Prognostic significance of cortactin levels in head and neck squamous cell carcinoma: comparison with epidermal growth factor receptor status

Cortactin is an actin-binding Src substrate involved in cell motility and invasion. In this study, we sought to examine the prognostic importance of cortactin protein expression in head and neck squamous cell carcinoma (HNSCC). To do so, cortactin and EGF receptor (EGFR) expression was retrospectively evaluated by immunohistochemistry in a tissue microarray composed of 176 HNSCCs with a mean follow-up time of 5 years. Cortactin immunoreactivity was weak to absent in normal epithelial tissue. Overexpression of the protein in 77 out of 176 tumours (44%) was associated with more advanced tumour-node-metastasis stage and higher histologic grade. Cortactin overexpression was associated with significantly increased local recurrence rates (49 vs 28% for high and low expressing carcinomas, respectively), decreased disease-free survival (17 vs 61%), and decreased the 5-year overall survival of (21 vs 58%), independently of the EGFR status. In multivariate analysis, cortactin expression status remained an independent prognostic factor for local recurrence, disease-free survival, and overall survival. Importantly, we identified a subset of patients with cortactin-overexpressing tumours that displayed low EGFR levels and a survival rate that equalled that of patients with tumoral overexpression of both EGFR and cortactin. These findings identify cortactin as a relevant prognostic marker and may have implications for targeted therapies in patients with HNSCC

Fiber Type-Specific Nitric Oxide Protects Oxidative Myofibers against Cachectic Stimuli

Oxidative skeletal muscles are more resistant than glycolytic muscles to cachexia caused by chronic heart failure and other chronic diseases. The molecular mechanism for the protection associated with oxidative phenotype remains elusive. We hypothesized that differences in reactive oxygen species (ROS) and nitric oxide (NO) determine the fiber type susceptibility. Here, we show that intraperitoneal injection of endotoxin (lipopolysaccharide, LPS) in mice resulted in higher level of ROS and greater expression of muscle-specific E3 ubiqitin ligases, muscle atrophy F-box (MAFbx)/atrogin-1 and muscle RING finger-1 (MuRF1), in glycolytic white vastus lateralis muscle than in oxidative soleus muscle. By contrast, NO production, inducible NO synthase (iNos) and antioxidant gene expression were greatly enhanced in oxidative, but not in glycolytic muscles, suggesting that NO mediates protection against muscle wasting. NO donors enhanced iNos and antioxidant gene expression and blocked cytokine/endotoxin-induced MAFbx/atrogin-1 expression in cultured myoblasts and in skeletal muscle in vivo. Our studies reveal a novel protective mechanism in oxidative myofibers mediated by enhanced iNos and antioxidant gene expression and suggest a significant value of enhanced NO signaling as a new therapeutic strategy for cachexia

Usefulness of molecular biology performed with formaldehyde-fixed paraffin embedded tissue for the diagnosis of combined pulmonary invasive mucormycosis and aspergillosis in an immunocompromised patient

Immunocompromised patients who develop invasive filamentous mycotic infections can be efficiently treated if rapid identification of the causative fungus is obtained. We report a case of fatal necrotic pneumonia caused by combined pulmonary invasive mucormycosis and aspergillosis in a 66 year-old renal transplant recipient. Aspergillus was first identified during the course of the disease by cytological examination and culture (A. fumigatus) of bronchoalveolar fluid. Hyphae of Mucorales (Rhizopus microsporus) were subsequently identified by culture of a tissue specimen taken from the left inferior pulmonary lobe, which was surgically resected two days before the patient died. Histological analysis of the lung parenchyma showed the association of two different filamentous mycoses for which the morphological features were evocative of aspergillosis and mucormycosis. However, the definitive identification of the associative infection was made by polymerase chain reaction (PCR) performed on deparaffinized tissue sections using specific primers for aspergillosis and mucormycosis. This case demonstrates that discrepancies between histological, cytological and mycological analyses can occur in cases of combined mycotic infection. In this regard, it shows that PCR on selected paraffin blocks is a very powerful method for making or confirming the association of different filamentous mycoses and that this method should be made available to pathology laboratories

Évaluation de l’imminence de l’accouchement inopiné extra-hospitalier en Guadeloupe : expérience du service médical d’urgence et de réanimation de Pointe-à-Pitre [Assessment of imminence of unplanned out-of-hospital deliveries in Guadeloupe: experience of the mobile emergency and resuscitation service of Pointe-à-Pitre]

