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To view the pathophysiology of familial adenomatous polyposis (FAP), click [[Familial adenomatous polyposis pathophysiology|'''here''']]<br>
To view the pathophysiology of familial adenomatous polyposis (FAP), click [[Familial adenomatous polyposis pathophysiology|'''here''']]<br>
To view the pathophysiology of hereditary nonpolyposis colorectal cancer (HNPCC), click [[Hereditary nonpolyposis colorectal cancer pathophysiology|'''here''']]<br><br>
To view the pathophysiology of hereditary nonpolyposis colorectal cancer (HNPCC), click [[Hereditary nonpolyposis colorectal cancer pathophysiology|'''here''']]<br><br>
{{CMG}} {{AE}} Saarah T. Alkhairy, M.D., Elliot B. Tapper, M.D.
{{CMG}} {{AE}} Saarah T. Alkhairy, M.D., {{RAK}}, Elliot B. Tapper, M.D.


==Overview==
==Overview==
The pathogenesis of colorectal carcinoma (CRC) involves genetic instability, epigenetic alteration, [[chronic inflammation]], [[oxidative stress]], and intestinal [[microbiota]]. Some examples of the types of colorectal carcinoma that can be linked to genetics are hereditary nonpolyposis colon cancer ([[HNPCC]]), [[familial adenomatous polyposis]] ([[FAP]]), and MUTYH-associated polyposis ([[MAP]]). Right-sided and left-sided tumors differ in their gross pathology. Depending on glandular architecture, cellular pleomorphism, and mucosecretion of the predominant pattern, adenocarcinoma may present in three degrees of differentiation: well, moderately, and poorly differentiated.
The pathogenesis of colorectal carcinoma (CRC) involves the molecular pathways for both sporadic and colitis-associated CRC. Sporadic instability originates from the [[epithelial cells]] that line the [[colon]] or [[rectum]]. Colitis-associated CRC includes genetic instability, [[Epigenetic|epigenetic alteration]], [[chronic inflammation]], [[oxidative stress]], and intestinal [[microbiota]]. According to the World Health Organization (WHO) histological classification, most colorectal tumors are carcinomas of which almost 90% are adenocarcinomas.


==Pathogenesis==
==Pathogenesis==
At a microbiological level, the development of the colorectal cancers (CRC) can be linked to defects within the [[cell cycle]]<ref name="pmid21190461">{{cite journal |author=Scully R |title=The spindle-assembly checkpoint, aneuploidy, and gastrointestinal cancer |journal=[[The New England Journal of Medicine]] |volume=363 |issue=27 |pages=2665–6 |year=2010 |month=December |pmid=21190461 |doi=10.1056/NEJMe1008017 |url=http://www.nejm.org/doi/abs/10.1056/NEJMe1008017?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2011-12-12}}</ref>. Although its is poorly understood, the following five factors are recognized to be responsible for its neoplastic changes<ref name="Kim2014">{{cite journal|last1=Kim|first1=Eun Ran|title=Colorectal cancer in inflammatory bowel disease: The risk, pathogenesis, prevention and diagnosis|journal=World Journal of Gastroenterology|volume=20|issue=29|year=2014|pages=9872|issn=1007-9327|doi=10.3748/wjg.v20.i29.9872}}</ref>:
The pathogenesis of colorectal carcinoma (CRC) involves the molecular pathways for both sporadic and colitis-associated CRC.
*Genetic instability
*Epigenetic alteration
*[[Chronic inflammation]]
*[[Oxidative stress]]
*Intestinal [[microbiota]]


===Genetic instability===
===Sporadic colorectal cancers===
*[[Aneuploidy]] is demonstrated in about 50%-90% of cancers
*A loss of adenomatous polyposis ([[APC]]) function is common in sporadic CRC
*A loss of P53 function is common in colitis-associated CRC
*The following are two types of genomic instability
:*Chromosomal instability (CIN) occurs when either whole chromosomes or parts of chromosomes are duplicated or deleted; it has a 85% frequency
:*[[Microsatellite instability]] (MSI) is the condition of genetic hypermutability that results from impaired DNA mismatch repair; it a 15% frequency


