Duccio Rossi Degl’Innocenti

NF2 gene expression in sporadic meningiomas: Relation to grades or histotypes real time-PCR study

One of the most common regions involved in the meningiomas tumorigenesis is chromosome 22q where the NF2 gene resides. The deficiency or loss of the NF2 gene product, merlin/schwannomin, plays a role in tumor development and metastatization. Conflicting results have been reported on the prognostic value of merlin in meningiomas. Several studies have indicated NF2 gene inactivation as an early tumorigenic event unrelated to the histological grade or clinical behavior. On the contrary, the NF2 gene alteration rate differs between the different histotypes. A pathogenesis independent from the NF2 gene has been suggested in meningothelial meningiomas. In the present work, we studied the NF2 gene expression through real time‐PCR (RT‐PCR) in 30 meningiomas. The average of the NF2 gene expression of all meningiomas was considered as reference value. The average of expression of WHO grade I and II meningiomas was higher than the average of all meningiomas, whereas that of WHO grade III meningiomas was lower. When we compared the NF2 gene expression in the different meningioma grades we did not note a significant difference (P = 0.698) despite the tendency to decrease from grade I to grade III. The average expression of meningothelial meningiomas was higher than the reference value, and that of non‐meningothelial meningiomas was lower. The difference in NF2 gene expression between meningothelial and non‐meningothelial meningiomas was statistically significant (P = 0.013). Our data supports the finding that alterations in NF2 gene alteration are histotype related but not grade related.

Cutaneous pseudolymphoma localized to black tattoo

may also result in extensive scarring and significant delays in diagnosis, biopsy, and treatment of melanoma, which increases the risk of malignancy recurrences from residual cancer cells. Because of the widespread availability of black salve products, physicians need to be familiar with these types of compounds and their potential dangers to educate their patients for their proper use in minor skin problems and the danger of using them for more serious problems.

Hox-D Genes Expression in Pediatric Low-grade Gliomas: Real-time-PCR Study

HOX genes encode transcription factors, which play a key role in morphogenesis and cell differentiation during embryogenesis. Several observations indicate that a deregulated expression of these genes may result in tumor development and progression. Actually, several HOX genes are aberrantly expressed in many tumors and cell lines derived from them. Little is known about the expression of HOX genes in brain tumors. In the present work, we study the relative expression of HOX-D genes (D1, D3, D4, D8, D9, D10, D11, D12, D13) with real-time polymerase chain reaction in a group of 14 pediatric low-grade gliomas. We compare the HOX-D expression level of the 14 tumors with the average expression level of six non-neoplastic human brain tissues. HOX-D1 and HOX-D12 resulted over-expressed in neoplastic samples with respect to non-neoplastic brain parenchyma. Conversely, HOX-D3 was expressed at a lower level in gliomas with respect to non-neoplastic brain. HOX-D4, HOX-D11, and HOX-D13 were never expressed. HOX-D8, HOX-D9, and HOX-D10 were exceptionally expressed in non-neoplastic samples and irregularly expressed in tumors. The observation that all but three HOX-D genes studied are expressed with different pattern in neoplastic and non-neoplastic brain tissue may support the hypothesis that HOX-D genes play a role in the pathogenesis of pediatric low-grade gliomas.

NF2 expression levels of gastrointestinal stromal tumors: a quantitative real-time PCR study

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract. Until today, there have been few markers specific for the tumor. This has complicated the differential diagnosis of the neoplasm from tumors of smooth muscle origin. Recently, the proto-oncogene c-kit has been shown to be a very relevant marker as it almost invariably is expressed in gastrointestinal stromal tumors. Radiation exposure, hormonal and genetic factors, particularly neurofibromatosis 2, have been implicated in their development and growth. GIST initiation, either in NF2-associated or in sporadic cases, is linked to inactivation of members of the proteins 4.1 superfamily. The majority of the mutations identified in the NF2 gene result in a truncated protein and are clinically associated with a severe phenotype. Occasionally, missense mutations associated with a mild phenotype may occur. We compared NF2 gene expression in 5 cases with gastrointestinal stromal tumors by quantitative real-time polymerase chain reaction analysis. NF2 gene mRNA expression was assessed in fresh tissue of stomach from 5 consecutive patients. We detected no alterations in NF2 gene expression in the quantitative analyses of the 5 tumors.

