title: SIRT1 overexpression in cervical squamous intraepithelial lesions and invasive squamous cell carcinoma.
abstract: Invasive squamous cell carcinoma (SCC) of the cervix involves the progression of premalignant cervical intraepithelial neoplasia (CIN) and is associated with persistent human papillomavirus infection. Most CINs will regress, and the challenge is to identify the lesions likely to progress to invasive cancer. We evaluated Sirtuin 1 (SIRT1) expression in nonneoplastic cervix, CINs, and SCCs as a potential biomarker to predict disease progression. A total of 101 cases were selected including 29 CIN 1s, 32 CIN 2s, 16 CIN 3s, 2 microinvasive SCCs, and 22 invasive SCCs. Cervical nonneoplastic squamous epithelium showed weak positivity of SIRT1 in the basal layer. SIRT1 cytoplasmic overexpression was found in 13.8% of CIN 1s (4/29), 40.6% of CIN 2s (13/32), and 50% of CIN 3s (8/16), and it was statistically significant between CIN 1 and CIN 2/3 lesions (P=.01). All 24 cases of invasive and microinvasive SCC showed SIRT1 overexpression, with 25% (6/24) showing cytoplasmic staining only, 4.2% (1/24) showing nuclear staining only, and 70.8% (17/24) showing both nuclear and cytoplasmic staining. From CIN 1 to SCC, SIRT1 expression showed steady and statistically significant increase (CIN 1 versus CIN 2-3, P=.01; CIN 2-3 versus SCC, P=.0001). Thus, SIRT1 may serve as a potential biomarker for predicting the progression of CIN to invasive SCC.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030.
authors.forename: Anneliese
authors.initials: A
authors.lastname: Velez-Perez
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030.
authors.forename: Xiaohong I
authors.initials: XI
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030. Electronic address: Songlin.Zhang@uth.tmc.edu.
authors.forename: Songlin
authors.initials: S
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008145:Louisiana; D009361:Neoplasm Invasiveness; D030361:Papillomavirus Infections / Q000201:enzymology / Q000473:pathology / Q000821:virology; D056564:Sirtuin 1 / Q000032:analysis*; D013781:Texas; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000201:enzymology* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Biomarkers; Cervical intraepithelial neoplasia (CIN); Human papilloma virus; Sirtuin 1 (SIRT1); Squamous cell carcinoma (SCC)