===Epigenetic alteration===
The picture below depicts the molecular pathogenesis of sporadic colon cancer:<ref name="Kim2014">{{cite journal|last1=Kim|first1=Eun Ran|title=Colorectal cancer in inflammatory bowel disease: The risk, pathogenesis, prevention and diagnosis|journal=World Journal of Gastroenterology|volume=20|issue=29|year=2014|pages=9872|issn=1007-9327|doi=10.3748/wjg.v20.i29.9872}}</ref>
*Sporadic CRC can develop from [[dysplasia]] in 1 or 2 foci of the colon
[[Image:Sporadic Colon Cancer3.jpg|center|1000x1000px|frame|Molecular pathogenesis of sporadic colon cancer, (ɔ) Image courtesy of WikiDoc.org]]
*Colitis-associated CRC can develop from multifocal dysplasia
Sporadic colorectal cancer originates from the [[epithelial cells]] that line the [[colon]] or [[rectum]]; it may involve the following:<ref name="pmid20018966">{{cite journal| author=Markowitz SD, Bertagnolli MM| title=Molecular origins of cancer: Molecular basis of colorectal cancer. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 25 | pages= 2449-60 | pmid=20018966 | doi=10.1056/NEJMra0804588 | pmc=PMC2843693 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20018966  }} </ref>
:*This indicates a field change effect where large areas of cells within the colon are affected by carcinogenic alterations
*'''[[APC gene]]'''
:*Produces the APC protein, which prevents the accumulation of [[β-catenin]] protein (responsible for stem cell renewal)


===Chronic inflammation===
:* Mutation of the APC protein leads to the accumulation of [[β-catenin]] protein and causes inappropriately high levels of stem cell renewal.
*[[COX-2]] is triggered by inflammatory stimuli such as [[IL-1]], [[IFN-γ, and [[TNF-α]]  
*'''[[TP53|TP53 gene]]'''
*COX-2 expression is elevated in nearly 85% of [[adenocarcinomas]]
:*Produces the [[P53 (protein)|p53 protein]], which monitors cell division and promotes [[apoptosis]] if there are cell defects
:*[[mutation|Mutation]]<nowiki/>[[mutation|s]] result in loss of control over cell division or apoptosis
*'''[[TGF beta|TGF-β]] and [[DCC]] (Deleted in Colorectal Cancer)'''
:*Usually responsible for [[apoptosis]], but deactivated in colorectal cancer
*'''[[Oncogenes]]'''
:*Stimulate cellular division
:*Mutations lead to over-activation of [[cell proliferation]]


===Oxidative stress===
===Colitis-associated colorectal cancers===  
*[[Oxidative stress]] results from inflammatory reactions which include inflammatory cells, activated neutrophils, and [[macrophages]]
*[[Macrophages]] produce large amounts of reactive oxygen and nitrogen species (RONS)
*RONs can interact with key genes involved in carcinogenic pathways such as [[P53]] and [[DNA mismatch repair]] genes


===Intestinal microbiota===
The picture below depicts the molecular pathogenesis of colitis-associated colon cancer:<ref name="Kim2014">{{cite journal|last1=Kim|first1=Eun Ran|title=Colorectal cancer in inflammatory bowel disease: The risk, pathogenesis, prevention and diagnosis|journal=World Journal of Gastroenterology|volume=20|issue=29|year=2014|pages=9872|issn=1007-9327|doi=10.3748/wjg.v20.i29.9872}}</ref>
*The mechanism is still unclear


==Genetics==
[[Image:Colitis-associated colon cancer.jpg|center|800x800px|frame|Molecular pathogenesis of colitis-associated colon cancer, (ɔ) Image courtesy of WikiDoc.org]]
CRC can be grouped into three categories from a genetic perspective<ref name="pmid25276405">{{cite journal| author=Schlussel AT, Gagliano RA, Seto-Donlon S, Eggerding F, Donlon T, Berenberg J et al.| title=The evolution of colorectal cancer genetics-Part 1: from discovery to practice. | journal=J Gastrointest Oncol | year= 2014 | volume= 5 | issue= 5 | pages= 326-35 | pmid=25276405 | doi=10.3978/j.issn.2078-6891.2014.069 | pmc=PMC4173047 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25276405  }} </ref>:
 
