Ductal adenocarcinoma of the pancreas is ranking 4 for patient' death from malignant disease in Western countries, with no satisfactory treatment. We re-examined more precisely the histone deacetylases (HDAC) and Sirtuin (SIRT) gene expression patterns in pancreatic cancer with more pancreatic tumors and normal tissues. We also examinedthe possible relationship between HDAC gene expression levels and long term disease outcome. Moreover, we have evaluated by using an in vitro model system of human pancreatic tumor cell line whether HDAC7 knockdown may affect the cell behavior. We analyzed 29 pancreatic adenocarcinoma (PA), 9 chronic pancreatitis (CP), 8 benign pancreatic (BP) and 11 normal pancreatic tissues. Concerning pancreatic adenocarcinoma, we were able to collect biopsies at the tumor periphery. To assess the possible involvement of HDAC7 in cell proliferation capacity, we have generated recombinant human Panc-1 tumor which underexpressed or overexpressed HDAC7. The expression of HDAC1,2,3,4,7 and Nur77 increased in PA samples at levels significantly higher than those observed in the CP group (p = 0.0160; 0.0114; 0.0227; 0.0440; 0.0136; 0.0004, respectively). The expression of HDAC7, was significantly greater in the PA compared with BP tissue samples (p = 0.05). Mean mRNA transcription levels of PA for HDAC7 and HDAC2 were higher when compared to their counterpart biopsies taken at the tumor periphery (p = 0.0346, 0.0053, respectively). Moreover, the data obtained using confocal microscopy and a quantitative method of immunofluorescence staining strongly support the HDAC7 overexpression in PA surgical specimens. The number of deaths and recurrences at the end of follow up were significantly greater in patients with overexpression of HDAC7. Interestingly, the rate of growth was significantly reduced in the case of cell carrying shRNA construct targeting HDAC7 encoding gene when compared to the parental Panc-1 tumor cells (p = 0.0015) at 48 h and 96 h (p = 0.0021). This study strongly support the notion that HDAC7play a role in pancreatic adenocarcinoma progression.

Purpose: To evaluate the impact of tonsillectomy on the detection of the primary tumor, based on p16 immunohistochemistry analysis, in patients with cervical unknown primary of squamous cell carcinoma (SCC-CUP). Methods: This was a retrospective study of 63 patients, included from January 2008 to December 2017 in a single institution. All patients had an initial assessment with physical examination, CT scan of the neck and chest, whole body FDG-PET CT, and endoscopy under general anesthesia, which failed to determine the primary tumor. Results: Forty-seven out of the 63 patients had an ipsi-or bilateral tonsillectomy which revealed 12 tonsil cancers (26%). The tonsil primary was ipsilateral to positive nodes in 10 cases, contralateral in 1 case and, in 1 case, the patient had bilateral neck involvement. The analysis of the p16 status was carried out in 41/63 patients (65%). Among the 32 patients who had a p16 analysis and tonsillectomy, the rate of primary detection was 59% (10/17) for p16-postives and 0% (0/15) for p16-negatives (p < 0.001). Conclusion: These results suggest that an extended work-up should be systematically proposed including bilateral tonsillectomy (+/-mucosectomy of the base of tongue) in SCC-CUP p16-positive patients but not in p16-negatives.

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