title: The utility of p16INK4a and Ki-67 staining on cell blocks prepared from residual thin-layer cervicovaginal material.
abstract: BACKGROUND
  Cell blocks can be prepared from residual thin-layer cervicovaginal (ThinPrep) material and can be used in immunohistochemical staining assays for p16INK4a and Ki-67, which are surrogate markers related to human papillomavirus infection and cell proliferation, respectively. The objectives of the current study were 1) to investigate the feasibility and the role of cell block preparations in identifying significant neoplastic and preneoplastic lesions of the uterine cervix and 2) to assess the feasibility of using p16INK4a and Ki-67 immunohistochemical staining patterns on cell blocks to identify significant preneoplastic cervical lesions.
  
  
  METHODS
  Cervicovaginal cytology specimens from 85 patients were analyzed. Cytologic diagnoses based on ThinPrep Papanicolaou test results were as follows: squamous cell carcinoma was diagnosed in 3 specimens, high-grade squamous intraepithelial lesions (HSIL) were diagnosed in 27 specimens, low-grade squamous intraepithelial lesions (LSIL) were diagnosed in 20 specimens, and atypical squamous cells of uncertain significance (ASCUS) were diagnosed in 11 specimens. Diagnoses of negativity for intraepithelial lesions or malignancy (NILM) were made in 24 specimens. Cell block sections were stained with hematoxylin and eosin and were immunostained with antibodies against p16INK4a protein and Ki-67 antigen.
  
  
  RESULTS
  The cytomorphologic diagnoses made using cell block preparations were as follows: SCC in 2 specimens, HSIL in 20 specimens, LSIL in 30 specimens, NILM in 32 specimens, and no diagnosis in 1 specimen. In 62 cases (73%), the diagnoses made using cell block preparations were in agreement with the ThinPrep diagnoses. Immunostaining of cell blocks for p16INK4a and Ki-67 exhibited a statistically significant association (P < 0.05) with the presence of significant lesions on either cell block or ThinPrep analysis.
  
  
  CONCLUSIONS
  To the authors' knowledge, p16INK4a has not been analyzed previously in ThinPrep cell blocks, and the correlation between Ki-67 expression and cell block diagnoses also has not been reported previously. The current results indicate that cell blocks prepared from residual ThinPrep material represent an additional reliable diagnostic tool in the evaluation of cervical samples. Furthermore, immunohistochemical studies may be helpful in differentiating significant preneoplastic changes from other cervical lesions, such as atrophy.
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Ilkser
authors.initials: I
authors.lastname: Akpolat
authors.forename: Debora A
authors.initials: DA
authors.lastname: Smith
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Ramzy
authors.forename: Minni
authors.initials: M
authors.lastname: Chirala
authors.forename: Dina R
authors.initials: DR
authors.lastname: Mody
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004801:Eosine Yellowish-(YS); D005240:Feasibility Studies; D005260:Female; D006416:Hematoxylin; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen; D008875:Middle Aged; D065006:Papanicolaou Test; D013048:Specimen Handling; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin