Skin cancer, the most common cancer in the U.S., is more prevalent than all other malignancies combined. Basal cell carcinoma (BCC), the most common form of human cancer, shows evidence for spontaneous regression in approximately 44% of the tumors. Importantly, both spontaneous regression of tumors and appearance of new tumors appear to be related to the immune response to the tumor. Focusing on the microenvironment within BCC tumors, this study addresses the interplay between psychological factors and immune function, and how this interplay may be related to immune/molecular markers associated with histopathological characteristics of BCC tumors that are relatively higher or lower in their immunoreactivity. We will recruit 320 patients who have recently had a BCC removed (the """"""""index"""""""" tumor). Two pathologists will evaluate the tumors and assess their immunoreactivity as measured by the level of immune cells trafficking to the tumor and the expression of immune and apoptotic markers expressed by these cells; they will also determine the tumor subtype. We will evaluate cross-sectional relationships between the immunogenic status of the BCC tumors and the influence of age, gender, severe life stressors, and depressive symptoms. Accordingly, we have the following specific aims: 1) Using the index BCC, we will determine if depressive symptoms and severe life stressors are related to markers shown to be reflective of immunoreactivity to a BCC, i.e., tumors showing differences in the level of CD3+ and CD68+ cells that traffic to the BCC tumor and surrounding stroma (quantitative measures) and the expression of cell markers, including CD25, ICAM-1, IFN-gamma, and IL-10, reflecting the activation of these cells (qualitative measures) and bcl-2, an apoptosis marker associated with tumor regression. 2) We will determine if the relationships between depressive symptoms and severe life stressors and tumor immunoreactivity are more pronounced among older adults.
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