Altered Surface Markers in Lung Cancer: Lack of Cell-Surface Fas/APO-1 Expression in Pulmonary Adenocarcinoma May Allow Escape from Immune Surveillanc

Bronchogenic carcinoma is the leading cause of cancer-related mortality, with the prognosis of pulmonary adenocarcinoma remaining poor in advancedstaged tumors despite improved efforts in earlier diagnosis and combination chemotherapy and radiation therapy. Understanding the potential mechanisms underlying the poor survival of these cancers will potentially lead to better therapeutics. One important area that has received significant attention, and with it a greater understanding is the role of apoptosis, or genetically encoded programmed cell death. Apoptosis is defined by distinct characteristic morphological and biochemical changes (1) . In malignant cells, these physiological apoptotic pathways are often altered, resulting in a significant survival advantage for these cells (2) . Tumors with developed resistance to apoptosis can survive despite an active immune system. The Fas receptor (APO-1 or CD95) and its ligand play a key role in the initiation of one apoptotic pathway in malignant tumor (3 -5) . Loss of the Fas protein has been reported to induce resistance to apoptosis, however, apoptotic resistance in some Fas-expressing malignant cells has also been reported (4 ,5) . The Fas receptor is located in the cell surface of tumor cells, and loss of cell-surface Fas protein expression by dislocation of Fas protein is one of the essential mechanisms for tumor immune resistance (6 ,7) . Because of the central roles of FACScan analysis and confocal microscopy in the evaluation of the cell surface Fas protein expression, this chapter focuses on the utilization of these tools in assessment of Fas in lung adenocarcinomas.