SIRT-1 Over-Expression and Its Association with p16INK4a in Cervical Intraepithelial Lesions
Xiaohong Wang, Fleurette Abreo, Songlin Zhang. Louisiana State University Health Science Center, Shreveport, LA
Background: Epigenetic modifications of proteins, histones, and chromatin play an important role in relating gene expression, cancer formation, and life span. Recent evidence indicated that epigenetic changes might 'addict' cancer cells to altered signaling during the early stages of tumor development. SIRT1 plays a significant role in epigenetic modifications and is significantly elevated in many cancers. HPV E7 has been shown to up-regulate SIRT1 levels in cervical cancer cell lines, but the expression of SIRT1 in cervical intraepithelial lesions (CIN) is unknown. P16INK4a has been shown to be a very sensitive surrogate marker for hrHPV infection in CIN, so we studied the correlation between SIRT1 and p16INK4a.
Design: 77 cases (58 cervical biopsies and 19 LEEP) were selected including 29 CIN1, 32 CIN2 and 16 CIN3. All H&E slides were reviewed and the CIN diagnoses were confirmed. SIRT1 and p16 IHC were performed, and the non-lesion tissue on LEEP specimens was served as the normal controls. The staining intensity and location of SIRT1 and p16 were correlated. Fisher exact test was used for the statistic analysis.
Results: Normal cervical tissue was negative for SIRT1 except for weak positive in the basal layer. Over-expression of SIRT1 was found in 13.8% CIN 1 (4/29), 40.6% CIN2 (13/32), and 50% CIN3 (8/16), and it was statistically significant between CIN1 and CIN2/3 lesions (p=0.01). Strong diffuse p16 positive was observed in 20.6% CIN1 (6/29), 81.2% CIN2 (26/32), and 100% CIN3 (16/16) (CIN1 vs CIN2/3, p=0.0001). 22/25 cases with over-expression of SIRT1 were correlated and colocalized with p16INK4a (88%). The 3 cases with over-expression SIRT-1 and negative p16 were 2 CIN1 and 1 CIN2 cases.
Conclusions: Over-expression of SIRT1 was observed in many CIN2/3 and few CIN1 lesions and it was correlated and colocalized with p16INK4a. This is the first study to show the up-regulation of SIRT1 in CIN, and the meaning of SIRT1 over-expression found only in some CIN 2/3 lesions is not clear so far. It is possible that SIRT1 over-expression may predict the disease progression. Future study including microinvasive and invasive cervical cancers may provide some useful information. Additionally, our data did support the current concept that p16 is a sensitive biomarker in the diagnosis of high-grade CIN.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 46, Tuesday Morning