The role of apoptosis and expression of bc12 and CD40 in squamous cell carcinoma of the lung

Doctoral thesis English OPEN
Ghosh, Monimoy
  • Subject: RC0254

In spite of extensive research there is little information about apoptosis or programmed cell death in the genesis and progression of cancers of the lung. In our project we have investigated the role of apoptosis and two of the genes controlling apoptosis (bcl2 and C040) in squamous cell carcinoma of the lung. Also we have tried to formulate an accurate way of measuring apoptotic rate in tumour specimens.\ud \ud We counted apoptotic cells in Haematoxylin and Eosin stained histological sections of squamous cell carcinoma of the lung. The apoptotic indices we obtained were very reliable showing remarkable reproducibility and strong correlation with apoptosis measured by monoclonal antibody to apoptosis specific protein (ASP). In our series apoptotic index did not correlate with survival, disease stage, differentiation, AgNOR or DNA ploidy.\ud \ud Histological sections were stained with monoclonal antibodies to Bc12 and CD40. In all, 32% of squamous cell carcinoma of lung were Bc12 positive (i.e. more than 50% of the tumour cells contained Bc12 protein) and 22% were positive for C040. The expression of Bc12 correlated positively with the apoptotic indices. Patients with Bcl2 positive squamous cell lung cancers survived significantly longer although Bcl2 expression did not correlate with any marker of disease severity e.g. stage, grade, AgNOR or DNA ploidy.\ud \ud C040 expression in squamous cell lung cancer had no effect on apoptosis, survival or any of the other previously mentioned markers of disease severity. The expression of C040 in our series showed a tendency to correlate inversely with the expression of Bcl2. \ud \ud We devised a way to measure apoptotie rate in prinwy cultures of tumour cells by serial estimation of sub-diploid fractions in cell suspensions double stained with PI and BerEP4-FITC. We believe that the apoptotic rate measured in this fashion is biologically more relevant, and therefore could be more useful in predicting prognosis, than apoptosis measured from histological sections.
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