Difference between revisions of "Colorectal tumours"

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====Mismatch repair pathway====
====Mismatch repair pathway====
*Associated with microsatellite instability (MSI).
*Associated with [[microsatellite instability]] (MSI).
*Commonly associated abnormalities in the genes:
*#MLH1.
*#PMS2.
*#MSH2.
*#MSH6.
*Less common abnormalities:
*#PMS1.
*#MLH3.
*#MSH3.
 
=====IHC interpretation=====
*Loss of nuclear staining in nuclei of the tumour = mutation.
**Nuclear staining = normal.
 
MSI staining loss patterns:<ref name=pmid20632815/>
*MLH1 and PMS2 are often lost together, as MLH1 loss results in PMS2 loss.
*MSH2 and MSH6 are often lost together, as MSH2 loss results in MSH6 loss.
 
Implication of MSI staining loss patterns:
*PMS2 & MSH6 can be used as a screen.<ref name=pmid20632815>{{Cite journal  | last1 = Hall | first1 = G. | last2 = Clarkson | first2 = A. | last3 = Shi | first3 = A. | last4 = Langford | first4 = E. | last5 = Leung | first5 = H. | last6 = Eckstein | first6 = RP. | last7 = Gill | first7 = AJ. | title = Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair deficiency screening in colorectal adenocarcinoma. | journal = Pathology | volume = 42 | issue = 5 | pages = 409-13 | month =  | year = 2010 | doi = 10.3109/00313025.2010.493871 | PMID = 20632815 }}</ref>
 
======Etiology/significance loss of staining======
*MSH2 mutations (IHC stain -ve) - often associated with a germline mutation,<ref name=pmid16216036>{{cite journal |author=Mangold E, Pagenstecher C, Friedl W, ''et al.'' |title=Tumours from MSH2 mutation carriers show loss of MSH2 expression but many tumours from MLH1 mutation carriers exhibit weak positive MLH1 staining |journal=J. Pathol. |volume=207 |issue=4 |pages=385–95 |year=2005 |month=December |pmid=16216036 |doi=10.1002/path.1858 |url=}}</ref> while mutations in MLH1 are usually sporatic.<ref>A. Pollett. 2010.</ref>
*PMS2 mutations (IHC stain -ve) - often associated with a germline mutation.<ref name=pmid20205264>{{cite journal |author=Vaughn CP, Robles J, Swensen JJ, ''et al.'' |title=Clinical analysis of PMS2: mutation detection and avoidance of pseudogenes |journal=Hum. Mutat. |volume=31 |issue=5 |pages=588–93 |year=2010 |month=May |pmid=20205264 |doi=10.1002/humu.21230 |url=}}</ref>
 
 
How to remember the more important MSI stuff:
*The ''MSHs'' are paired together.
**''MSH'' (Mount Sinai Hospital) is where they started it in the city.
**''PMS'' sucks... it's with the other one (MLH).
*The higher numbers in the pairings ('''P'''MS2, '''M'''SH6) are the screening tests ('''''H'''igh Screen '''P'''ass'').
*The ''2''s (MSH2, PMS2) are associated with germline mutations (''Four legs good two legs bad!'').


===Other ancillary studies===
===Other ancillary studies===
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