5: Neoplasia

Introduction

Cell growth and maturation are normal events in organ development during embryogenesis, growth, and tissue repair and remodeling after injury. Disordered regulation of these processes can result in loss of control over cell growth, differentiation, and spatial confinement. Human neoplasia collectively represents a spectrum of diseases characterized by abnormal growth of cells resulting in distorted tissue architecture. Although cancers are typically classified by their tissues of origin or anatomic location, many features are shared by all types. There is also considerable variation among patients with a given type of cancer in the nature of cellular alterations as well as the clinical presentation and course of disease. The recognition of overt malignancy by physical examination or imaging requires the presence in the body of about 1 billion malignant cells. A preclinical phase may sometimes be recognized. Preclinical signs may consist of, among others, polyps in the colon or dysplastic nevi on the skin—potential precursors of colon carcinoma and malignant melanoma, respectively. Such precursor lesions usually harbor molecular genetic abnormalities and exhibit features of abnormal cell proliferation without the demonstration of invasiveness and may precede the development of an invasive malignancy by months to years, or may not progress to cancer within the individual’s lifetime. More commonly, the preclinical phase goes undetected until invasive cancer, occasionally with regional or distant metastases, is already present. As is the case with other medical disorders, our understanding of the pathophysiology of neoplasia has been based on clinical and pathologic observations of large series of patients. More recently, cellular and molecular features of cancer cells have been described, and their relationships to certain neoplastic entities and clinical situations have extended our knowledge in this field.

The Molecular & Biochemical Basis of Neoplasia

The process of neoplasia is a result of stepwise alterations in cellular function. These phenotypic changes confer proliferative, invasive, and metastatic potential that are the hallmarks of cancer. It is generally believed—although not conclusively proved—that genetic alterations underlie all cellular and biochemical aberrations responsible for the malignant phenotype. In addition to mutational changes that alter the genetic code, epigenetic changes also underlie cellular and biochemical aberrations that contribute to the malignant phenotype. Epigenetic phenomena influence gene expression and cell behavior, and although once acquired they are transmitted to daughter cells with cell division, they are not changes in the genetic code. An example of this is the silencing of certain genes by hypermethylation of DNA in the promoter region. An increasing number of genetic and cellular changes are being catalogued from the study of cancer cells, both in vivo, from primary tumors of patients, and in vitro, from established cancer cell lines grown in tissue culture. Some alterations are related to particular cellular phenotypes, such as a high proliferative rate or metastatic ...