Practical gastrointestinal oncology correlative science

Gastrointestinal (GI) cancers, like other human malignancies, are characterized by the accumulation of a variety of genetic alterations, including mutations that lead to inactivation of tumor suppressor genes or activation of oncogenes. These genetic and epigenetic changes can be used to classify tumors on the molecular level, and form the basis for development of new prognostic and predictive markers. While a number of molecular prognostic factors in GI cancers have been recognized or postulated (Table 3.1), few have been validated in large data sets to date and their utilization is not yet considered a standard of care. The essential prognostic factors for carcinomas across all GI sites remain the anatomic stage as classified, using TNM categories, lymphovascular invasion, and achievement of margin-negative surgical resection in potentially curable neoplasms. However, with the development of therapies targeted to specific molecular pathways involved in tumorigenesis, characterization of molecular alterations in individual GI malignancies has become important for prediction of response to therapy and thus may be used in some situations to guide selection of treatment options. Currently, the two most prominent examples are colorectal carcinoma and gastrointestinal stromal tumors (GISTs), for which molecular testing for prediction of response to therapy has become widely applied in certain clinical settings, such as KRAS mutational testing prior to treatment with cetuximab in high stage colorectal carcinoma.