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{{Colon cancer}}
{{Colon cancer}}
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>
{{CMG}} {{AE}} Saarah T. Alkhairy, M.D., {{RAK}}, Elliot B. Tapper, M.D.


'''Editor(s)-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com] Phone:617-632-7753; Elliot B. Tapper, M.D., Beth Israel Deaconess Medical Center
==Overview==
{{MJM}};{{AE}}{{SM}}
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.


==Pathophysiology==
==Pathogenesis==
At a microbiological level, the development of the colon cancers (as well as other cancers) 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>.  In a normal cell cycle, [[kinetochores]], which are located at the [[centromere]] of the [[chromosomes]], will attach to the [[mitotic spindle]] fibers. The [[sister chromatids]] will be pulled to either side of the [[cell]], creating the necessities for two separate cells.  If the kinetochore is not properly attached to the spindle, a signal is generated that stops the [[mitotic division]] until the attachment is fixed. This signal causing system is referred to as the [[spindle-assembly checkpoint]].  If there are mutations in this checkpoint, then [[mitosis]] can continue without repairing detached kinetochores.  This will ultimately lead to [[mis-segregation]] of chromosomes as well as [[aneuploidy]], which is an abnormal amount of chromosomes in a cell<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>.  A predisposition to colon cancer may come from this mechanism.
The pathogenesis of colorectal carcinoma (CRC) involves the molecular pathways for both sporadic and colitis-associated CRC.


==Pathology==
===Sporadic colorectal cancers===
The [[pathology]] of the tumor is usually reported from the analysis of tissue taken from a biopsy or surgery.  A pathology report will usually contain a description of [[histology|cell type]] and grade.  The most common colon cancer cell type is [[adenocarcinoma]] which accounts for 95% of cases. Other, rarer types include [[lymphoma]] and [[squamous cell carcinoma]].


===Gross Pathology===
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>
Adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the colorectal mucosa.  It invades the wall, infiltrating the [[muscularis mucosae]], the [[submucosa]] and thence the muscularis propria. Cancers on the right side (ascending colon and [[cecum]]) tend to be exophytic, that is, the tumour grows outwards from one location in the bowel wall.  This very rarely causes obstruction of [[feces]], and presents with symptoms such as [[anemia]].  Left-sided tumours tend to be circumferential, and can obstruct the bowel much like a napkin ring.
[[Image:Sporadic Colon Cancer3.jpg|center|1000x1000px|frame|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:<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>
*'''[[APC gene]]'''
:*Produces the APC protein, which prevents the accumulation of [[β-catenin]] protein (responsible for stem cell renewal)


[[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).]]
:* Mutation of the APC protein leads to the accumulation of [[β-catenin]] protein and causes inappropriately high levels of stem cell renewal.
*'''[[TP53|TP53 gene]]'''
:*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]]


===Microscopic Pathology===
===Colitis-associated colorectal cancers===  
Tumor cells form irregular tubular structures, harboring pleuristratification, multiple lumens, reduced stroma ("back to back" aspect). Sometimes, tumor cells are discohesive and secrete mucus, which invades the interstitium producing large pools of mucus/colloid (optically "empty" spaces) - ''mucinous (colloid)'' adenocarcinoma, poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery - "signet-ring cell." Depending on glandular architecture, cellular pleomorphism, and mucosecretion of the predominant pattern, adenocarcinoma may present three degrees of differentiation: well, moderately, and poorly differentiated. <ref>[http://www.pathologyatlas.ro/Colon%20Cancer.html Pathology atlas (in Romanian)]</ref>


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


<br clear="left"/>
[[Image:Colitis-associated colon cancer.jpg|center|800x800px|frame|Molecular pathogenesis of colitis-associated colon cancer, (ɔ) Image courtesy of WikiDoc.org]]


===Genetics===
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>  
As of 1993, there was a discovery made in the mechanism of the development of colon cancers.  It was found that [[HNPCC]] is caused by [[germline]] [[mutations]] of [[mismatch repair genes]]<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>.  A '''germline mutation''' is defined as a [[gene]] change in a body's [[reproductive cell]] that becomes incorporated into the [[DNA]] of every [[cell]] in the body of the [[offspring]].
Colorectal cancer is a disease originating from the [[epithelium|epithelial cells]] lining the [[gastrointestinal tract]].  [[Hereditary disease|Hereditary]] or [[somatic cell|somatic]] [[mutation]]s in specific [[DNA]] sequences, among which are included [[DNA replication]] or [[DNA repair]] [[gene]]s<ref>{{cite journal |author=Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M|title=Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis|journal=Nature|volume=363|issue=6429|pages=558-61|year=1993|url=http://dx.doi.org/10.1038/363558a0|pmid=8505985}}</ref>, and also the [[Adenomatous polyposis coli|APC]], [[Ras|K-Ras]], [[NOD2]] and [[p53]] genes, lead to unrestricted cell division.  The exact reason why (and whether) a diet high in fiber might prevent colorectal cancer remains uncertain.  Chronic inflammation, as in [[inflammatory bowel disease]], may predispose patients to malignancy.
Another mechanism involves the WNT gene family.  There are a total of 19 genes in the WNT gene family and they are responsible for providing the instructions to make proteins that are responsible for chemical signaling.  Research has shown that [[up-regulation]] of WNT signaling will cause [[crypt cells]] in the [[intestine]] to [[proliferate]] for longer than normal before they [[differentiate]] and [[migrate]]<ref name="pmid21732829">{{cite journal |author=Dolmans GH, Werker PM, Hennies HC, Furniss D, Festen EA, Franke L, Becker K, van der Vlies P, Wolffenbuttel BH, Tinschert S, Toliat MR, Nothnagel M, Franke A, Klopp N, Wichmann HE, Nürnberg P, Giele H, Ophoff RA, Wijmenga C |title=Wnt signaling and Dupuytren's disease |journal=[[The New England Journal of Medicine]] |volume=365 |issue=4 |pages=307–17 |year=2011 |month=July |pmid=21732829 |doi=10.1056/NEJMoa1101029 |url=http://www.nejm.org/doi/abs/10.1056/NEJMoa1101029?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2011-12-12}}</ref>.  Prolonged proliferation eventually causes [[polyps]] to form, which in turn creates a predisposition to colon cancer.


===Video===
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.


{{#ev:youtube|Sh65aXndqXk}}
*'''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.


==References==
*'''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.
 
==Genetics==
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
 
[[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]]
 
==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==
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>
*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
 
 
<br clear="left" />
===References===
{{Reflist|2}}
{{Reflist|2}}


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Latest revision as of 16:14, 28 February 2019

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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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