José Manuel Aguirre Urízar

Immunoexpression of p53, Ki-67 and E-cadherin in basaloid squamous cell carcinoma of the larynx.

IntroductionBasaloid is a rare and poorly-differentiated variant of squamous cell carcinoma of the larynx, with an invasive solid growth of cells in a lobular configuration. Different molecular markers, such as p53, Ki-67 and E-cadherin, have been shown to be prognostic factors in head and neck cancer.ObjectiveTo evaluate the relationship between the immunoexpression of p53, Ki-67 and E-cadherin in relation to prognosis in basaloid squamous cell carcinoma of the larynx (BSCCL)Patients and methodsWe retrospectively studied 11 cases of BSCCL, all male with a mean age of 62.4 years. Immunohistochemical analyses were performed on paraffin-embedded tissues using p53 (DO-7), Ki-67 (MIB-1) and E-cadherin (56B5) antibodies. Quantitative assessments of the expression and descriptive statistical analyses were performed.ResultsIn 72.7% of the cases, clinically advanced stages III–IV were diagnosed. Average survival time was 56.09 months, and 72.7% of patients died as a consequence of the tumour. Immunoreactivity of p53 (>10% of cells) was detected in the 81.8% of the cases. The 72.7% of the cases showed overexpression of Ki-67 (>50% of cells). The cases with low immunoexpression of Ki-67 and p53 had the best clinicopathological data. All cases showed a decreased expression of E-cadherin.ConclusionsBSCCL is an aggressive variant of the squamous cell carcinoma and has a high expression of p53 and Ki-67 with a low expression of E-cadherin. These results could be related to the aggressiveness of the disease and its poor prognosis.Introduction Basaloid is a rare and poorly-differentiated variant of squamous cell carcinoma of the larynx, with an invasive solid growth of cells in a lobular configuration. Different molecular markers, such as p53, Ki-67 and E-cadherin, have been shown to be prognostic factors in head and neck cancer.

A possible role for fumagillin in cellular damage during host infection by Aspergillus fumigatus

ABSTRACT Virulence mechanisms of the pathogenic fungus Aspergillus fumigatus are multifactorial and depend on the immune state of the host, but little is known about the fungal mechanism that develops during the process of lung invasion. In this study, microarray technology was combined with a histopathology evaluation of infected lungs so that the invasion strategy followed by the fungus could be described. To achieve this, an intranasal mice infection was performed to extract daily fungal samples from the infected lungs over four days post-infection. The pathological study revealed a heavy fungal progression throughout the lung, reaching the blood vessels on the third day after exposure and causing tissue necrosis. One percent of the fungal genome followed a differential expression pattern during this process. Strikingly, most of the genes of the intertwined fumagillin/pseurotin biosynthetic gene cluster were upregulated as were genes encoding lytic enzymes such as lipases, proteases (DppIV, DppV, Asp f 1 or Asp f 5) and chitinase (chiB1) as well as three genes related with pyomelanin biosynthesis process. Furthermore, we demonstrate that fumagillin is produced in an in vitro pneumocyte cell line infection model and that loss of fumagillin synthesis reduces epithelial cell damage. These results suggest that fumagillin contributes to tissue damage during invasive aspergillosis. Therefore, it is probable that A. fumigatus progresses through the lungs via the production of the mycotoxin fumagillin combined with the secretion of lytic enzymes that allow fungal growth, angioinvasion and the disruption of the lung parenchymal structure.