title: Cyclin D1 (PRAD1, CCND1) and glutathione-S-transferase pi gene expression in head and neck squamous cell carcinoma.
abstract: Chromosome 11q13 amplification has been identified in a subset of head and neck squamous cell carcinomas (H&N SCCs). This region contains several putative oncogenes, including cyclin D1 (PRAD1, CCND1), which encodes for an important cell cycle regulatory protein, and the locus encoding for the drug-detoxifying enzyme glutathione-S-transferase-pi (GST-pi). To determine the relationship of cyclin D1 and GST-pi gene amplification to expression of the encoded proteins, the authors examined 64 H&N SCCs by both Southern blot hybridization and immunohistochemistry, using a recently described, affinity-purified, anticyclin D1 polyclonal antibody no. 19 as well as a polyclonal antibody against GST-pi. Anticyclin D1 antibody no. 19 labeled the tumor cell nuclei in 28 (44%) of the H&N SCCs, whereas cytoplasmic immunoreactivity for GST-pi was noted in 55 (86%) neoplasms. By Southern blot 24 tumors (37.5%) showed twofold to tenfold amplification of 11q13 loci; only two of these were coamplified for GST-pi. Immunopositivity with anticyclin D1 antibody no. 19 but not anti-GST-pi significantly correlated with 11q13 amplification (P < .0001). Of the 28 tumors positive with anticyclin D1 antibody no. 19, however, only 18 (64%) were amplified for 11q13, and six amplified tumors did not react with the no. 19 antibody. A strong trend was noted between anticyclin D1 antibody no. 19 reactivity and a hypopharyngeal primary site (P = .053), but no correlations were observed between immunoreactivity and cytological grade, architectural pattern, pathological stage, and disease-free or overall survival. The inconsistent association of cyclin D1 immunoreactivity with 11q13 amplification indicates that other mechanisms may exist for protein overexpression. Immunoreactivity for the GST-pi protein is prevalent in H&N SCC but is clearly unassociated with amplification. In this series, the presence or extent of cyclin D1 and GST-pi immunoreactivity was of no proven prognostic benefit in H&N SCC.
authors.affiliation: Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gaffey
authors.forename: J C
authors.initials: JC
authors.lastname: Iezzoni
authors.forename: S D
authors.initials: SD
authors.lastname: Meredith
authors.forename: J C
authors.initials: JC
authors.lastname: Boyd
authors.forename: M H
authors.initials: MH
authors.lastname: Stoler
authors.forename: L M
authors.initials: LM
authors.lastname: Weiss
authors.forename: L R
authors.initials: LR
authors.lastname: Zukerberg
authors.forename: P A
authors.initials: PA
authors.lastname: Levine
authors.forename: A
authors.initials: A
authors.lastname: Arnold
authors.forename: M E
authors.initials: ME
authors.lastname: Williams
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D019938:Cyclin D1; D016213:Cyclins / Q000032:analysis / Q000235:genetics*; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000032:analysis / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015513:Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
chemical_list: D016213:Cyclins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D019938:Cyclin D1; D005982:Glutathione Transferase