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Malignant peripheral nerve sheath tumors ( MPNSTs) arising from cranial nerves are rare and usually affect adults. Here we report the clinicopathologic features of a young adult patient with a trigeminal nerve MPNST, in whom another tumor involving the oculomotor nerve on the contralateral side was evident. The patient, an 18-year-old woman, had suffered recurrent paroxysmal sharp stabbing pain over her cheek and forehead on the right side for 1 month. A brain MRI study disclosed a mass, 35 mm in diameter, in the right Meckel's cave, and another mass, 10 mm in diameter, involving the intracranial portion of the left oculomotor nerve. Following gadolinium administration, the former and latter tumors exhibited strong and weak enhancement, respectively. The patient had no clinical stigmata characteristic of neurofibromatosis type 1. Following a tentative diagnosis of schwannoma, total resection of the trigeminal nerve tumor was performed. Histologically, the tumor consisted of highly cellular, spindle-shaped cells arranged in a fascicular pattern, with occasional mitotic figures, nuclear pleomorphism and necrosis. Immunohistochemically, the tumor cells showed variable intensities and frequencies of reactivity for S-100 protein, myelin basic protein, CD34, podoplanin and p53, but no reactivity for Smarcb1. Thus, the tumor exhibited features of MPNST. This case appears to provide information that is useful for accurate diagnosis and surgical planning in patients with bilateral or multiple cranial nerve tumors. [ABSTRACT FROM AUTHOR]

We report two patients with Warthin’s tumor who were also infected with Mycobacterium tuberculosis. Case 1 was a 75-year-old woman with Warthin’s tumor and multiple small epithelioid granulomas with caseous necrosis involving the submandibular gland. This patient died of tuberculous meningitis 4 months after biopsy. Case 2 was a 78-year-old man with a 10-year history of a parotid mass which had enlarged rapidly over 2 months. Surgical excision revealed Warthin’s tumor and epithelioid granulomas involving the left parotid gland. DNA extracted from paraffin sections was amplified by nested polymerase chain reaction (PCR) with primer sets for the mycobacterial 65-KDa antigen gene. Restriction enzyme digestion of the PCR products could differentiate Mycobacterium tuberculosis from other mycobacteria in both cases. Although the histogenesis of lymphoid components of Warthin’s tumor is controversial, the frequent prevalence of inflammation or necrosis and our present findings suggest these components have a similar behavior to regional lymph nodes. [ABSTRACT FROM AUTHOR]

A series of 66 prostate cancer samples were studied immunohistochemically for expression of p53, p21, a cyclin-dependent kinase inhibitor regulated by p53, and cyclin D1, a cell cycle regulatory protein. Twenty samples (30%) showed positive staining for p53, 14 (21%) for p21, and 20 (30%) for cyclin D1. p53 expression was correlated with a high Gleason score while p21 and cyclin D1 did not demonstrate any clear clinicopathological factors. A positive correlation between p53 and p21 expression was observed, however these samples with both positive immunoreactivity had no p53 mutation, suggesting the possibility that p53 may be wild-type and induce p21 expression, and/or p21 is likely to be induced by a p53-independent pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: Neddylation is a process in which the small ubiquitin-like molecule NEDD8 is covalently conjugated to target proteins by sequential enzymatic reactions. Because neddylation plays critical roles in regulating cancer growth and migration, it is emerging as an effective therapeutic target. The major tumor suppressor protein p53 reduces cancer cell migration and is inhibited by neddylation. As p53 is lost or mutated in 50% of various cancer types, this study attempted to investigate how neddylation affects cancer cell migration according to p53 status. Neddylation blockade reduced or caused no change in migration of wild type or mutant p53 cancer cell lines. In contrast, neddylation blockade induced migration of p53-null cancer cell lines. These results were mediated by the differential effect of neddylation blockade on the epithelial–mesenchymal transition activator Slug according to p53 status. Thus, the p53 status of cancer cells should be considered when developing neddylation-targeted anticancer drugs. The tumor suppressor protein p53 is frequently inactivated in human malignancies, in which it is associated with cancer aggressiveness and metastasis. Because p53 is heavily involved in epithelial–mesenchymal transition (EMT), a primary step in cell migration, p53 regulation is important for preventing cancer metastasis. p53 function can be modulated by diverse post-translational modifications including neddylation, a reversible process that conjugates NEDD8 to target proteins and inhibits the transcriptional activity of p53. However, the role of p53 in cancer migration by neddylation has not been fully elucidated. In this study, we reported that neddylation blockade induces cell migration depending on p53 status, specifically via the EMT-promoting transcription factor Slug. In cancer cell lines expressing wild type p53, neddylation blockade increased the transcriptional activity of p53 and expression of its downstream genes p21 and MDM2, eventually promoting proteasomal degradation of Slug. In the absence of p53, neddylation blockade increased cell migration by activating the PI3K/Akt/mTOR/Slug signaling axis. Because mutant p53 was transcriptionally inactivated but maintained the ability to bind to Slug, neddylation blockade did not affect the migration of cells expressing mutant p53. Our findings highlight how the p53 expression status influences neddylation-mediated cell migration in multiple cancer cell lines via Slug. [ABSTRACT FROM AUTHOR]