAF-1/p60 was performed on paraffin-embedded tissue sections of 130 cases of primary CM retrieved from the archive files of the Department of Biomorphological and Functional Sciences, Section of Pathology, University "Federico II" of Naples, Italy. Results were compared with histopathological and follow-up data of patients.ResultsCAF-1/p60 was expressed in all CM. A significant statistical association between the overexpression of the protein and the occurrence of skin, node and/or distant metastases (P < 0.05) emerged, independently from histopathological prognostic factors.ConclusionsCAF-1/p60 looks promising as a new prognostic marker for CM and sheds new light on the molecular events associated with photocancerogenesis and melanoma biology.The screening for CAF-1/p60 might contribute to the molecular sub-classification of CM, with improved translational outcomes.

Experimental and clinical evidence indicate that immunological mechanisms might be important in the clinical course of uveal malignant melanoma (UMM). We analyzed the amount and phenotype of tumor infiltrating lymphocytes (TIL) and the expression of the apoptosis-inducing molecule Fas and its ligand, FasL, on tumor cells and TIL in a selected series of UMM with the aim to establish if a correlation between their expression and the clinical behavior of UMM exists. TIL phenotype and Fas/FasL expression were evaluated by immunohistochemistry in 61 cases of formalin-fixed, paraffin-embedded UMM. Results were compared with the follow-up data of patients. Most of the UMM showed a prevalence of CD8+ CD3+ T lymphocytes, or CD4+ and CD8+ cells in equal amounts. UMM showed a variable expression of FasL, ranging from 0 to > 40% of neoplastic cells. Fas was always expressed in TIL, although with a variable extent. A subgroup of UMM showed in TIL a strongly reduced or even absent expression ofTCR~-chain, involved in activation ofT-lymphocytes. This subgroup was characterized by a worse outcome. We hypothesized that an impaired cytotoxic immune response due to the loss of the~ chain expression plays a primary role in the biological course of UMM. Our results indicate that the overcoming of the impairment of TCR function may represent a prerequisite for the development of new therapeutic strategies for managing UMM, suggesting that elimination of tumor cells may be possible by activation of cytotoxic cells present within ocular melanomas.Uveal malignant melanoma (UMM) is the most common malignant primary intra-ocular tumor in adults (1-4). It accounts for 70-88% of all ocular tumors, with an annual incidence of approximately 6 cases per milIion per year (1-4). The therapy of UMM is problematic due to the high rate of metastatic dissemination (5). Treatment therapies for this tumor warrant further studies. To date, enucleation remains as effective as the recent eyesparing approaches (6-7). When metastatic disease is diagnosed, patient survival is generally less than 7 months (8-11). During the "dormant" period from diagnosis of primitive tumor and the occurrence of metastasis, chemo-and immunotherapy have also been considered (12).UMM arises in the immune-privileged ocular

High-resolution magic-angle-spinning (HRMAS) one- and two-dimensional (1)H and (13)C NMR spectroscopy was used to study intact healthy (myometrium) and benign (leiomyoma) uterine tissues of 10 patients. Twenty-eight metabolites were detected and assigned in both types of tissue. Principal component analysis (PCA) was applied to a conventional water-suppressed (1)H HRMAS NMR spectrum, and two NMR spectral editing methods, namely Carr-Purcell- Meiboom-Gill (CPMG) spin-echo and diffusion-edited techniques, were used. Only the PCA of CPMG spectra resulted in a good differentiation between the two tissue types. The CPMG spin-echo spectra were also useful in indicating depleted levels of taurine in uterine leiomyomas, which were well correlated with the histopathological determination. In addition, statistical analysis revealed that most leiomyomas contained elevated concentrations of glutamate and glutamine. Our results suggest that HRMAS represents a valuable adjunct to histopathology to improve the diagnostic accuracy of uterine leiomyomas, whilst concomitantly reducing the diagnosis time.