Spafford M F, Koeppe J, Pan Z, Archer P G, Meyers A D, Franklin W A
Department of Otolaryngology, University of Colorado Health Sciences Center, Denver, USA.
Arch Otolaryngol Head Neck Surg. 1996 Jun;122(6):627-32. doi: 10.1001/archotol.1996.01890180035010.
Recent basic discoveries about the biological significance of nuclear and cell-surface marker proteins have opened new areas of research into head and neck cancer. However, the clinical significance of these markers is not yet understood.
To perform a historical prospective study of 70 patients with squamous cell carcinoma of the larynx who were treated at our institution between 1979 and 1989 to correlate tumor marker expression with survival and metastasis.
Archival tissue was immunohistochemically stained for the p53 tumor suppressor gene product, the inhibitor of apoptosis (bcl-2), the stem cell marker CD34, the cell adhesion molecules CD44H and CD44v6, and a marker of cellular proliferation (Ki-67). The slides were examined using a light microscope and scored according to intensity and percentage of cells labeled. The patients were stratified by tumor stage, and survival and metastatic data were correlated with staining scores.
For the stage IV group, increased expression of p53 and decreased expression of CD44H and CD44v6 correlated with a decreased survival (P = .03, P = .03, and P = .02, respectively), and decreased expression of CD44H correlated with an increase in metastasis (P = .01). For all stages, excluding metastatic cases, increased p53 expression was consistent with a shorter survival (P < .03), while increased CD44v6 expression was consistent with a longer survival (P < .02).
The present study suggests that a loss of cell proliferation control implied by overexpression of p53 and loss of cell adhesion implied by decreased expression of CD44 may be determinants of survival in patients with carcinoma of the larynx. The tumor markers bcl-2 and Ki-67 were not prognostic discriminators in this limited series. This study also indicates that the stem cell marker CD34 is rarely expressed by laryngeal carcinoma cells.
近期关于核标记蛋白和细胞表面标记蛋白生物学意义的基础研究发现为头颈癌研究开辟了新领域。然而,这些标记物的临床意义尚不清楚。
对1979年至1989年在我院接受治疗的70例喉鳞状细胞癌患者进行一项历史性前瞻性研究,以关联肿瘤标记物表达与生存及转移情况。
对存档组织进行免疫组织化学染色,检测p53肿瘤抑制基因产物、凋亡抑制因子(bcl-2)、干细胞标记物CD34、细胞黏附分子CD44H和CD44v6以及细胞增殖标记物(Ki-67)。使用光学显微镜检查玻片,并根据标记细胞的强度和百分比进行评分。患者按肿瘤分期分层,生存和转移数据与染色评分相关联。
对于IV期组,p53表达增加以及CD44H和CD44v6表达降低与生存率降低相关(分别为P = 0.03、P = 0.03和P = 0.02),而CD44H表达降低与转移增加相关(P = 0.01)。对于所有分期,排除转移病例后,p53表达增加与生存期缩短一致(P < 0.03),而CD44v6表达增加与生存期延长一致(P < 0.02)。
本研究表明,p53过表达所暗示的细胞增殖控制丧失以及CD44表达降低所暗示的细胞黏附丧失可能是喉癌患者生存的决定因素。在这个有限的系列研究中,肿瘤标记物bcl-2和Ki-67不是预后判别指标。本研究还表明,干细胞标记物CD34在喉癌细胞中很少表达。