lunes, 4 de febrero de 2019

Cancer Pathophysiology

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By Ananya Mandal, MDReviewed by April Cashin-Garbutt, MA (Cantab)

Cancer has a complex Pathophysiology. Pathologists are physicians who are concerned primarily with the study of disease in all its aspects. This includes cause of the disease, diagnosis, how the disease develops (pathogenesis), mechanism and natural course of the disease. They also deal with biochemical features, progression, and prognosis or outcome of the disease.

Pathology of cancers and other complex disorders have undergone a sea change after development of technologies like immunohistochemistry, flow cytometry, and molecular biologic approaches to cancer diagnosis.

Genetic changes

In normal cells, genes regulate growth, maturity and death of the cells. Genetic changes can occur at many levels. There could be a gain or loss of entire chromosomes or a single point mutation affecting a single DNA nucleotide.

There are two broad categories of genes which are affected by these change:

Oncogenes – these are cancer causing genes. They may be normal genes which are expressed at inappropriately high levels in patients with cancers or they may be altered or changed normal genes due to mutation. In both cases these genes lead to cancerous changes in the tissues.
Tumor suppressor genes – these genes normally inhibit cell division and prevent survival of cells that have damaged DNA. In patients with cancer these tumor suppressor genes are often disabled. This is caused by cancer-promoting genetic changes. Typically, changes in many genes are required to transform a normal cell into a cancer cell.

Genomic amplification

Sometimes there may be genomic amplification. Here a cell gains many copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material.

Point mutations

Point mutations occur at single nucleotides. There may be deletions, and insertions especially at the promoter region of the gene. This changes the protein coded for by the particular gene. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus. This may lead to formation of Oncogenes.

Translocation

Translocation is yet another process when two separate chromosomal regions become abnormally fused, often at a characteristic location. A common example is Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukaemia, and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase.

Tumors

A tumor in latin means a swelling but not all swellings are tumors in the modern sense of the term. Some of them may be caused due to inflammation, infections, cysts or fluid filled lesions or due to benign growths. A cancerous tumor has the capacity to grow rapidly and to metastasize or spread to other tissues. Some tumors like leukemias grow as cell suspensions but most grow as solid masses of tissue.

Solid tumor parts

Solid tumors have two distinct parts. One of them is the parenchyma that contains cancer tissues and cells and the other is the stroma that the neoplastic cells induce and in which they are dispersed.

Tumors that originate from epithelial cells have a basal lamina that separates clumps of tumor cells from stroma. However, the basal lamina is often incomplete, especially at points of tumor invasion. The stroma is juxtaposed between malignant cells and normal host tissues and is essential for tumor growth. The stroma contains nonmalignant supporting tissue and includes connective tissue, blood vessels, and, very often, inflammatory cells. All solid tumors require stroma if they are to grow beyond a minimal size of 1 to 2 mm.

In addition, tumors that are cancerous also have the property of new blood vessel formation. Blood vessels are only one component of tumor stroma. In fact, in many tumors, the bulk of stroma comprises interstitial connective tissue, and blood vessels are only a minor component of the stromal mass. The stroma also contains tissues and cells from blood including water and plasma proteins, together with various types and numbers of inflammatory cells. There are in addition proteoglycans and glycosaminoglycans, interstitial collagens (types I, III, and, to a lesser extent, type V), fibrin, fibronectin, fibroblasts etc.