Later, we shall see that there is also a different way to classify cancers, one that cuts across the traditional classification by site of origin: we can classify them in terms of the mutations that make the tumor cells cancerous. The final section of the chapter will show how this information can be crucial to the design and choice of treatments.
Figure 20–1 Metastasis. Malignant tumors typically give rise to metastases, making the cancer hard to eradicate. Shown in this fusion image is a whole-body scan of a patient with metastatic non-hodgkin’s lymphoma (NhL). The background image of the body’s tissues was obtained by CT (computed x-ray tomography) scanning. Overlaid on this image, a PET (positron emission tomography) scan reveals the tumor tissue (yellow), detected by its unusually high uptake of radioactively labeled fluorodeoxyglucose (FDG). high FDG uptake occurs in cells with unusually active glucose uptake and metabolism, which is a characteristic of cancer cells (see Figure 20–12). The yellow spots in the abdominal region reveal multiple metastases. (Courtesy of S. Gambhir.) respiratorycancers of system epithelia: carcinomas breast blood: myelomas, leukemias, and lymphomas bones, connective tissue, new cases muscles, and vasculature
KEY: deaths/year endocrine system, thyroid
Even when a cancer has metastasized, we can usually trace its origins to a single primary tumor, arising in a specific organ. The primary tumor is thought to derive by cell division from a single cell that initially experienced some heritable change. Subsequently, additional changes accumulate in some of the descendants of this cell, allowing them to outgrow, out-divide, and often outlive their neighbors. By the time it is first detected, a typical human cancer will have been developing for many years and will already contain a billion cancer cells or more (Figure 20–4). Tumors will usually also contain a variety of other cell types; for example, fibroblasts will be present in the supporting connective tissue associated with a carcinoma, in addition to inflammatory and vascular endothelial cells. How can we be sure that the cancer cells are the clonal descendants of a single abnormal cell?
One way of proving clonal origin is through molecular analysis of the chromosomes in tumor cells. In almost all patients with chronic myelogenous leukemia (CML), for example, we can distinguish the leukemic white blood cells from the patient’s normal cells by a specific chromosomal abnormality: the so-called Philadelphia chromosome, created by a translocation between the long arms of chromosomes 9 and 22 (Figure 20–5). When the DNA at the site of translocation is cloned and sequenced, it is found that the site of breakage and rejoining of the translocated fragments is identical in all the leukemic cells in any given patient, but that this site differs slightly (by a few hundred or thousand base pairs) from one patient to another. This is the expected result if, and only if, the cancer in each patient arises from a unique accident occurring in a single cell. We will see later
Figure 20–2 Cancer incidence and mortality in the United States. The total number of new cases diagnosed in 2012 in the United States was 1,665,540, and total cancer deaths were 585,720. Note that deaths reflect cases diagnosed at many different times and that somewhat less than half of the people who develop cancer die of it. In the world as a whole, the five most common cancers are those of the lung, stomach, breast, colon/rectum, and uterine cervix (included in the figure under the heading of reproductive tract), and the total number of new cancer cases recorded per year is just over 6 million. Skin cancers other than melanomas are not included in these figures, since almost all are cured easily and many are unrecorded.