Cantu G.,Cranio Maxillo Facial Unit |
Solero C.L.,Fondazione Istituto Neurologico Carlo Besta |
Mariani L.,Clinical Epidemiology and Trial Organization |
Lo Vullo S.,Clinical Epidemiology and Trial Organization |
And 6 more authors.
Head and Neck
Background The purpose of our study was to identify the role of work exposure to organic dusts in patients with malignant paranasal sinus tumors. Methods We analyzed all patients surgically treated for a malignant paranasal sinus tumor at our institution between 1987 and 2006. All patients were specifically asked about their occupational history. The tumor site was classified as maxillary or ethmoid sinus. Adenocarcinomas were divided into intestinal type (ITAC) and non-ITAC. Results The sample included 345 patients with ethmoid sinus and 301 maxillary sinus. Regarding the ethmoid sinus, we found an exposure to organic dusts in 148 of 153 patients with ITAC, in 3 of 16 patients with non-ITAC adenocarcinoma, and in 10 of 176 patients with other tumors. Regarding the maxillary sinus, we found an exposure in 1 of 20 patients with non-ITAC adenocarcinoma and in 4 of 281 patients with other histologies. Conclusion Our study demonstrates that only ethmoid ITACs have an indisputable relationship with the exposure to organic dusts. © 2010 Wiley Periodicals, Inc. Source
Orsenigo M.,Unit of Experimental Molecular Pathology |
Brich S.,Unit of Experimental Molecular Pathology |
Riva C.,Unit of Experimental Molecular Pathology |
Conca E.,Unit of Experimental Molecular Pathology |
And 7 more authors.
Analytical and Quantitative Cytology and Histology
OBJECTIVE: To investigate c-Kit/PDGFRA genomic alterations, KIT-PDGFRA coexpression in gastrointestinal stromal tumors (GISTs) and the role of Bcl-2. STUDY DESIGN: We analyzed 70 primary tumors, 6 recurrences, 4 metastases and 1 recurrence plus metastasis, all molecularly characterized. Alterations in gene copy number were detected by fluorescence in situ hybridization (FISH) and expression of KIT, PDGFRA and Bcl-2 by immunohistochemistry. RESULTS: c-Kit/PDGFRA gene alterations affected 38% of all cases and 39% of primary tumors, with major changes accounting for 15% in both all the cases and primary tumors. Cytoplasmic KIT/PDGFRA coexpression was present in 96.5% of the c-Kit-mutated cases, 100% of the wt c-Kit/PDGFRA cases and 66.6% of the PDGFRA-mutated cases. Bcl-2 immunoreactivity was present in 70% of cases, with expression levels of +++ in 29%, ++ in 38% and + in 33%. CONCLUSION: FISH confirmed cytogenetic alterations in about 40% of primary GISTs at the onset. The high rate of c-Kit/PDGFRA coexpression suggests that both receptors are involved in oncogenicity and may affect imatinib efficacy. The assumption that Bcl-2 expression is supported by the KIT pathway and that its imatinib-mediated down-regulation contributes to autophagic cell death, although attractive, needs to be further confirmed. © Science Printers and Publishers, Inc. Source
Perrone F.,Unit of Experimental Molecular Pathology |
Bossi P.,Unit of Experimental Molecular Pathology |
Cortelazzi B.,Unit of Experimental Molecular Pathology |
Locati L.,Unit of Experimental Molecular Pathology |
And 4 more authors.
Journal of Clinical Oncology
Purpose: To find out if TP53 functional status predicts response to neoadjuvant chemotherapy and thus may be helpful during treatment decision making of oral cavity squamous cell carcinoma (SCC) patients. Patients and Methods: We analyzed the predictive value of TP53 mutations and their functional status on the basis of the transactivation activity of p53 mutant proteins in 53 pretreatment biopsies of oral cavity SCC patients receiving primary cisplatin and fluorouracil chemotherapy followed by surgery. Results: The surgical specimens showed that 15 patients (28%) achieved a pathologic complete remission (pCR) at both T and N sites, and 38 patients had residual tumor cells. Among the 53 pretreatment biopsies, 24 (45%) displayed TP53 mutations: 22 single-nucleotide substitutions and two deletions. According to functional status that could be determined only for the 22 substitutions, 21 mutations were nonfunctional and one was partially functional. TP53 mutation was found in four (27%) of 15 patients who achieved a pCR and in 20 (53%) of 38 nonresponder patients; the difference was not statistically significant (P = .12). In contrast, two (14%) of 14 cases with pCR carried a nonfunctional TP53 mutation, a frequency significantly less than that found in the nonresponders (19 [51%] of 37; P = .02). TP53 mutation predicted pCR in four (17%) of 24 patients and a nonfunctional mutation in only two (9%) of 22 patients. Conclusion: The results indicate that the loss of function (transactivation activities) of p53 mutant proteins may predict a significant low pCR rate and suboptimal response to cisplatin-based neoadjuvant chemotherapy in patients with oral cavity SCC. © 2010 by American Society of Clinical Oncology. Source