CYCLIN D1 (PRAD1, CCND1) AND GLUTATHIONE-S-TRANSFERASE-PI GENE-EXPRESSION IN HEAD AND NECK SQUAMOUS-CELL CARCINOMA

Chromosome 11q13 amplification has been identified in a subset of head and neck squamous cell carcinomas (H&N SCCs). This: region contains s everal putative oncogenes, including cyclin D1 (PRAD1, CCND1), which e ncodes for an important cell cycle regulatory protein, and the locus e ncoding for the drug-detoxifying enzyme glutathione-S-transferase-pi ( GST-pi). To determine the relationship of cyclin D1 and GST-pi gene am plification to expression of the encoded proteins, the authors examine d 64 H&N SCCs by both Southern blot hybridization and immunohistochemi stry using a recently described, affinity-purified, anticyclin D1 poly clonal antibody no. 19 as well as a polyclonal antibody against GST-pi . Anticyclin D1 antibody no. 19 labeled the tumor cell nuclei in 28 (4 4%) of the H&N SCCs, whereas cytoplasmic immunoreactivity for GST-pi w as noted in 55 (86%) neoplasms. By Southern blot 24 tumors (37.5%) sho wed twofold to tenfold amplification of 11q13 loci; only two of these were coamplified for GST-pi. Immunopositivity with anticyclin D1 antib ody no. 19 but not anti-GST-pi significantly correlated with 11q13 amp lification (P <.0001). Of the 28 tumors positive with anticyclin D1 an tibody no. 19, however, only 18 (64%) were amplified for 11q13, and si x amplified tumors did not react with the no. 19 antibody. A strong tr end was noted between anticyclin D1 antibody no. 19 reactivity and a h ypopharyngeal primary site (P =.053), but no correlations were observe d between immunoreactivity and cytological grade, architectural patter n, pathological stage, and disease-free or overall survival. The incon sistent association of cyclin D1 immunoreactivity with 11q13 amplifica tion indicates that other mechanisms may exist for protein overexpress ion; Immunoreactivity for the GST-pi protein is prevalent in H&N SCC b ut is clearly unassociated with amplification. In this series, the pre sence or extent of cyclin D1 and GST-pi immunoreactivity was of no pro ven prognostic benefit in H&N SCC. Copyright (C) 1995 by W.B. Saunders Company