INTRODUCTION

More than 28,000 transplants were performed in 2006 and even more are expected in 2007. As transplant recipients are living longer, the problem of managing their skin cancers becomes more challenging. This is especially true for squamous cell carcinoma (SCC), a significant cause of morbidity and mortality for this group. This chapter will focus on some of the fundamental, molecular mechanisms responsible for accelerated development of SCC in transplant recipients. Chapter 20 will focus on pathogenesis from a more clinical, as opposed to a basic scientific, perspective.

Tumorigenesis is a multistage process where multiple mutations are required to disrupt opposing forces of proliferation, apoptosis, and differentiation and result in the development of a hyperproliferative, invasive clone that does not undergo normal growth arrest. Proliferation and survival are mediated by proto-oncogenes, whereas tumor suppressor genes mediate programmed cell death. There is extensive interplay between genetic and environmental factors that contribute to the development of skin cancer. A simple example might involve an individual with ultraviolet radiation (UVR) overexposure in whom a malignant clone of keratinocytes develops and is allowed to proliferate due to corrupted tumor suppressor mechanisms. Add other potentially carcinogenic factors common in transplant recipients, including the presence of human papillomavirus (HPV) infection, direct proliferative effects attributable to specific immunosuppressive agents, and decreased tumor surveillance, and this represents a patient who is as at high risk for aggressive malignant cutaneous disease. A more detailed explanation of how these factors might interact to accelerate SCC development follows.