Kotelnikov V M, Coon J S, Mundle S, Kelanic S, LaFollette S, Taylor S I V, Hutchinson J, Panje W, Caldarelli D D, Preisler H D
Rush Cancer Institute, Department of Pathology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3833, USA.
Clin Cancer Res. 1997 Jan;3(1):95-101.
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 in 46 SCCHNs using immunohistochemistry. Before biopsy, the patients received an in vivo infusion of iododeoxyuridine (IdUrd) for cell proliferation 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 tumors 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 tumors studied. ISEL-positive tumors contained a significantly higher proportion 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 noninvolved oral mucosa, cD1(+) cells were located primarily in the suprabasal 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 percentage of cD1(+) cells in the oral epithelium from nontumor controls (uvula samples) was significantly higher than in the SCCHN group in both 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 distributed evenly along the epithelial lining, in SCCHN samples the regions showing cD1 expression alternated with areas in which cD1 expression was undetectable. These data indicate that cD1 expression in SCCHN varies among tumors and is not correlated with cell proliferation. In noninvolved oral mucosa, cD1 expression differs from that in truly normal epithelium obtained from nontumor patients. A correlation between cD1 expression and the extent of ISEL positivity suggests a possible involvement of cD1 expression in the apoptotic pathways.
细胞周期调节因子细胞周期蛋白D1（cD1）表达失调可能是头颈部鳞状细胞癌（SCCHN）快速增殖的原因。我们运用免疫组织化学方法研究了46例SCCHN中cD1的表达情况。活检前，患者接受碘脱氧尿苷（IdUrd）体内输注以评估细胞增殖情况。此外，采用原位末端标记法（ISEL）评估凋亡水平。在33例肿瘤中，cD1（+）细胞比例为0.5%至51.3%（19.9±2.2%）。13例肿瘤未表达cD1。cD1（+）肿瘤中S期（IdUrd阳性）细胞比例为26.3±1.8%，而cD1（-）肿瘤中为20.0±2.4%（P = 0.06）。cD1（+）细胞百分比与S期细胞百分比无相关性（P = 0.37）。在所研究的33例肿瘤中，有15例通过ISEL检测到凋亡。ISEL阳性肿瘤中cD1（+）细胞比例（14.9±2.6%）显著高于cD1（-）肿瘤（7.9±2.8%；P = 0.03）。cD1（+）细胞百分比与ISEL程度呈正相关（r = 0.54；P < 0.001）。在未受累的口腔黏膜中，cD1（+）细胞主要位于基底上层（29.3±3.8%，而基底层为1.2±0.2%）。44例黏膜标本中只有23例含有cD1（+）细胞。所有cD1（-）样本均有增殖活性且含有IdUrd标记细胞。非肿瘤对照（悬雍垂样本）口腔上皮中cD1（+）细胞在基底层（2.4±0.4%；P = 0.008）和基底上层（42.7±3.3%；P = 0.005）的百分比均显著高于SCCHN组。此外，在悬雍垂中，cD1（+）细胞沿上皮衬里均匀分布，而在SCCHN样本中，显示cD1表达的区域与检测不到cD1表达的区域交替出现。这些数据表明，SCCHN中cD1表达在肿瘤之间存在差异，且与细胞增殖无关。在未受累的口腔黏膜中，cD1表达与从非肿瘤患者获得的真正正常上皮不同。cD1表达与ISEL阳性程度之间的相关性表明cD1表达可能参与凋亡途径。
