CYCLIN D1 EXPRESSION IN SQUAMOUS-CELL CARCINOMAS OF THE HEAD AND NECKAND IN ORAL-MUCOSA IN RELATION TO PROLIFERATION AND APOPTOSIS

Deregulation of expression of the cell cycle regulator cyclin D1 (cD1) may be responsible for rapid proliferation of squamous cell carcinoma of the head and neck (SCCHN), We have studied the expression of cD1 i n 46 SCCHNs using immunohistochemistry. Before biopsy, the patients re ceived an in vivo infusion of iododeoxyuridine (IdUrd) for cell prolif eration assessment, Additionally, the level of apoptosis was estimated using in situ end labeling (ISEL), Among 33 tumors, the proportion of cD1(+) cells varied from 0.5 to 51.3% (19.9 +/- 2.2%), Thirteen tumor s did not express cD1, The fraction of S-phase (IdUrd-positive) cells was 26.3 +/- 1.8% in cD1(+) versus 20.0 +/- 2.4% in cD1(-) tumors (P = 0.06), The percentages of cD1(+) cells and of S-phase cells were not correlated (P = 0.37), Apoptosis was detected by ISEL in 15 of 33 tumo rs studied, ISEL-positive tumors contained a significantly higher prop ortion of cD1(+) cells (14.9 +/- 2.6%) than cD1(-) ones (7.9 +/- 2.8%; P = 0.03), There was a positive correlation between the percentage of cD1(+) cells and the degree of ISEL (r = 0.54; P < 0.001), In noninvo lved oral mucosa, cD1(+) cells were located primarily in the suprabasa l layers (29.3 +/- 3.8% versus 1.2 +/- 0.2% in the basal layer), Only 23 of 44 mucosal specimens contained cD1(+) cells, All cD1(-) samples were proliferatively active and contained IdUrd-labeled cells, The per centage of cD1(+) cells in the oral epithelium from nontumor controls (uvula samples) was significantly higher than in the SCCHN group in bo th basal (2.4 +/- 0.4%; P = 0.008) and suprabasal (42.7 +/- 3.3%; P = 0.005) layers, Additionally, whereas in uvuli, cD1(+) cells were distr ibuted evenly along the epithelial lining, in SCCHN samples the region s showing cD1 expression alternated with areas in which cD1 expression was undetectable, These data indicate that cD1 expression in SCCHN va ries among tumors and is not correlated with cell proliferation, In no ninvolved oral mucosa, cD1 expression differs from that in truly norma l epithelium obtained from nontumor patients, A correlation between cD 1 expression and the extent of ISEL positivity suggests a possible inv olvement of cD1 expression in the apoptotic pathways.