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
cells 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, mitosis ...
s and
epigenetic
In biology, epigenetics is the study of changes in gene expression that happen without changes to the DNA sequence. The Greek prefix ''epi-'' (ἐπι- "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in ...
changes, occurring over a widespread, multi-focal "field".
These initial molecular changes may subsequently progress to
cytologically recognizable
premalignant foci of
dysplasia, and eventually to
carcinoma in situ (CIS) or
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
.
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 is a general term encompassing multiple cancers that can develop in the head and neck region. These include cancers of the mouth, tongue, gums and lips (oral cancer), voice box ( laryngeal), throat ( nasopharyngeal, orophary ...
,
lung cancer
Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...
,
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...
,
Barrett's esophagus
Barrett's esophagus is a condition in which there is an abnormal ( metaplastic) change in the mucosal cells that line the lower part of the esophagus. The cells change from stratified squamous epithelium to simple columnar epithelium, intersper ...
,
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 that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...
normal, the remaining locoregional tissue has an increased risk for developing multiple independent cancers, either
synchronously 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 (active in the non-homologous end joining pathway),
ERCC1 (active in the nucleotide excision DNA repair pathway) and
PMS2 (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