Anna M Stagner1, Amir H Afrogheh2, Frederick A Jakobiec3, Codrin E Iacob4, Hans E Grossniklaus5, Vikram Deshpande6, Christopher Maske7, Donovan C Hiss8, William C Faquin6. 1. David G. Cogan Ophthalmic Pathology Laboratory, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. 2. Department of Oral and Maxillofacial Pathology, University of the Western Cape and NHLS, Cape Town, South Africa. 3. David G. Cogan Ophthalmic Pathology Laboratory, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. Electronic address: Fred_Jakobiec@meei.harvard.edu. 4. Department of Pathology, The New York Eye & Ear Infirmary of Mount Sinai, New York, New York. 5. Department of Ophthalmology, Emory University, Atlanta, Georgia. 6. Department of Pathology, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts. 7. Molecular Pathology Laboratory, Lancet Laboratories, Johannesburg, South Africa. 8. Department of Medical Biosciences, University of the Western Cape, Cape Town, South Africa.
Abstract
PURPOSE: To evaluate the role of high-risk human papillomavirus (HR-HPV) infection in periocular sebaceous carcinoma (SC) using multiple methods of detection, and to determine whether p16 overexpression is present and can be used as a surrogate marker for HR-HPV. DESIGN: Retrospective observational case series with laboratory investigations. METHODS: Unstained paraffin sections of 35 cases of periocular SC were analyzed with immunohistochemistry for p16 and subjected to polymerase chain reaction (PCR) for HR-HPV. A subset of 18 lesions that were p16-positive was further studied with a novel method of mRNA in situ hybridization (ISH) for the detection of transcriptionally active HR-HPV, an advanced technique with an enhanced sensitivity and specificity. RESULTS: The clinical findings were in keeping with those of comparable earlier studies. Strong immunohistochemical p16 positivity (meeting the criterion of >70% nuclear and cytoplasmic staining) was present in 29 of 35 cases of periocular SC (82.9%). The selected 18 p16-positive cases tested were negative for HR-HPV using mRNA ISH. PCR yielded unequivocal results with adequate DNA isolated in 24 cases, 23 of which were negative for HR-HPV. One case was positive for HPV type 16, which was found to be a false positive as collaterally determined by mRNA ISH negativity. CONCLUSION: No evidence was found for HR-HPV as an etiologic agent in the development of periocular SC using multiple modalities to maximize sensitivity and specificity and reduce the limitations of any single test. p16 overexpression is common in periocular SC but unrelated to HR-HPV status. Although p16 may be used as a surrogate marker for HR-HPV status in other tissue sites, this interpretation of p16 positivity is not applicable to periocular SC.
PURPOSE: To evaluate the role of high-risk human papillomavirus (HR-HPV) infection in periocular sebaceous carcinoma (SC) using multiple methods of detection, and to determine whether p16 overexpression is present and can be used as a surrogate marker for HR-HPV. DESIGN: Retrospective observational case series with laboratory investigations. METHODS: Unstained paraffin sections of 35 cases of periocular SC were analyzed with immunohistochemistry for p16 and subjected to polymerase chain reaction (PCR) for HR-HPV. A subset of 18 lesions that were p16-positive was further studied with a novel method of mRNA in situ hybridization (ISH) for the detection of transcriptionally active HR-HPV, an advanced technique with an enhanced sensitivity and specificity. RESULTS: The clinical findings were in keeping with those of comparable earlier studies. Strong immunohistochemical p16 positivity (meeting the criterion of >70% nuclear and cytoplasmic staining) was present in 29 of 35 cases of periocular SC (82.9%). The selected 18 p16-positive cases tested were negative for HR-HPV using mRNA ISH. PCR yielded unequivocal results with adequate DNA isolated in 24 cases, 23 of which were negative for HR-HPV. One case was positive for HPV type 16, which was found to be a false positive as collaterally determined by mRNA ISH negativity. CONCLUSION: No evidence was found for HR-HPV as an etiologic agent in the development of periocular SC using multiple modalities to maximize sensitivity and specificity and reduce the limitations of any single test. p16 overexpression is common in periocular SC but unrelated to HR-HPV status. Although p16 may be used as a surrogate marker for HR-HPV status in other tissue sites, this interpretation of p16 positivity is not applicable to periocular SC.
Authors: Michael R Sargen; Gabriel J Starrett; Eric A Engels; Elizabeth K Cahoon; Margaret A Tucker; Alisa M Goldstein Journal: Clin Cancer Res Date: 2020-09-09 Impact factor: 13.801