title: Evaluation of p16INK4a and pRb expression in cervical squamous and glandular neoplasia.
abstract: p16(INK4a) is known to play a critical role as a negative regulator of cell cycle progression and differentiation by controlling the activity of the tumor-suppressor protein pRb. The present study evaluated the expression of p16(INK4a) and pRb in cervical squamous and glandular neoplasia. Immunohistochemical staining was performed for p16(INK4a) and pRb in formalin-fixed, paraffin-embedded tissue sections of the uterine cervix using an indirect immunoperoxidase method. p16(INK4a) staining was detected in 7 of 108 sections (6.5%) of normal squamous mucosa, in scattered ciliated columnar cells in 33 of 88 sections (37.5%) of normal endocervical glands, in 9 of 30 sections (30%) with Nabothian cysts, and in 4 of 4 areas (100%) of tubal metaplasia. In contrast, strong p16(INK4a) staining was found in 13 of 18 cases (72.2%) of cervical intraepithelial neoplasia (CIN) I and in all cases of CIN II/III (n = 46), squamous cell carcinoma (n = 18), endocervical glandular dysplasia (n = 10), adenocarcinoma in situ (n = 23), and invasive adenocarcinoma (n = 12). pRb expression was detected in each diagnostic category; however, the proportion of pRb-positive cells was relatively decreased in high-grade premalignant and malignant lesions of the squamous and endocervical mucosa and showed a generally inverse correlation with the expression of p16(INK4a) at the tissue level. These findings confirm a correlation between the expression of p16(INK4a) and pRb in cervical neoplasias and indicate that p16(INK4a) is a specific marker for premalignant and malignant lesions of the squamous and endocervical mucosa.
authors.affiliation: Department of Pathology, University of Colorado Health Sciences Center, Denver, 80262, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tringler
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Gup
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Singh
authors.forename: Steve
authors.initials: S
authors.lastname: Groshong
authors.forename: A Laurie
authors.initials: AL
authors.lastname: Shroyer
authors.forename: David E
authors.initials: DE
authors.lastname: Heinz
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Shroyer
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016160:Retinoblastoma Protein / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein