The molecular alterations of pancreatic acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MANECs) are not completely understood, and the possible role of c-MYC amplification in tumor development, progression, and prognosis is not known. We have investigated c-MYC gene amplification in a series of 35 ACCs and 4 MANECs to evaluate its frequency and a possible prognostic role. Gene amplification was investigated using interphasic fluorescence in situ hybridization analysis simultaneously hybridizing c-MYC and the centromere of chromosome 8 probes. Protein expression was immunohistochemically investigated using a specific monoclonal anti-c-myc antibody. Twenty cases had clones with different polysomies of chromosome 8 in absence of c-MYC amplification, and 5 cases had one amplified clone and other clones with chromosome 8 polysomy, while the remaining 14 cases were diploid for chromosome 8 and lacked c-MYC amplification. All MANECs showed c-MYC amplification and/or polysomy which were observed in 54% pure ACCs. Six cases (15.3%) showed nuclear immunoreactivity for c-myc, but only 4/39 cases showed simultaneous c-MYC amplification/polysomy and nuclear protein expression. c-myc immunoreactivity as well as c-MYC amplification and/or chromosome 8 polysomy was not statistically associated with prognosis. Our study demonstrates that a subset of ACCs shows c-MYC alterations including gene amplification and chromosome 8 polysomy. Although they are not associated with a different prognostic signature, the fact that these alterations are present in all MANECs suggests a role in the acinar-neuroendocrine differentiation possibly involved in the pathogenesis of MANECs.

We studied the MSI (microsatellite instability) status and p53 expression in a series of 71 gallbladder cancers (GCs) of different histologic type. All neoplasms were examined combining a microsatellite analysis at mononucleotide locus BAT-26 and an immunohistochemical study for hMSH2, hMLH1, and p53 proteins and markers of gastric and intestinal differentiation. All the 71 GCs were MSS (microsatellite stable). The p53 protein was found in 100% of undifferentiated GCs, 67% of conventional gallbladder adenocarcinomas, 50% of mucinous adenocarcinomas, and 20% GCs with squamous differentiation. All 71 MSS tumors showed presence of immunohistochemical expression of both hMLH1 and hMSH2 gene products. We concluded that microsatellite instability does not play a role in the developing of GC while p53 seems to be the most important alteration found in a large proportion of these cancers, with the only exception of mucinous and squamous gallbladder carcinomas.

Activin A and inhibin A, first isolated from the ovary, are dimeric proteins able to modulate pituitary FSH secretion. Inhibin A is a heterodimer composed of one alpha-subunit and one betaA-subunit (alpha-betaA), while activin A is a homodimer of the betaA-subunit (betaA-betaA). Their identification in several tissues has suggested that they have numerous physiological functions, acting as either paracrine or autocrine factors. The aim of this study was to evaluate the expression of activin A and inhibin A in normal endocrine cells and in 70 endocrine tumours from different sites in the gastro-entero-pancreatic system, using specific monoclonal antibodies directed against the alpha- and betaA-subunits of inhibin/activin. Immunoreactivity for the betaA-subunit, but not for the alpha-subunit, was observed in normal G, EC, and GIP cells of the antrum and duodenum, and in pancreatic A cells. BetaA-subunit expression was observed in G cell and A cell tumours, and in a few insulinomas and ileal EC cell carcinoids. The alpha-subunit was found in rare cells in 7 of the 70 tumours and was colocalized with the betaA-subunit in only 1 tumor. Specific types of endocrine cells from the gut and pancreas appear to produce only activin A, a possible paracrine or autocrine modulator. Activin A is mainly produced by tumours derived from endocrine cells that normally express it.

The occurrence of an epithelial thymoma concomitant with a primary thymic T-cell lymphoblastic lymphoma is rare. This paper describes the case of a patient with a synchronous epithelial thymoma and thymic T-cell lymphoblastic lymphoma, characterized by a rapidly fatal clinical course. A review of the literature is reported.

Despite our preliminary results, the role of pSTAT3 in temporal bone SCC warrants further investigation in larger series because there is increasing evidence in preclinical models to indicate that inhibiting STAT3 phosphorylation can be a useful addition to different anticancer strategies.