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Cancer Development


Cancer has a characteristic natural history. Healthy cells first become dysplastic showing subtle morphological abnormalities under the microscope which suggest the beginning of transformation. The next step is carcinoma in situ where characteristic abnormalities of both form and proliferation are present but without invasion of the underlying basement membrane that holds them in place in the tissue of origin. This earliest phase is highly curable and is detected with screening programs, such as the PAP smear for cervical cancer. Localized cancer is stage I disease where the tumor exhibits invasion and disruption of local tissues to form a primary lesion. Tumor cells then invade local lymphatics and spread to the regional (stage II) or extended regional (stage III) draining lymph nodes as secondary tumors. Finally tumor cells invade into the blood stream where characteristic patterns of blood-borne metastasis herald the onset of stage IV disease. Particular tumors vary in the extent to which they follow these phases in sequence: melanoma usually has a distinct loco-regional phase, while breast cancer is systemic from the beginning. Staging correlates with survival and provides an essential guide both to prognosis and to the design of treatment plans.