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[en] | Field cancerization Skip to content 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.[ 1]
The initial step in field cancerization is associated with various molecular lesions such as acquired genetic mutations and epigenetic changes, occurring over a widespread, multi-focal “field”.[ 2] [ 3] [ 4] [ 5] [ 6] [ 7] [ 8] These initial molecular changes may subsequently progress to cytologically recognizable premalignant foci of dysplasia , and eventually to carcinoma in situ (CIS) or cancer .[ 1] [ 5] 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.[ 1] Prominent examples of field cancerization include premalignant field defects in head and neck cancer ,[ 9] lung cancer ,[ 2] [ 3] colorectal cancer ,[ 10] Barrett’s esophagus ,[ 11] [ 12] [ 13] skin,[ 4] [ 6] [ 8] breast ducts[ 7] [ 14] and bladder.[ 1] [ 15] Field cancerization has implications for cancer surveillance and treatment.[ 3] [ 4] [ 8] [ 11] [ 14] [ 16] Despite adequate resection and being histologically normal, the remaining locoregional tissue has an increased risk for developing multiple independent cancers, either synchronously or metachronously .[ 1] [ 9] [ 17]
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.
Frequency of finding epigenetic reductions in protein expression of DNA repair genes in sporadic cancers and in adjacent field defects Cancer Gene Frequency in Cancer Frequency in Field Defect Ref. Colorectal MGMT 46% 34% [ 18] Colorectal MGMT 47% 11% [ 19] Colorectal MGMT 70% 60% [ 20] Colorectal MSH2 13% 5% [ 19] Colorectal ERCC1 100% 40% [ 21] Colorectal PMS2 88% 50% [ 21] Colorectal XPF 55% 40% [ 21] Head and Neck MGMT 54% 38% [ 22] Head and Neck MLH1 33% 25% [ 23] Head and Neck MLH1 31% 20% [ 24] Stomach MGMT 88% 78% [ 25] Stomach MLH1 73% 20% [ 26] Esophagus MLH1 77%-100% 23%-79% [ 27]
Field defects associated with gastrointestinal tract cancers also commonly displayed reduced apoptosis competence, aberrant proliferation and genomic instability.[ 28] 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).[ 21] 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.[ 21] 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.
^ a b c d e Field cancerization Medical Dictionary – The Free Dictionary McGraw-Hill Concise Dictionary of Modern Medicine. 2002 by The McGraw-Hill Companies, Inc. [1] ^ a b Rubin H (March 2011). “Fields and field cancerization: the preneoplastic origins of cancer: asymptomatic hyperplastic fields are precursors of neoplasia, and their progression to tumors can be tracked by saturation density in culture”. BioEssays . 33 (3): 224–31. doi :10.1002/bies.201000067 . PMID 21254148 . ^ a b c Kadara H (May 2012). “Wistuba II Field cancerization in non-small cell lung cancer: implications in disease pathogenesis” . Proceedings of the American Thoracic Society . 9 (2): 38–42. doi :10.1513/pats.201201-004MS . PMC 5821032 . PMID 22550239 . ^ a b c Braathen LR, Morton CA, Basset-Seguin N, Bissonnette R, Gerritsen MJ, Gilaberte Y, Calzavara-Pinton P, Sidoroff A, Wulf HC, Szeimies RM (2012). “Photodynamic therapy for skin field cancerization: an international consensus. 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