Molecular biologic staging of esophageal cancer.
The molecular biology of esophageal cancer is characterized by a series of genetic mutations that occur throughout the progression from normal squamous epithelium to carcinoma. The most important risk factor for the development of adenocarcinoma, which is increasing in incidence, is the presence of CLE. The pathophysiology of CLE appears to be related to duodenogastroesophageal reflux, also increasing in incidence. The genetic mutations that are responsible for tumorigenesis have been described, although the precise sequence of mutations is variable. Analysis of molecular biologic factors that are important in tumorigenesis may be used in clinical applications: establishing diagnosis, assessing prognosis, and assigning therapy. The development of molecular biologic substaging of patients with CLE may potentially identify patients with elevated malignant potential and expedite therapy. The ability of molecular markers to predict resistance to chemotherapy and radiation therapy represents an important potential advantage, with two possible applications. Predictable resistance to a particular chemotherapeutic agent would allow the selection of a alternative agent, with a greater potential for efficacy. Furthermore, known mechanisms of resistance, which have been analyzed using molecular markers, may be inhibited or reversed. The molecular biology of esophageal cancer requires further study. The molecular events and factors that are involved may be important in the diagnosis, staging, and treatment of esophageal cancer, in addition to the description of tumorigenesis.
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