Lung Cancer

Cancer of the lung is the leading cause of death from cancer in all males and in females between the ages of 15 and 64.

Overall, the rate of new cases continues to grow even though the role of cigarette smoke in causing lung cancer is well-established.

Most cancers in the lung are carcinomas - cancers of epithelial cells.

The top pair of images shows the normal epithelium of the bronchi. This photomicrograph is greatly enlarged.

The next three pairs of images show three successive stages of abnormal changes in the bronchial epithelium commonly found in smokers. The drawings show the cellular organization occurring at each stage.

These stages show a well-defined sequence of cellular changes:

• thickening of the epithelium ("hyperplasia")
• loss of the ciliated columnar cells which are
• replaced by a squamous epithelium
• a proliferation of basal cells ("dysplasia") accompanied by
  • development of abnormal cell structure and
  • abnormal nuclei (often aneuploid)

Carcinoma in situ

At later stages, however, the cells have lost the ability to stop dividing; they are now cancerous. But as long as they do not penetrate the basement membrane, they do not metastasize; that is, do not spread in blood and lymph to other parts of the body.

If the lesion is removed at this stage, the patient is cured.

The final pair of images shows the cancerous lesion having broken through the basement membrane (also known as the basal laminar). This is now a full-blown case of lung cancer.

It is the metastasis of these cells to other parts of the body that will kill the patient (most within a year of being diagnosed).

• colon cancer
• cancer of the mouth or pharynx

Genetic analysis reveals that the structural changes seen at each step reflect an accumulation of mutations in

• proto-oncogenes (like RAS or a cyclin gene)
• tumor-suppressor genes (like p53).

Although tumor-suppressor genes are recessive, mutations in one may be accompanied by a loss of the other allele (called loss-of-heterozygosity).

These cells are all members of a clone - the descendants of a single original cell. But as a descendant cell of the clone acquires another mutation, the growth advantage it imparts enables that cell to proliferate and overgrow its less well-endowed cousins.