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Difference between revisions of "P16"
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{{ Infobox immunostain | |||
| Name = {{PAGENAME}} | |||
| Image = High grade squamous intraepithelial lesion - 2 - p16 -- high mag.jpg | |||
| Width = | |||
| Caption = [[HSIL]] showing the characteristic p16 staining. (WC/Nephron) | |||
| Abbrev = | |||
| Synonyms = | |||
| Similar = [[HPV]] | |||
| Clones = | |||
| Use = [[HSIL]] versus [[LSIL]], HPV associated SCC versus non-HPV associated SCC | |||
| Subspecial = [[gynecologic pathology]], [[head and neck pathology]] | |||
| Pattern = nuclear and cytoplasmic | |||
| Positive = endometrial tubal metaplasia, [[cervical SCC]], [[HPV-associated head and neck SCC]], [[serous carcinoma of the endometrium]] | |||
| Negative = | |||
| Other = | |||
}} | |||
[[Image:Endocervical adenocarcinoma in situ - p16 --- high mag.jpg|thumb|right|250px|[[Endocervical AIS]] showing the characteristic p16 staining.]] | |||
'''p16''' is a commonly used [[immunostain]]. It can be considered a surrogate marker for [[HPV]] infection. | '''p16''' is a commonly used [[immunostain]]. It can be considered a surrogate marker for [[HPV]] infection. | ||
p16, like most other "p" stains, is a nuclear stain. | p16, like most other "p" stains, is a nuclear stain. The antibody target is a cell cycle protein, cyclin-dependent kinase inhibitor 2A, sometimes denoted p16<sup>INK4a</sup>. | ||
==Pattern== | ==Pattern== | ||
| Line 7: | Line 23: | ||
==Use== | ==Use== | ||
*Squamous lesions of the [[uterine cervix]]. | *Squamous lesions of the [[uterine cervix]] - see [[HSIL]]. | ||
*Head and neck squamous cell carcinoma, specifically ''[[human papillomavirus-associated head and neck squamous cell carcinoma]]''. | *Head and neck squamous cell carcinoma, specifically ''[[human papillomavirus-associated head and neck squamous cell carcinoma]]''. | ||
*Increased expression in well-differentiated liposarcoma.<ref>{{Cite journal | last1 = Thway | first1 = K. | last2 = Flora | first2 = R. | last3 = Shah | first3 = C. | last4 = Olmos | first4 = D. | last5 = Fisher | first5 = C. | title = Diagnostic utility of p16, CDK4, and MDM2 as an immunohistochemical panel in distinguishing well-differentiated and dedifferentiated liposarcomas from other adipocytic tumors. | journal = Am J Surg Pathol | volume = 36 | issue = 3 | pages = 462-9 | month = Mar | year = 2012 | doi = 10.1097/PAS.0b013e3182417330 | PMID = 22301498 }}</ref> | |||
*Limited use in melanocytic lesions.<ref>{{Cite journal | last1 = Koh | first1 = SS. | last2 = Cassarino | first2 = DS. | title = Immunohistochemical Expression of p16 in Melanocytic Lesions: An Updated Review and Meta-analysis. | journal = Arch Pathol Lab Med | volume = 142 | issue = 7 | pages = 815-828 | month = Jul | year = 2018 | doi = 10.5858/arpa.2017-0435-RA | PMID = 29939777 }}</ref> | |||
===Head and neck squamous cell carcinoma=== | |||
p16 testing is useful in: | |||
#[[Lymph node metastases]] with an [[unknown primary]] - positivity suggests an oropharyngeal primary. | |||
#Oropharyngeal carcinomas. | |||
Note: | |||
*Like elsewhere, i.e. other anatomical sites, p16 is an imperfect surrogate marker for the presence of ''[[HPV]]''.<ref name=pmid23935769/> | |||
*Non-oropharyngeal sites ([[oral cavity]], [[larynx]], and hypopharynx) are not well-studied; however, it is known that p16 positivity is much less common in there.<ref name=pmid23935769>{{Cite journal | last1 = Stephen | first1 = JK. | last2 = Divine | first2 = G. | last3 = Chen | first3 = KM. | last4 = Chitale | first4 = D. | last5 = Havard | first5 = S. | last6 = Worsham | first6 = MJ. | title = Significance of p16 in Site-specific HPV Positive and HPV Negative Head and Neck Squamous Cell Carcinoma. | journal = Cancer Clin Oncol | volume = 2 | issue = 1 | pages = 51-61 | month = | year = 2013 | doi = 10.5539/cco.v2n1p51 | PMID = 23935769 }}</ref> | |||