National audienceOBJECTIVES: Medical tools to determine the imminence of unplanned out-of-hospital birth have not been validated. The main goal of this study was to analyze assessments of the imminence of these deliveries, by methods such as the Manilas score and the need to push. PATIENTS AND METHODS: All calls made to the Emergency Medical Aid Service in Guadeloupe concerning risks of unplanned delivery between January 1st and June 30th 2011 were reviewed retrospectively, and 69 of the 85 cases cared for by the hospital mobile emergency unit were included. RESULTS: Risks of unplanned out-of-hospital deliveries represented 1.9% of the calls during the study period. The Malinas score was used for dispatching in only 13% and was not used for intervention in any case. It was estimated that the need-to-push feeling was used for 58% (dispatching) and 54.5% (intervention) of patients. Its sensitivity, specificity and predictive values were higher than those of the Malinas score in dispatching and substantially higher in intervention. CONCLUSION: These results argue for the development of tools for estimating the imminence of unplanned delivery. Such tools should be applicable in extra-hospital emergency situations to ensure their use in practice

LANA-1, Bcl-2, Mcl-1 and HIF-1alpha protein expression in HIV-associated Kaposi sarcoma

Human herpesvirus 8 (HHV8) is necessary for Kaposi sarcoma (KS) to develop, but whether the tissue viral load is a marker of KS progression is still unclear. Little is known about the level of expression of apoptosis-regulating proteins and of hypoxia-inducible factors (HIFs) in KS tumour cells relative to HHV8 expression. We therefore investigated the expression of the latency-associated nuclear antigen (LANA-1) of HHV8, Bcl-2, Mcl-1, Bax, Bcl-xL, caspase 3 and HIF-1alphain KS tissue specimens at different stages of the disease. The expression of these proteins was evaluated immunohistochemically using tissue microarrays (TMAs) in tissue specimens from 245 HIV-positive patients at different stages of the disease. Both LANA-1 and HIF-1alpha were expressed in KS biopsies taken at different stages, but their level increased throughout tumour progression. Additionally, the levels of Bcl-2 and Mcl-1 were higher in visceral KS lesions compared to levels observed in cutaneous and mucosal KS. This study demonstrates that late tumour stages of KS in tissues from HIV-positive patients are associated with high levels of LANA-1, HIF-1alpha and of the anti-apoptotic proteins, Bcl-2 and Mcl-1. Finally, the expression of these proteins can be potentially used as a tissue biomarker in defining patients with a higher risk of disease progression

[Basaloid squamous cell carcinomas of the head and neck]

International audienceBasaloid squamous cell carcinomas (SCC) are a rare variant of SCC of the head and neck. Their histological characteristics have been described by Wain in 1986 and are reported in the 2005 WHO classification. A poorer prognosis of BSCC has been reported. Two recent case-control studies have shown a higher rate of distant metastases (15-40%, mean over 30%). Conversely, BSCC have similar or better locoregional control rates, a relatively good radiosensitivity and locoregional control. The role of chemotherapy in the neoadjuvant, concomitant or adjuvant setting needs to be redefined due to high metastatic failure rates; chest CT or PET CT are recommended at baseline and every 6-month during follow-up. Some subgroups of BSCC (oropharynx in particular) are more likely to be associated with oncogenic human papilloma virus HPV16. The determination of BSCC head and neck subgroups by HPV status is critical for the prognosis. The basaloid sub-type of squamous cell carcinomas owing to its particular behavior, should be taken into account while deciding the optimal therapeutic strategy

Morphological analysis of circulating tumour cells in patients undergoing surgery for non-small cell lung carcinoma using the isolation by size of epithelial tumour cell (ISET) method. Cytopathology. Feb.2012 23:30. [PubMed: 21210876

Morphological analysis of circulating tumour cells in patients undergoing surgery for non-small cell lung carcinoma using the isolation by size of epithelial tumour cell (ISET) method Background and objective: Recurrence rates after surgery for non-small cell lung cancer (NSCLC) range from 25 to 50% and 5-year survival is only 60-70%. Because no biomarkers are predictive of recurrence or the onset of metastasis, pathological TNM (pTNM) staging is currently the best prognostic factor. Consequently, the preoperative detection of circulating tumour cells (CTCs) might be useful in tailoring therapy. The aim of this study was to characterize morphologically any circulating non-haematological cells (CNHCs) in patients undergoing surgery for NSCLC using the isolation by size of epithelial tumour cell (ISET) method. Methods: Of 299 blood samples tested, 250 were from patients with resectable NSCLC and 59 from healthy controls. The presence of CNHCs was assessed blindly and independently by 10 cytopathologists on MayGrü nwald-Giemsa stained filters and the cells classified into three groups: (i) malignant cells, (ii) uncertain malignant cells, and (iii) benign cells. We assessed interobserver agreement using Kappa (j) analysis as the measure of agreement. Results: A total of 123 out of 250 (49%) patients showed CNHCs corresponding to malignant, uncertain malignant and benign cells, in 102 ⁄ 250 (41%), 15 ⁄ 250 (6%) and 6 ⁄ 250 (2%) cases, respectively. No CNHCs were detected in the blood of healthy subjects. Interobserver diagnostic variability was absent for CNHCs, low for malignant cells and limited for uncertain malignant and benign cells. Conclusion: Identification of CTCs in resectable NSCLC patients, using ISET technology and according to cytopathological criteria of malignancy, appears to be a new and promising field of cytopathology with potential relevance to lung oncology