Cyclin D1 (PRAD1, CCND1) and glutathione-S-transferase π 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-π (GST-π). To determine the relationship of cyclin Dl and GST-π 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 Dl polyclonal antibody no. 19 as well as a polyclonal antibody against GST-π. Anticyclin Dl antibody no. 19 labeled the tumor cell nuclei in 28 (44%) of the H&N SCCs, whereas cytoplasmic immunoreactivity for GST-π 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-π. Immunopositivity with anticyclin D1 antibody no. 19 but not anti-GST-π significantly correlated with 11q13 amplification (P < .0001). Of the 28 tumors positive with anticyclin Dl 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 Dl immunoreactivity with 11q13 amplification indicates that other mechanisms may exist for protein overexpression. Immunoreactivity for the GST-π protein is prevalent in H&N SCC but is clearly unassociated with amplification. In this series, the presence or extent of cyclin Dl and GST-π immunoreactivity was of no proven prognostic benefit in H&N SCC. © 1995.

Publication Title

Human Pathology

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