Field cancerization or field effect (also termed field change, field change cancerization, field carcinogenesis, cancer field effect or premalignant field defect) is a biological process in which large areas of

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

s at a tissue surface or within an organ are affected by carcinogenic alterations. The process arises from exposure to an injurious environment, often over a lengthy period.

How it arises

The initial step in field cancerization is associated with various molecular lesions such as acquired

genetic mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s and

epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

changes, occurring over a widespread, multi-focal "field". These initial molecular changes may subsequently progress to

cytologically Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...

recognizable

premalignant A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased ...

foci of

dysplasia Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs (macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic ...

, and eventually to

carcinoma in situ Carcinoma ''in situ'' (CIS) is a group of abnormal cells. While they are a form of neoplasm, there is disagreement over whether CIS should be classified as cancer. This controversy also depends on the exact CIS in question (i.e. cervical, skin, bre ...

(CIS) or

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

. The image of a longitudinally opened colon resection on this page shows an area of a colon resection that likely has a field cancerization or field defect. It has one cancer and four premalignant polyps. Field cancerization can occur in any tissue. Prominent examples of field cancerization include premalignant field defects in

head and neck cancer Head and neck cancer develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptoms ...

lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

Barrett's esophagus Barrett's esophagus is a condition in which there is an abnormal (metaplastic) change in the mucosal cells lining the lower portion of the esophagus, from stratified squamous epithelium to simple columnar epithelium with interspersed goblet ce ...

, skin, breast ducts and bladder. Field cancerization has implications for cancer surveillance and treatment. Despite adequate resection and being

histologically Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...

normal, the remaining locoregional tissue has an increased risk for developing multiple independent cancers, either

synchronous Synchronization is the coordination of events to operate a system in unison. For example, the conductor of an orchestra keeps the orchestra synchronized or ''in time''. Systems that operate with all parts in synchrony are said to be synchronou ...

ly or metachronously.

Common early carcinogenic alterations

A common carcinogenic alteration, found in many cancers and in their adjacent field defects from which the cancers likely arose, is reduced expression of one or more DNA repair enzymes. Since reduced DNA repair expression is often present in a field cancerization or a field defect, it is likely to have been an early step in progression to the cancer. Field defects associated with gastrointestinal tract cancers also commonly displayed reduced apoptosis competence, aberrant proliferation and genomic instability. Field defects of the gastrointestinal tract that show those common faults occurred in the oropharynx, esophagus, stomach, bile duct, pancreas, small intestine and colon/rectum.

Pattern of alterations in a field defect

The field defect adjacent to a colon cancer consists of the inner surface of the colon (the epithelium) that has about 1 million crypts (indentations in the surface of the epithelium). Each crypt has about 5,000 cells in the shape of a test-tube and all 5,000 cells of the crypt are generated from the few stem cells at the base of the crypt. The stem cells at the base of the crypt can undergo "crypt conversion" where a stem cell with a selective advantage takes over the stem cell niche, and all cells of that crypt display consistent expression (high or low) of a protein being evaluated. The diagram shows results obtained by Facista et al. A particular colon resection from a colon cancer patient was evaluated for expression of 3 different DNA repair enzymes:

Ku86 Ku80 is a protein that, in humans, is encoded by the ''XRCC5'' gene. Together, Ku70 and Ku80 make up the Ku heterodimer, which binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair ...

(active in the non-homologous end joining pathway),

ERCC1 DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ''ERCC1'' gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination. Many aspects of these two gene ...

(active in the nucleotide excision DNA repair pathway) and

PMS2 Mismatch repair endonuclease PMS2 is an enzyme that in humans is encoded by the ''PMS2'' gene. Function This gene is one of the PMS2 gene family members which are found in clusters on chromosome 7. Human PMS2 related genes are located at bands ...

(active in the mismatch DNA repair pathway). The percent of crypts in 6 tissue samples taken within the field defect were evaluated for frequency of high levels of expression of each of the repair proteins. Almost every crypt in all tissue samples from this patient showed high expression of KU86. However, the majority of crypts in all 6 tissue samples were reduced or absent in protein expression of ERCC1 and PMS2. The crypts with reduced or absent expression of ERCC1 or PMS2 usually occurred in large patches of adjacent crypts. Both ERCC1 and PMS2, in these tissue samples, were thought to be deficient due to epigenetic alterations.

References

External links

{{cite journal, title=Field cancerization and local relapse. , last=Leemans, first=CR, author2=Braakhuis, BJM , author3=Brakenhoff RH. , date=January 2011, journal=Nature Reviews Cancer , volume=11, issue=1, pages=9–22 , doi=10.1038/nrc2982, pmid = 21160525 Biological processes