Lung Cancer

1

Is lung cancer a single disease?

Traditionally, lung cancer has been stratified histologically as squamous/epidermoid, adenocarcinoma, and small/large cell lung cancers. Our current ability to profile cancers at the molecular level appears to have both prognostic and therapeutic value.

2

What are the major histologic types of lung cancer?

The most important distinction is between small cell and non–small cell carcinoma because of fundamental differences in tumor biology and clinical behavior ( Table 83.1 ). Patients with small cell lung cancer are classified as having either limited or extensive disease. Limited means that all known disease is confined to one hemithorax and regional lymph nodes, including mediastinal, contralateral hilar, and ipsilateral supraclavicular nodes. Extensive describes disease beyond these limits, including brain, bone marrow, and intraabdominal metastases.

With small cell or neuroendocrine carcinoma, the small cell type is usually extensive at presentation, and 5-year survival is 5%. Neuroendocrine carcinoma, which is well differentiated, is known as atypical carcinoid and has a good prognosis but is not benign.

3

Do genes and heredity play a role in lung cancer?

Yes. A family history of lung cancer probably increases the risk of getting lung cancer. Furthermore, a large array of important biomarkers that influence prognosis have been identified in lung cancer cells and lung cancer tissue.

• Past:

  • Light microscopic evidence of vascular invasion

  • Lymphatic invasion

  • Cellular pleomorphism and mitotic figures

• Present:

  • Proto-oncogenes, growth factors, growth factor receptors

  • Insulin-like growth factor

  • Epidermal growth factor receptor (EGFR)

  • K- ras mutation (cell growth regulation)

  • C- myc overexpression (cell growth)

  • bcl -2 underexpression (loss of apoptosis regulation)

  • Loss of tumor suppressor genes

  • p53

  • Retinoblastoma (RB gene)

  • Chromosomal allele loss

  • Fragile histidine triad gene

  • Retinoic acid receptor a

  • Overactivation of angiogenesis

  • Platelet-derived growth factor

  • Vascular endothelial-derived growth factor

• Future:

  • Gene therapy directed at those listed in present

  • Antiangiogenesis therapy

  • Immunopotentiation

  • Adoptive immunotherapy: Isolation, expansion, and reinfusion of tumor-infiltrating lymphocytes

  • Nonspecific immunostimulation

  • Tumor vaccines

  • No single marker yet has a clear meaning with respect to prognosis in a given patient

4

What risk factors are thought to be important in the development of lung cancer?

• Ninety percent of patients have a smoking history

• Chemicals (aromatic hydrocarbons, vinyl chloride)

• Radiation (radon gas and uranium)

• Asbestos

• Metals (chromium, nickel, lead, and arsenic)

• Environmental factors (air pollution, coal tar, petroleum products)

5

Have culprit genes been identified?

EGFR-activating mutations are associated with increased frequency of stage IV disease and decreased overall survival.