p16 and cancer; basic question

[MirkoCrocop]

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I'm studying nonkeratinizing SCC of the oral cavity and the textbook says it's positive for CK and p16, a tumor suppressor protein that is aberrantly overexpressed in HPV-infected cells. 2 questions:

1) why would overexpression of a tumor suppressor gene be associated with any cancer?

2) if p16 is normally found in cells, how would a (+) stain help at all?

anyone with experience interpreting p16 stain that can help?

thanks in advance!

 

[2121115]

I'm studying nonkeratinizing SCC of the oral cavity and the textbook says it's positive for CK and p16, a tumor suppressor protein that is aberrantly overexpressed in HPV-infected cells. 2 questions:

1) why would overexpression of a tumor suppressor gene be associated with any cancer?

2) if p16 is normally found in cells, how would a (+) stain help at all?

anyone with experience interpreting p16 stain that can help?

thanks in advance!

1. Because the cell is making more of it than usual.

2. See #1.

 

[MirkoCrocop]

1. Because the cell is making more of it than usual.

2. See #1.

OK, so there's "overexpression" of p16 because it's uncontrolled growth, thus overexpression of most everything in the cell, whether it be tumor suppressor genes or whatever. I guess I can go along with that.

So you're saying when you're interpreting a p16 stain, the intensity of the staining is significant, almost like Her2neu?

 

[TMZ2007]

I've been wondering the same thing for a while now.

http://www.mtm-laboratories.com/us/index.php/science-a-technology/p16ink4a.html

Granted this is from a lab selling p16 detection kits, but it does sum up the rationale for testing. It seems p16 is a surrogate for infection by high-risk HPV. Viral E7 gene product dysregulates pRB, which then leads to excess p16 production. Why the excess p16 does not work downstream to shut off the cell cycle (by inhibiting CDK4) is not immediately obvious (to me).

 

[SaltySqueegee]

OK, so there's "overexpression" of p16 because it's uncontrolled growth, thus overexpression of most everything in the cell, whether it be tumor suppressor genes or whatever. I guess I can go along with that.

So you're saying when you're interpreting a p16 stain, the intensity of the staining is significant, almost like Her2neu?

I think it has a lot to do with feedback loops. The natural feedback for p16 to keep uncontrolled cdk4 activation in check may have something to do with it. We see this in cdk4 overexpressing cells frequently. Despite this pathway being intact, numerous other cell-cycle regulatory pathways are probably perturbed.

 

[sleeping beauty]

all above posts are right. E2Fs have a lot of target genes and p16 is one of them. in normal cells you can consider upregulation of p16 as a negative check. in tumor cells, it is a by product.

HPV infection certainly leads to upregulation of p16. however, upregulation of p16 may not be related to HPV infection. the upregulation of p16 is common in many cancers including basaloid/non-keratinizing scc in non-gyn systems.