Submit processed tissue block or tissue section mounted on a charged, unstained slide
AHL - Immunohistochemistry
Days Set Up:
Mo - Fr
1 - 2 days
If requested, an interpretive report will be provided All IHC stains will include a positive control tissue
Collection/ Processing Details:
p16 (ink4) is a cell cycle associated protein which inhibits cyclin-dependent kinases by blocking substrate phosphorylation of the tumor suppressor retinoblastoma protein (Rb) and Rb related proteins p107 and p130 (thus interfering with the cell cycle)
The gene that codes for p16 (CDKN2 gene) is mutated in a high percentage of tumors (including 75% of melanomas, as well as other cancers including breast and pancreas)
The functional inactivation of p16 (as by HPV related infections in cervical lesions) is thought to lead to over-expression of this protein (and loss of its cell-cycle inhibitory effect)
Cytoplasmic, with some nuclear staining also observed
Staining in cervical neoplasia has been graded as1:
Positive - continuous staining the horizontal plane, either partial or full thickness
Focal positive - less than 80% staining in an interrupted plane
Negative - weakly diffuse staining characterized by a "blush"
P16 is a marker for high risk HPV; useful in identifying SIL associated with high-risk HPV types
Particularly useful in determining whether atypical squamous metaplasia is HSIL
Staining for p16 correlates with a positive predictive value for HPV (88.7%)
95.8% of LSIL and 92% of HSIL stain for p16 (low risk strains of HPV-related neoplasia are less likely to stain as compared to high risk strains)
Note: HPV negative carcinomas can also stain for this, indicating different pathways leading to p16 over-expression
P16 will stain tubal metaplasia
p16 will identify cervical adenocarcinoma, particularly those associated with HPV 16/18 infections
Normal epithelium is p16 negative; inflammatory and metaplastic lesions are p16 negative or will show just focal staining
Keating JT et al: Ki-67, Cyclin E and p16 are complimentary surrogate bio-markers for HPV-related cervical neoplasia. Am J Surg Pathol 25(7): 884-891, 2001.
Sano T et al: Expression status of p16 protein is associated with HPV oncogenic potential in cervical and genital lesions. Am J Pathol 1998; 153:1741-8, 1998.
Hirama T et al: p16 gene is not altered in uterine cervical carcinomas or cell lines. Mod Pathol 1996; 9:26-31.
Milde-Langosch K et al: Expression of cyclin-dependent kinase inhibitors p16 etc. in HPV positive and HPV negative cervical adenocarcinoma. Virchows Arch (2001) 439; 55-61.
Klaes R et al: Over-expression of p16 as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer: 92, 276-284 (2001).
Keating JT et al: Surrogate bio-markers of HPV infection in cervical neoplasia screening and diagnosis. Adv Anat Pathol, vol 8, no 2, 83-92, 2001.
Negri G, et al: P16 is a useful marker for the diagnosis of adenocarcinoma of the cervix uteri and its precursors; an immunohistochemical study with immunocytochemical correlations, Am J Surg Pathol 27 (2): 187-193, 2003.
Kong CS et al: p16 immunohistochemistry is superior to HPV in situ hybridization for the detection of high-risk PHPV in atypical squamous metaplasia. Am J Surg Pathol 2007; 31:33-43).