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p53 Expression and Relation to Human Papillomavirus Infection in Pingueculae, Pterygia, and Limbal Tumors
Nicholas Dushku, MD;
Sandra L. S. Hatcher, MSc;
Daniel M. Albert, MD;
Ted W. Reid, PhD
Arch Ophthalmol. 1999;117:1593-1599.
Background The tumor suppressor gene p53 is expressed without apoptosis in the limbal basal stem cells of all pterygia and limbal tumors and most pingueculae from which these growths seem to originate. Oncogenic human papillomaviruses (HPVs) have been found in pterygia and limbal tumors, and HPV and p53 overexpression commonly coexist in oropharyngeal and penile carcinomas.
Objective To search for HPV DNA as a cofactor in the development of pingueculae, pterygia, and limbal tumors.
Methods We examined specimens—1 of pinguecula, 13 of pterygia (7 primary, 1 recurrent, 1 with dysplasia, and 4 primary not tested for p53), and 10 of limbal tumors (2 with actinic keratosis dysplasia, 1 with conjunctival intraepithelial neoplasia, 3 with carcinoma in situ, and 4 with squamous cell carcinoma)—expressing p53. Specimens were tested for the presence of HPV DNA by the polymerase chain reaction using degenerate consensus primers for the highly conserved portion of the L1 region that encodes a capsid protein of the virus. This assay has a wide spectrum with capability of detecting essentially all known HPV types. Nested polymerase chain reaction was performed on all specimens. Primers of the cystic fibrosis gene were used to confirm the presence of genomic DNA and to rule out inhibitors. Purified HPV DNA type 11 was the positive control, and HPV-negative genomic DNA was the negative control.
Results Using consensus primers for the highly conserved portion of the L1 region, all specimens of pingueculae, pterygia, and limbal tumors studied were negative for HPV DNA by nested polymerase chain reaction.
Conclusions Human papillomavirus DNA is not required as a cofactor in the development of pterygia and limbal tumors. These data support the theory that increased p53 expression in the limbal epithelia of pingueculae, pterygia, and limbal tumors indicates the probable existence of p53 mutations in these cells as an early event in their development, which is consistent with UV irradiation causation. Thus, due to a damaged p53-dependent programmed cell death mechanism, mutations in other genes may be progressively acquired. This would allow for the multistep development of pterygia and limbal tumor cells from p53-mutated limbal epithelial basal stem cells overlying pingueculae.
From the Department of Ophthalmology, Kaiser Permanente Medical Center (Dr Dushku), and the Department of Pathology, University of California–Davis Medical Center (Ms Hatcher), Sacramento; the Department of Ophthalmology, University of Wisconsin Medical Center (Dr Albert), Madison; and the Departments of Ophthalmology and Visual Sciences and Cell Biology and Biochemistry, Texas Tech University Health Sciences Center and South West Cancer Center (Dr Reid), Lubbock.
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