title: p16INK4A expression is frequently increased in periorbital and ocular squamous lesions.
abstract: BACKGROUND
  p16 expression is a well established biomarker of cervical dysplasia and carcinoma arising from high risk human papilloma virus infection. Increased p16 expression is also seen in squamous neoplasms arising at other sites, including head, neck, and oropharyngeal tract. Squamous lesions are also frequently encountered at ocular surface and peri-orbital skin sites, but the prevalence of increased p16 expression in these lesions has been poorly studied.
  
  
  METHODS
  We retrospectively surveyed 13 ocular surface and 16 orbital squamous lesions biopsied at UC San Diego Healthcare System and VA San Diego Healthcare System for p16 expression by immunohistochemistry. These cases included ocular surface lesions with diagnoses of conjunctival intraepithelial neoplasm (CIN) and squamous cell carcinoma in situ. Peri-orbital eyelid biopsies included lesions with diagnoses of SCCis and invasive squamous cell carcinoma. We performed multivariate logistic regression, followed by student's T-test or Fisher's exact test to determine if there were statistically significant associations between p16 immunoreactivity and patient age, gender, diagnosis, and ethnicity. Statistical significance was defined as p < 0.05.
  
  
  RESULTS
  We found an unexpectedly large prevalence of strong nuclear and cytoplasmic p16 immunoreactivity in our cases. Almost all of the ocular surface squamous lesions were diffusely positive for p16 expression (12/13). All of the periorbital lesions showed diffuse p16 immunoreactivity (16/16). Altogether, 28/29 lesions tested showed strong and diffuse p16 expression. We found no statistically significant correlation between p16 expression and patient age, gender, ethnicity, or diagnosis. In 6 of the peri-orbital biopsies, we had sufficient tissue to assess high-risk HPV expression by in situ hybridization. Interestingly, all of these cases were negative for HPV, despite strong p16 expression.
  
  
  CONCLUSIONS
  Strong p16 expression was observed in virtually all of the ocular surface and peri-orbital squamous neoplasms in our study. The relationship between p16 expression and HPV infection in ocular surface and peri-orbital sites requires further investigation.
authors.affiliation: Department of Pathology, University of California San Diego and VA San Diego Healthcare System, San Diego, CA, USA. pkobalka@ucsd.edu.|Department of Pathology, School of Medicine, UC San Diego, 9500 Gilman Dr., La Jolla, CA, 92093-0612, USA. pkobalka@ucsd.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kobalka
authors.affiliation: Shiley Eye Center and Department of Ophthalmology, University of California San Diego and VA San Diego Healthcare System, San Diego, CA, USA. jabboud@ucsd.edu.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Abboud
authors.affiliation: Department of Pathology, University of California San Diego and VA San Diego Healthcare System, San Diego, CA, USA. x1liao@ucsd.edu.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liao
authors.affiliation: Department of Pathology, University of California San Diego and VA San Diego Healthcare System, San Diego, CA, USA. kaj014@ucsd.ed.
authors.forename: Karra
authors.initials: K
authors.lastname: Jones
authors.affiliation: Shiley Eye Center and Department of Ophthalmology, University of California San Diego and VA San Diego Healthcare System, San Diego, CA, USA. bwl010@ucsd.edu.
authors.forename: Bradford W
authors.initials: BW
authors.lastname: Lee
authors.affiliation: Shiley Eye Center and Department of Ophthalmology, University of California San Diego and VA San Diego Healthcare System, San Diego, CA, USA. bkorn@ucsd.edu.
authors.forename: Bobby S
authors.initials: BS
authors.lastname: Korn
authors.affiliation: Shiley Eye Center and Department of Ophthalmology, University of California San Diego and VA San Diego Healthcare System, San Diego, CA, USA. dkikkawa@ucsd.edu.
authors.forename: Don O
authors.initials: DO
authors.lastname: Kikkawa
authors.affiliation: Department of Pathology, University of California San Diego and VA San Diego Healthcare System, San Diego, CA, USA. jlin@ucsd.edu.|Shiley Eye Center and Department of Ophthalmology, University of California San Diego and VA San Diego Healthcare System, San Diego, CA, USA. jlin@ucsd.edu.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D005134:Eye Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D019942:Genes, p16 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor