title: Usefulness of p16ink4a, ProEX C, and Ki-67 for the diagnosis of glandular dysplasia and adenocarcinoma of the cervix uteri.
abstract: Although the diagnostic criteria of in-situ and invasive adenocarcinomas of the cervix uteri are well established, the differentiation from benign mimics may be difficult and the morphologic features of the precursors of endocervical adenocarcinoma are still debated. In this study, we evaluated the usefulness of p16ink4a (p16), ProEX C, and Ki-67 for the diagnosis of endocervical adenocarcinoma and its precursors. Immunohistochemistry with p16, ProEX C, and Ki-67 was performed in 82 glandular lesions including 15 invasive adenocarcinomas, 29 adenocarcinomas in situ (AIS), 22 non-neoplastic samples, and 16 cases of glandular dysplasia (GD), which showed significant nuclear abnormalities but did not meet the diagnostic criteria for AIS. The immunohistochemical expression pattern was scored according to the percentage of the stained cells (0, 1+, 2+, and 3+ when 0% to 5%, 6% to 25%, 26% to 50%, and more than 50% of the cells were stained, respectively) and was evaluated for each antibody. p16 was at least focally expressed (1+ or more) in 14 of 15 invasive adenocarcinomas, in all AIS and in 7 negative samples. ProEX C and Ki-67 both scored 1+ or more in all adenocarcinomas and AIS and in 8 and 6 negative samples, respectively. Of the GD 15, 14, and 15 expressed p16, ProEX C, and Ki-67, respectively. The score differences between neoplastic and non-neoplastic samples were highly significant for each marker (P<0.001); however, the score distribution by marker differed significantly only in GD (P=0.006) in which, compared with the other markers, p16 showed more often a 3+ pattern. Our study shows that p16, Ki-67, and ProEX C may be helpful for the diagnosis of glandular lesions of the cervix uteri and may also improve the diagnostic accuracy of endocervical GD. In particularly problematic cases, the combination of p16 and a proliferation marker can provide additional help for the interpretation of these lesions.
authors.affiliation: Department of Pathology, Central Hospital Bolzano, Bolzano, Italy. ginegri@gmail.com
authors.forename: Giovanni
authors.initials: G
authors.lastname: Negri
authors.forename: Giulia
authors.initials: G
authors.lastname: Bellisano
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Carico
authors.forename: Gavino
authors.initials: G
authors.lastname: Faa
authors.forename: Armin
authors.initials: A
authors.lastname: Kasal
authors.forename: Sonia
authors.initials: S
authors.lastname: Antoniazzi
authors.forename: Eduard
authors.initials: E
authors.lastname: Egarter-Vigl
authors.forename: Andrea
authors.initials: A
authors.lastname: Piccin
authors.forename: Paolo
authors.initials: P
authors.lastname: Dalla Palma
authors.forename: Fabio
authors.initials: F
authors.lastname: Vittadello
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis*; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000032:analysis*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D064111:Minichromosome Maintenance Complex Component 2; D004250:DNA Topoisomerases, Type II