====Images==== | |||
<gallery> | |||
Image:Consistent with HPV-associated SCC - p16 -- intermed mag.jpg | c/w HPV-assoc. SCC - p16 - intermed. mag. (WC/Nephron) | |||
Image:Consistent with HPV-associated SCC - p16 -- high mag.jpg | c/w HPV-assoc. SCC - p16 - high mag. (WC/Nephron) | |||
</gallery> | |||
===Penile cancer=== | |||
*p16 is considered surrogate for HPV and ''block-type positivity'' is considered indicative of HPV.<ref name=pmid36221864>{{cite journal |authors=Menon S, Moch H, Berney DM, Cree IA, Srigley JR, Tsuzuki T, Compérat E, Hartmann A, Netto G, Rubin MA, Gill AJ, Turajlic S, Tan PH, Raspollini MR, Tickoo SK, Amin MB |title=WHO 2022 classification of penile and scrotal cancers: updates and evolution |journal=Histopathology |volume=82 |issue=4 |pages=508–520 |date=March 2023 |pmid=36221864 |doi=10.1111/his.14824 |url=}}</ref> | |||
**A meta-analysis from 2018 shows that various p16 staining criteria have been used in the past.<ref name=pmid29987099>{{cite journal |authors=Sand FL, Rasmussen CL, Frederiksen MH, Andersen KK, Kjaer SK |title=Prognostic Significance of HPV and p16 Status in Men Diagnosed with Penile Cancer: A Systematic Review and Meta-analysis |journal=Cancer Epidemiol Biomarkers Prev |volume=27 |issue=10 |pages=1123–1132 |date=October 2018 |pmid=29987099 |doi=10.1158/1055-9965.EPI-18-0322 |url=}}</ref> | |||
<pre> | |||
The p16 staining is patchy (~10% of tumour) and moderate. The 2022 WHO Classification describes "block-type positivity" as being relevant; as such, the case is interpreted as p16 NEGATIVE. | |||
HPV testing will be requested and the findings reported in an addendum. | |||
</pre> | |||
==Positive== | |||
*[[Squamous cell carcinoma]] - esp. [[cervical SCC]], anal SCC, penile SCC, [[HPV-associated head and neck SCC]]. | |||
*High grade [[urothelial carcinoma]] ~86% of cases by PCR.<ref name=pmid25069600>{{Cite journal | last1 = Piaton | first1 = E. | last2 = Casalegno | first2 = JS. | last3 = Advenier | first3 = AS. | last4 = Decaussin-Petrucci | first4 = M. | last5 = Mege-Lechevallier | first5 = F. | last6 = Ruffion | first6 = A. | last7 = Mekki | first7 = Y. | title = p16(INK4a) overexpression is not linked to oncogenic human papillomaviruses in patients with high-grade urothelial cancer cells. | journal = Cancer Cytopathol | volume = 122 | issue = 10 | pages = 760-9 | month = Oct | year = 2014 | doi = 10.1002/cncy.21462 | PMID = 25069600 }}</ref> | |||
*[[Serous carcinoma of the endometrium]] - should be strong.<ref name=pmid17581420>{{Cite journal | last1 = Chiesa-Vottero | first1 = AG. | last2 = Malpica | first2 = A. | last3 = Deavers | first3 = MT. | last4 = Broaddus | first4 = R. | last5 = Nuovo | first5 = GJ. | last6 = Silva | first6 = EG. | title = Immunohistochemical overexpression of p16 and p53 in uterine serous carcinoma and ovarian high-grade serous carcinoma. | journal = Int J Gynecol Pathol | volume = 26 | issue = 3 | pages = 328-33 | month = Jul | year = 2007 | doi = 10.1097/01.pgp.0000235065.31301.3e | PMID = 17581420 }}</ref> | |||
*[[High-grade squamous intraepithelial lesion]] - full thickness, strong. | |||
**A subset of LSIL stains with p16; however, it is ''not'' full thickness - see ''[[HSIL]]'' article. | |||
*[[Small cell carcinoma of the lung]] - most cases (95 of 101 cases in one series<ref name=pmid29566943>{{cite journal |authors=Švajdler M, Mezencev R, Ondič O, Šašková B, Mukenšnábl P, Michal M |title=P16 is a useful supplemental diagnostic marker of pulmonary small cell carcinoma in small biopsies and cytology specimens |journal=Ann Diagn Pathol |volume=33 |issue= |pages=23–29 |date=April 2018 |pmid=29566943 |doi=10.1016/j.anndiagpath.2017.11.008 |url=}}</ref>). | |||
