P16/MIB-1 Immunoreactivity and HPV DNA Status in Tubal Metaplasia of Endocervical Epithelium: Is There Any Correlation?
Juan C Gomez-Gelvez, Ziying Zhang, Mohammad Raoufi, Thomas E Buekers. Henry Ford Hospital, Detroit, MI
Background: Studies have shown that p16 over-expression occurs in more than half of endocervical tubal metaplasia (TM) and as a result, it is speculated that TM may be a precursor of endocervical glandular neoplasm. In addition, it has been shown that most cases of endocervical glandular neoplasm are associated with HPV infection. In this study, we evaluate p16 over-expression and HPV status in TM to investigate any correlation between these potential neoplastic markers.
Design: From June 2005 to September 2011, all cases diagnosed as AGUS on liquid based cytology with concurrent high-risk HPV DNA testing and subsequent biopsy proven TM were selected. Biopsies containing concurrent squamous dysplasia were excluded due to potential confounding by HPV positivity in dysplastic squamous epithelium. A total of 26 patients with an age range of 21-49 were identified. HPV DNA test results were collected. P16 and MIB-1 immunostains were performed on 17 cases for which the pathology materials were available. MIB-1 stain was scored as <10%, 10-30%, >30% nuclear staining. P16 stain was graded as negative, focal+ (<50% cytoplasmic and nuclear stain) and diffuse+ (>50% cytoplasmic and nuclear stain).
Results: Eight out of 17 cases were negative for p16 stain, 5/17 were focally and 4/17 were diffusely positive. Cases with negative p16 stain demonstrated minimal nuclear changes and architecturally benign endocervical glands lined by cilia. However, cases with focal or diffuse p16 positivity showed significant nuclear atypia including nuclear enlargement, hyperchromasia, and pseudostratification. In all cases, MIB-1 stain was either negative or showed <10% of nuclear staining. Of particular interest, high-risk HPV DNA test was negative in all cases.
Conclusions: This is the first study to evaluate the pattern of p16 over-expression in endocervical TM and its correlation with HPV status. The distribution and intensity of p16 over-expression in TM tended to directly correlate with the degree of nuclear atypia. More importantly, no correlation was found between p16 over-expression and HPV status in TM. The association between p16 over-expression and premalignant potential of TM warrants further investigation.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 122, Tuesday Afternoon