Surveillance for Endometrial Cancer in Women on Tamoxifen: The Role of Liquid-Based Endometrial Cytology – Cytohistological Correlation in a Population of 168 Women

Aims: The aim of this study was to evaluate the utility of liquid-based cytology for endometrial surveillance in patients receiving tamoxifen. Methods: One hundred and sixty-eight women scheduled for hysteroscopy were enrolled in the study. The women sequentially underwent hysteroscopy, endometrial cytology and biopsy. Results: Endometrial biopsy only was inadequate in 112 (67%) patients, both endometrial biopsy and cytology were inadequate in 19 (11%) patients, endometrial cytology only was inadequate in 4 (2%) patients, and both endometrial biopsy and cytology were adequate in 33 (20%) patients. Overall, endometrial biopsy was inadequate in 131 (78%) patients and endometrial cytology in 23 (14%) patients. Endometrial cytology provided sufficient material for diagnosis more often than endometrial biopsy (p < 0.05). In the series of 33 patients (20%) in whom both endometrial cytology and biopsy were adequate, there was a 100% correlation between the endometrial cytology and biopsy results. Conclusions: For the first time, this study shows the diagnostic efficacy of liquid-based endometrial cytology in the follow-up of women receiving tamoxifen. It could be applied solely or in conjunction with ultrasonography.

Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice

It is known that transient receptor potential ankyrin 1 (TRPA1) channels, expressed by nociceptors, contribute to neuropathic pain. Here we show that TRPA1 is also expressed in Schwann cells. We found that in mice with partial sciatic nerve ligation, TRPA1 silencing in nociceptors attenuated mechanical allodynia, without affecting macrophage infiltration and oxidative stress, whereas TRPA1 silencing in Schwann cells reduced both allodynia and neuroinflammation. Activation of Schwann cell TRPA1 evoked NADPH oxidase 1 (NOX1)-dependent H2O2 release, and silencing or blocking Schwann cell NOX1 attenuated nerve injury-induced macrophage infiltration, oxidative stress and allodynia. Furthermore, the NOX2-dependent oxidative burst, produced by macrophages recruited to the perineural space activated the TRPA1–NOX1 pathway in Schwann cells, but not TRPA1 in nociceptors. Schwann cell TRPA1 generates a spatially constrained gradient of oxidative stress, which maintains macrophage infiltration to the injured nerve, and sends paracrine signals to activate TRPA1 of ensheathed nociceptors to sustain mechanical allodynia.Following peripheral nerve injury, influx of immune cells to the site may contribute to the development of chronic pain. Here the authors show that TRPA1 is expressed on Schwann cells and contributes to immune cell influx in a mouse model of neuropathic pain.

MERLIN EXPRESSION IN PEDIATRIC ANAPLASTIC EPENDYMOMAS REAL TIME PCR STUDY

The most common genetic abnormalities of ependymomas involve the chromosome 22 where there is the oncosuppressor gene neurofibromin 2 (NF2). NF2 mutations are primarily encountered in spinal lesions. In contrast, NF2 alterations do not seem related to tumor grade. We studied the NF2 expression through a real-time polymerase chain reaction in 25 pediatric anaplastic ependymomas. We compared the NF2 expression in neoplastic and non-neoplastic tissues, in supratentorial and infratentorial ependymomas and in primitive and non-primitive tumors (recurrences and metastases). Statistical analysis did not prove significant differences. Our results suggest that NF2 alterations are not typical of intracranial anaplastic ependymomas.

Embryonal Tumor: Molecular Characterization

Central Nervous System (CNS) embryonal tumors are malignant neoplasms that share the predilection for the pediatric age, the tendency to early disseminate throughout the CNS via the cerebro spinal fluid, the high mortality and the significant long-term morbidity for survivors.