Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI). Because cancers with MSI account for approximately 15% of all colorectal cancers and because of the need for a better understanding of the clinical and histologic manifestations of HNPCC, the National Cancer Institute hosted an international workshop on HNPCC in 1996, which led to the development of the Bethesda Guidelines for the identification of individuals with HNPCC who should be tested for MSI. To consider revision and improvement of the Bethesda Guidelines, another HNPCC workshop was held at the National Cancer Institute in Bethesda, MD, in 2002. In this commentary, we summarize the Workshop presentations on HNPCC and MSI testing; present the issues relating to the performance, sensitivity, and specificity of the Bethesda Guidelines; outline the revised Bethesda Guidelines for identifying individuals at risk for HNPCC; and recommend criteria for MSI testing.

Early detection represents one of the most promising approaches to reducing the growing cancer burden. It already has a key role in the management of cervical and breast cancer, and is likely to become more important in the control of colorectal, prostate and lung cancer. Early-detection research has recently been revitalized by the advent of novel molecular technologies that can identify cellular changes at the level of the genome or proteome, but how can we harness these new technologies to develop effective and practical screening tests?

PC is equally efficacious as VC for the treatment of advanced non--small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.