Abstract

DO.24.01

Expression of p16 in conjunctival intraepithelial neoplasia and squamous cell carcinoma: is there a correlation to HPV infection?

Auw-Haedrich C.¹, Martin G.¹, Spelsberg H.², Sundmacher R.², Freudenberg N.³, Maier P.¹, Reinhard T.^1
1Universitäts-Augenklinik Freiburg; ²Universitäts-Augenklinik Düsseldorf; ³Institut für Pathologie, Freiburg

Objective: p16 INK4a is a tumor-supressor protein and a key regulator of the cell cycle functioning as a cyclin-dependent kinase inhibitor, which is intensely expressed by the neoplastic cervical epithelium (squamous and cylindric). It has been shown that the expression of p16ink4a in the squamous cervical cancer was induced by HPV. The aim of our study was to reveal the frequency of expression of p16INK4a and of HPV in different grades of conjunctival intraepithelial neoplasia.
Methods: 12 conjunctival specimens which were excised with the suspicion of conjunctival intraepithelial neoplasia (CIN), were diagnosed histologically as follows: 2 CIN grade I, 3 CIN grade II, 5 CIN grade III, 2 early invasive carcinomas under CIN III lesions. Fourteen microscopically normal postmortem conjunctival specimens, 1 slightly inflamed “normal” conjunctival specimen and 12 CIN specimens were stained immunohistochemically with antibodies against p16INK4a Ab-4 and MIB1. At least 500 cells per specimen were counted and the percentage of positively stained cells of each antibody was calculated. The presence of HPV (human papilloma virus) was examined by PCR.
Results: The expression of p16 as well as of MIB1 was significantly elevated in all cell layers of CIN and those with beginning invasion compared to control specimens (p<0.01), nevertheless without correlation to the differentiation grade of the specimens. Interestingly few control specimens also showed significantly higher expression of p16 INK4a but not of MIB1. Only two cases with CIN grade 3 contained HPV 16, all control specimens were negative for HPV genome.
Conclusions: p16 INK4a is significantly elevated in CIN compared to control specimens, nevertheless no correlation to the differentiation grade was found. Since few of the control specimens also showed increased p16INK4a expression it is not suitable as a marker for the exact determination of CIN lesions. At least in our study p16INK4a elevation is not associated with HPV infection in most of the cases.

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