*Sporadic (75% of cases) - no apparent indications of a hereditary component
At a [[microbiological]] level, the development of colitis-associated colorectal cancers (CRC) can be linked to defects within the [[cell cycle]].<ref name="pmid21190461">{{cite journal |author=Scully R |title=The spindle-assembly checkpoint, aneuploidy, and gastrointestinal cancer |journal=[[The New England Journal of Medicine]] |volume=363 |issue=27 |pages=2665–6 |year=2010|pmid=21190461 |doi=10.1056/NEJMe1008017 |url=http://www.nejm.org/doi/abs/10.1056/NEJMe1008017?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2011-12-12}}</ref>  
*[[Familial]] (20% of cases) - multifactorial hereditary factors or common exposures to non-genetic risk factors or both
*[[Hereditary]] (10% of cases)
:*Hereditary nonpolyposis colon cancer ([[HNPCC]]) also known as Lynch Syndrome results from mutations in hMLH1, hMSH2, hMSH6, and PMS2
:*[[Familial adenomatous polyposis]] ([[FAP]]) results from mutations in the APC gene located on chromosome 5p22.2
:*MUTYH-associated polyposis ([[MAP]]) results from biallelic mutation of the MutY, E. Coli, Homolog gene which functions to remove [[adenine]] residues mispaired with 8-hydroxyguanine in DNA
<gallery widths=200px>


ImageName.jpg | Molecular pathogenesis of sporadic colon cancer and colitis-associated colon cancer  <br> [http://http://ajpgi.physiology.org/content/287/1/G7/ <font size="-2">''Adapted from APS Journals''</font>]
Although it is poorly understood, the following five factors may be responsible for its [[neoplastic]] changes:<ref name="Kim2014">{{cite journal|last1=Kim|first1=Eun Ran|title=Colorectal cancer in inflammatory bowel disease: The risk, pathogenesis, prevention and diagnosis|journal=World Journal of Gastroenterology|volume=20|issue=29|year=2014|pages=9872|issn=1007-9327|doi=10.3748/wjg.v20.i29.9872}}</ref>
*'''Genetic instability<ref name="pmid1118685">{{cite journal| author=Zivić R, Bjelaković G, Koraćević D| title=[Amino acid constitution of the urine in children with rheumatic fever]. | journal=Reumatizam | year= 1975 | volume= 22 | issue= 1 | pages= 21-5 | pmid=1118685 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1118685  }} </ref>'''
**Chromosomal instability (CIN) occurs when either whole [[chromosomes]] or parts of [[chromosomes]] are duplicated or deleted; it occurs with 85% frequency.
**[[Microsatellite instability]] (MSI) is the condition of genetic hypermutability that results from impaired [[DNA mismatch repair]]; it occurs with 15% frequency.


*'''Epigenetic alteration'''
**Sporadic CRC can develop from [[dysplasia]] in 1 or 2 foci of the colon, while colitis-associated CRC can develop from multifocal dysplasia.<ref name="pmid12702969">{{cite journal| author=Itzkowitz S| title=Colon carcinogenesis in inflammatory bowel disease: applying molecular genetics to clinical practice. | journal=J Clin Gastroenterol | year= 2003 | volume= 36 | issue= 5 Suppl | pages= S70-4; discussion S94-6 | pmid=12702969 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12702969  }} </ref><ref name="pmid19589728">{{cite journal| author=Kraus S, Arber N| title=Inflammation and colorectal cancer. | journal=Curr Opin Pharmacol | year= 2009 | volume= 9 | issue= 4 | pages= 405-10 | pmid=19589728 | doi=10.1016/j.coph.2009.06.006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19589728  }} </ref>
**This indicates a field change effect where large areas of cells within the colon are affected by [[carcinogenic]] alterations.
*[[Chronic inflammation|'''Chronic inflammation''']]<ref name="pmid23898071">{{cite journal| author=Elzagheid A, Emaetig F, Alkikhia L, Buhmeida A, Syrjänen K, El-Faitori O et al.| title=High cyclooxygenase-2 expression is associated with advanced stages in colorectal cancer. | journal=Anticancer Res | year= 2013 | volume= 33 | issue= 8 | pages= 3137-43 | pmid=23898071 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23898071  }} </ref>
**[[COX-2]] is triggered by inflammatory stimuli such as [[IL-1]], [[Interferon-gamma|IFN-γ,]] and [[TNF-α]].
**[[COX-2]] expression is elevated in approximately 85% of [[adenocarcinomas]].
*[[Oxidative stress|'''Oxidative stress''']]<ref name="pmid21530747">{{cite journal| author=Ullman TA, Itzkowitz SH| title=Intestinal inflammation and cancer. | journal=Gastroenterology | year= 2011 | volume= 140 | issue= 6 | pages= 1807-16 | pmid=21530747 | doi=10.1053/j.gastro.2011.01.057 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21530747  }} </ref>
**[[Oxidative stress]] results from inflammatory reactions which include inflammatory cells, activated [[neutrophils]], and [[macrophages]].
**[[Macrophages]] produce large amounts of [[reactive oxygen]] and [[nitrogen species]].
**These reactive oxygen and nitrogen species can interact with key genes involved in carcinogenic pathways such as [[P53]] and [[DNA mismatch repair]] genes.


