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Difference between revisions of "Colorectal tumours"
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→Pathogenesis: more
(→Others: mucinous carcinoma note) |
(→Pathogenesis: more) |
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#*#MSH3. | #*#MSH3. | ||
====IHC interpretation==== | |||
* | *Loss of nuclear staining in nuclei of the tumour = mutation. | ||
**MLH1 and PMS2 are lost together. | **Nuclear staining = normal. | ||
**MSH2 and MSH6 are lost together. | |||
** | 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> | |||
How to remember this 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 (PMS2, MSH6) are the screening tests. | |||
*The ''2''s (MSH2, PMS2) are associated with germline mutations (''Four legs good two legs bad.''). | |||
====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> | *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> | *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> | ||
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====BRAF V600E mutation==== | ====BRAF V600E mutation==== | ||
Features:<ref name=pmid20635392/> | Features:<ref name=pmid20635392/> | ||
*Independently | *Independently associated with BRAF V600E: | ||
**Usually older (>70 years old). | **Usually older (>70 years old). | ||
**Female gender | **Female gender. | ||
**Right-sided tumour location. | **Right-sided tumour location. | ||
*Worse prognosis - in the context of metastatic disease. | *Worse prognosis - in the context of metastatic disease. | ||