title: p16, p14, p53, and cyclin D1 expression and HPV analysis in small cell carcinomas of the uterine cervix.
abstract: Small cell carcinomas (SmCCs) of the uterine cervix are rare tumors. The knowledge regarding protein expression of several checkpoint candidates of cell cycle regulation is limited. Surgically treated SmCCs were selected from our files for immunohistochemical staining (neuroendocrine markers, p53, p16, p14, and cyclin D1). Polymerase chain reaction analysis, using general primers, was performed for human papillomavirus analysis. Nine of 677 tumors (1.3%) were classified as SmCCs after Grimelius staining (8/9 tumors positive) and immunohistochemical reaction against neurone-specific enolase, chromogranin A, synaptophysin (7/9 positive tumors), and CD 56 (8/9 positive tumors). All specimens were positive for at least two of the above. Two SmCCs were p53 positive and one case was p14 positive. Cyclin D1 staining was completely negative. All cases showed strong nuclear and/or cytoplasmic p16-immunostaining. Seven tumors represented human papillomavirus positivity for high-risk types. Four patients died of the tumor after a median time of 36.7 months (range, 15-56 months), representing a 5-year survival rate of 56%. The results suggest that p16 is up-regulated or accumulated in the SmCCs of the uterine cervix, probably caused by infection with human papillomavirus. p14 inactivation is of high prevalence in SmCCs and detection rate of p53 is similar to other histologic types of cervical carcinomas.
authors.affiliation: Institute of Pathology, Division of Gynecopathology, and Department of Obstetrics and Gynecology, University of Leipzig, Leipzig, Germany. hornl@medizin.uni-leipzig.de
authors.forename: Lars-Christian
authors.initials: LC
authors.lastname: Horn
authors.forename: Kristin
authors.initials: K
authors.lastname: Lindner
authors.forename: Grit
authors.initials: G
authors.lastname: Szepankiewicz
authors.forename: Jeanett
authors.initials: J
authors.lastname: Edelmann
authors.forename: Bettina
authors.initials: B
authors.lastname: Hentschel
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.forename: Karl
authors.initials: K
authors.lastname: Bilek
authors.forename: Uwe-Gerd
authors.initials: UG
authors.lastname: Liebert
authors.forename: Cristine E
authors.initials: CE
authors.lastname: Richter
authors.forename: Jens
authors.initials: J
authors.lastname: Einenkel
authors.forename: Cornelia
authors.initials: C
authors.lastname: Leo
mesh_terms: D000328:Adult; D018288:Carcinoma, Small Cell / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000821:virology*; D019938:Cyclin D1 / Q000032:analysis* / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D027383:Papillomaviridae / Q000502:physiology*; D030361:Papillomavirus Infections; D016133:Polymerase Chain Reaction; D015996:Survival Rate; D025803:Tumor Suppressor Protein p14ARF / Q000032:analysis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000032:analysis* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000821:virology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1