</gallery>
*'''Intestinal [[microbiota]]'''<ref name="pmid11472326">{{cite journal| author=O'Mahony L, Feeney M, O'Halloran S, Murphy L, Kiely B, Fitzgibbon J et al.| title=Probiotic impact on microbial flora, inflammation and tumour development in IL-10 knockout mice. | journal=Aliment Pharmacol Ther | year= 2001 | volume= 15 | issue= 8 | pages= 1219-25 | pmid=11472326 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11472326  }} </ref>
**The Modification of enteric flora by probiotic [[lactobacilli]] is a proposed mechanism that may contribute to the development of colitis-associated cancer.


==Gross Pathology==
==Genetics==
*Right-sided tumors (ascending colon and [[cecum]]) tends to grow outwards from one location in the bowel wall (exophytic)
From a genetic standpoint, colorectal cancer can be divided into three categories:<ref name="pmid25276405">{{cite journal| author=Schlussel AT, Gagliano RA, Seto-Donlon S, Eggerding F, Donlon T, Berenberg J et al.| title=The evolution of colorectal cancer genetics-Part 1: from discovery to practice. | journal=J Gastrointest Oncol | year= 2014 | volume= 5 | issue= 5 | pages= 326-35 | pmid=25276405 | doi=10.3978/j.issn.2078-6891.2014.069 | pmc=PMC4173047 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25276405  }} </ref>
*'''Sporadic''' (75% of cases)
**No indication of a hereditary component
*[[Familial|'''Familial''']] (20% of cases)
**Resulting from [[Multifactorial inheritance|multifactorial hereditary]] factors and/or environmental exposures to non-genetic risk factors
*[[Hereditary|'''Hereditary''']] (10% of cases)
:*[[Hereditary nonpolyposis colorectal cancer|Hereditary nonpolyposis colon cancer]] ([[HNPCC]]) also known as [[Lynch Syndrome I|Lynch Syndrome]] results from mutations in hMLH1, hMSH2, hMSH6, and PMS2
:*[[Familial adenomatous polyposis]] ([[FAP]]) results from mutations in the [[APC gene]] located on chromosome 5p22.2
:*MUTYH-associated polyposis ([[MAP]]) results from biallelic mutation of the MutY, [[E. Coli]], Homolog gene which functions to remove [[adenine]] residues mispaired with 8-hydroxyguanine in DNA


*Left-sided tumours tend to be circumferential
[[Image:796px-Colon_cancer_2.jpg‎|200px|thumb|right|Appearance of the inside of the colon showing one invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor). - Source: librepathology.org]]


[[Image:796px-Colon_cancer_2.jpg‎|200px|thumb|center|Appearance of the inside of the colon showing one invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor).]]
==Gross Pathology==
*On gross pathology, a polypoid or fungating exophytic (growing outwards) lesion is characteristic of right-sided colorectal tumors including the ascending colon and cecum.<ref name="pmid21969498">{{cite journal| author=Weiss JM, Pfau PR, O'Connor ES, King J, LoConte N, Kennedy G et al.| title=Mortality by stage for right- versus left-sided colon cancer: analysis of surveillance, epidemiology, and end results--Medicare data. | journal=J Clin Oncol | year= 2011 | volume= 29 | issue= 33 | pages= 4401-9 | pmid=21969498 | doi=10.1200/JCO.2011.36.4414 | pmc=3221523 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21969498  }}</ref>
*Left-sided tumours tend to be circumferential and annular producing an "apple-core" appearance on barium enema x-ray.<ref name="pmid21969498" />