Note: | |||
*Positive staining (in the head and neck pathology context) is defined as (strong block) positive staining in >75% (or >50%) of lesional cells.<ref name=pmid28621317>{{cite journal |authors=Shelton J, Purgina BM, Cipriani NA, Dupont WD, Plummer D, Lewis JS |title=p16 immunohistochemistry in oropharyngeal squamous cell carcinoma: a comparison of antibody clones using patient outcomes and high-risk human papillomavirus RNA status |journal=Mod Pathol |volume=30 |issue=9 |pages=1194–1203 |date=September 2017 |pmid=28621317 |doi=10.1038/modpathol.2017.31 |url=}}</ref> | |||
**Staining varies somewhat by the p16 clone used. | |||
===Benign=== | |||
*p16 endometrial tubal metaplasia.<ref name=pmid17429140>{{Cite journal | last1 = Horree | first1 = N. | last2 = Heintz | first2 = AP. | last3 = Sie-Go | first3 = DM. | last4 = van Diest | first4 = PJ. | title = p16 is consistently expressed in endometrial tubal metaplasia. | journal = Cell Oncol | volume = 29 | issue = 1 | pages = 37-45 | month = | year = 2007 | doi = | PMID = 17429140 }}</ref> | |||
====Focal staining==== | |||
*[[Endometriosis]] - focal/weak staining may be seen.<ref name=pmid26095917>{{Cite journal | last1 = Stewart | first1 = CJ. | last2 = Bharat | first2 = C. | title = Clinicopathological and immunohistological features of polypoid endometriosis. | journal = Histopathology | volume = 68 | issue = 3 | pages = 398-404 | month = Feb | year = 2016 | doi = 10.1111/his.12755 | PMID = 26095917 }}</ref><ref name=pmid16462152>{{Cite journal | last1 = O'Neill | first1 = CJ. | last2 = McCluggage | first2 = WG. | title = p16 expression in the female genital tract and its value in diagnosis. | journal = Adv Anat Pathol | volume = 13 | issue = 1 | pages = 8-15 | month = Jan | year = 2006 | doi = 10.1097/01.pap.0000201828.92719.f3 | PMID = 16462152 }}</ref> | |||
==Negative== | |||
<!-- *Breast carcinoma. --> | |||
<!-- *[[Prostate carcinoma]]. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267667/ --> | |||
*[[Lung squamous cell carcinoma]]<ref name=pmid20823766>{{Cite journal | last1 = Pereira | first1 = TC. | last2 = Share | first2 = SM. | last3 = Magalhães | first3 = AV. | last4 = Silverman | first4 = JF. | title = Can we tell the site of origin of metastatic squamous cell carcinoma? An immunohistochemical tissue microarray study of 194 cases. | journal = Appl Immunohistochem Mol Morphol | volume = 19 | issue = 1 | pages = 10-4 | month = Jan | year = 2011 | doi = 10.1097/PAI.0b013e3181ecaf1c | PMID = 20823766 }}</ref> - 21% positive (7/33).<ref name=pmid19369633>{{Cite journal | last1 = Wang | first1 = CW. | last2 = Wu | first2 = TI. | last3 = Yu | first3 = CT. | last4 = Wu | first4 = YC. | last5 = Teng | first5 = YH. | last6 = Chin | first6 = SY. | last7 = Lai | first7 = CH. | last8 = Chen | first8 = TC. | title = Usefulness of p16 for differentiating primary pulmonary squamous cell carcinoma from cervical squamous cell carcinoma metastatic to the lung. | journal = Am J Clin Pathol | volume = 131 | issue = 5 | pages = 715-22 | month = May | year = 2009 | doi = 10.1309/AJCPTPBC6V5KUITM | PMID = 19369633 }}</ref> | |||
==References== | |||
{{Reflist|1}} | |||
==External links== | ==External links== | ||
*[http://www.mtmlabs.com/us/index.php?option=com_content&view=article&id=107&Itemid=11 Interpretation of p16 (mtmlabs.com)]. | *[http://www.mtmlabs.com/us/index.php?option=com_content&view=article&id=107&Itemid=11 Interpretation of p16 (mtmlabs.com)]. | ||
[[Category: | [[Category:Immunohistochemistry]] | ||