[[Image:Colonic carcinoid (1) Endoscopic resection.jpg|thumb|right|200px|Histopathologic image of colonic carcinoid stained by hematoxylin and eosin. - By No machine-readable author provided. KGH assumed (based on copyright claims). - No machine-readable source provided. Own work assumed (based on copyright claims)., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=453828]]
==Microscopic Pathology==
==Microscopic Pathology==
*Tumor cells form irregular tubular structures, harboring pleuristratification, multiple lumens, and reduced stroma
According to the World Health Organization (WHO) histological classification, most colorectal tumors are carcinomas of which almost 90% are adenocarcinomas:<ref name="pmid10888773">{{cite journal| author=Compton CC, Fielding LP, Burgart LJ, Conley B, Cooper HS, Hamilton SR et al.| title=Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. | journal=Arch Pathol Lab Med | year= 2000 | volume= 124 | issue= 7 | pages= 979-94 | pmid=10888773 | doi=10.1043/0003-9985(2000)124<0979:PFICC>2.0.CO;2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10888773  }}</ref>
*Sometimes, tumor cells are discohesive and secrete [[mucus]], which invades the [[interstitium]] producing large pools of mucus/colloid (optically "empty" spaces)
*Carcinomas
*If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery (signet-ring cell)
**Adenocarcinoma
*Depending on glandular architecture, cellular pleomorphism, and mucosecretion of the predominant pattern, adenocarcinoma may present in three degrees of differentiation: well, moderately, and poorly differentiated<ref[http://www.pathologyatlas.ro/Colon%20Cancer.html Pathology atlas (in Romanian)]</ref>
**Mucinous adenocarcinoma
**Signet-ring cell carcinoma
**Small cell carcinoma
**Adenosquamous carcinoma
**Squamous cell
**Medullary carcinoma
**Undifferentiated carcinoma
*Neuroendocrine neoplasms
*Hamartomas
*Mesenchymas tumors
*Lymphomas


[[Image:Colonic carcinoid (1) Endoscopic resection.jpg|thumb|center|Histopathologic image of colonic carcinoid stained by hematoxylin and eosin.]]


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===References===
===Video===
 
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==References==
{{Reflist|2}}
{{Reflist|2}}


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To view the pathophysiology of familial adenomatous polyposis (FAP), click here
To view the pathophysiology of hereditary nonpolyposis colorectal cancer (HNPCC), click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Saarah T. Alkhairy, M.D., Roukoz A. Karam, M.D.[2], Elliot B. Tapper, M.D.

Overview

The pathogenesis of colorectal carcinoma (CRC) involves the molecular pathways for both sporadic and colitis-associated CRC. Sporadic instability originates from the epithelial cells that line the colon or rectum. Colitis-associated CRC includes genetic instability, epigenetic alteration, chronic inflammation, oxidative stress, and intestinal microbiota. According to the World Health Organization (WHO) histological classification, most colorectal tumors are carcinomas of which almost 90% are adenocarcinomas.

Pathogenesis

The pathogenesis of colorectal carcinoma (CRC) involves the molecular pathways for both sporadic and colitis-associated CRC.

Sporadic colorectal cancers

The picture below depicts the molecular pathogenesis of sporadic colon cancer:[1]

Molecular pathogenesis of sporadic colon cancer, (ɔ) Image courtesy of WikiDoc.org

Sporadic colorectal cancer originates from the epithelial cells that line the colon or rectum; it may involve the following:[2]

  • Produces the APC protein, which prevents the accumulation of β-catenin protein (responsible for stem cell renewal)
  • Mutation of the APC protein leads to the accumulation of β-catenin protein and causes inappropriately high levels of stem cell renewal.
  • Produces the p53 protein, which monitors cell division and promotes apoptosis if there are cell defects
  • Mutations result in loss of control over cell division or apoptosis
  • TGF-β and DCC (Deleted in Colorectal Cancer)
  • Usually responsible for apoptosis, but deactivated in colorectal cancer

Colitis-associated colorectal cancers

The picture below depicts the molecular pathogenesis of colitis-associated colon cancer:[1]

Molecular pathogenesis of colitis-associated colon cancer, (ɔ) Image courtesy of WikiDoc.org

At a microbiological level, the development of colitis-associated colorectal cancers (CRC) can be linked to defects within the cell cycle.[3]

Although it is poorly understood, the following five factors may be responsible for its neoplastic changes:[1]

  • Intestinal microbiota[9]
    • The Modification of enteric flora by probiotic lactobacilli is a proposed mechanism that may contribute to the development of colitis-associated cancer.

Genetics

From a genetic standpoint, colorectal cancer can be divided into three categories:[10]

  • Sporadic (75% of cases)
    • No indication of a hereditary component
  • Familial (20% of cases)
  • Hereditary (10% of cases)
Appearance of the inside of the colon showing one invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor). - Source: librepathology.org

Gross Pathology

  • On gross pathology, a polypoid or fungating exophytic (growing outwards) lesion is characteristic of right-sided colorectal tumors including the ascending colon and cecum.[11]
  • Left-sided tumours tend to be circumferential and annular producing an "apple-core" appearance on barium enema x-ray.[11]
Histopathologic image of colonic carcinoid stained by hematoxylin and eosin. - By No machine-readable author provided. KGH assumed (based on copyright claims). - No machine-readable source provided. Own work assumed (based on copyright claims)., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=453828

Microscopic Pathology

According to the World Health Organization (WHO) histological classification, most colorectal tumors are carcinomas of which almost 90% are adenocarcinomas:[12]

  • Carcinomas
    • Adenocarcinoma
    • Mucinous adenocarcinoma
    • Signet-ring cell carcinoma
    • Small cell carcinoma
    • Adenosquamous carcinoma
    • Squamous cell
    • Medullary carcinoma
    • Undifferentiated carcinoma
  • Neuroendocrine neoplasms
  • Hamartomas
  • Mesenchymas tumors
  • Lymphomas



References

  1. ↑ 1.0 1.1 1.2 Kim, Eun Ran (2014). "Colorectal cancer in inflammatory bowel disease: The risk, pathogenesis, prevention and diagnosis". World Journal of Gastroenterology. 20 (29): 9872. doi:10.3748/wjg.v20.i29.9872. ISSN 1007-9327.
  2. ↑ Markowitz SD, Bertagnolli MM (2009). "Molecular origins of cancer: Molecular basis of colorectal cancer". N Engl J Med. 361 (25): 2449–60. doi:10.1056/NEJMra0804588. PMC 2843693. PMID 20018966.
  3. ↑ Scully R (2010). "The spindle-assembly checkpoint, aneuploidy, and gastrointestinal cancer". The New England Journal of Medicine. 363 (27): 2665–6. doi:10.1056/NEJMe1008017. PMID 21190461. Retrieved 2011-12-12.
  4. ↑ Zivić R, Bjelaković G, Koraćević D (1975). "[Amino acid constitution of the urine in children with rheumatic fever]". Reumatizam. 22 (1): 21–5. PMID 1118685.
  5. ↑ Itzkowitz S (2003). "Colon carcinogenesis in inflammatory bowel disease: applying molecular genetics to clinical practice". J Clin Gastroenterol. 36 (5 Suppl): S70–4, discussion S94-6. PMID 12702969.
  6. ↑ Kraus S, Arber N (2009). "Inflammation and colorectal cancer". Curr Opin Pharmacol. 9 (4): 405–10. doi:10.1016/j.coph.2009.06.006. PMID 19589728.
  7. ↑ Elzagheid A, Emaetig F, Alkikhia L, Buhmeida A, Syrjänen K, El-Faitori O; et al. (2013). "High cyclooxygenase-2 expression is associated with advanced stages in colorectal cancer". Anticancer Res. 33 (8): 3137–43. PMID 23898071.
  8. ↑ Ullman TA, Itzkowitz SH (2011). "Intestinal inflammation and cancer". Gastroenterology. 140 (6): 1807–16. doi:10.1053/j.gastro.2011.01.057. PMID 21530747.
  9. ↑ O'Mahony L, Feeney M, O'Halloran S, Murphy L, Kiely B, Fitzgibbon J; et al. (2001). "Probiotic impact on microbial flora, inflammation and tumour development in IL-10 knockout mice". Aliment Pharmacol Ther. 15 (8): 1219–25. PMID 11472326.
  10. ↑ Schlussel AT, Gagliano RA, Seto-Donlon S, Eggerding F, Donlon T, Berenberg J; et al. (2014). "The evolution of colorectal cancer genetics-Part 1: from discovery to practice". J Gastrointest Oncol. 5 (5): 326–35. doi:10.3978/j.issn.2078-6891.2014.069. PMC 4173047. PMID 25276405.
  11. ↑ 11.0 11.1 Weiss JM, Pfau PR, O'Connor ES, King J, LoConte N, Kennedy G; et al. (2011). "Mortality by stage for right- versus left-sided colon cancer: analysis of surveillance, epidemiology, and end results--Medicare data". J Clin Oncol. 29 (33): 4401–9. doi:10.1200/JCO.2011.36.4414. PMC 3221523. PMID 21969498.
  12. ↑ Compton CC, Fielding LP, Burgart LJ, Conley B, Cooper HS, Hamilton SR; et al. (2000). "Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999". Arch Pathol Lab Med. 124 (7): 979–94. doi:10.1043/0003-9985(2000)124<0979:PFICC>2.0.CO;2. PMID 10888773.


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