Sauter E R, Cleveland D, Trock B, Ridge J A, Klein-Szanto A J
Department of Surgery, Fox Chase Cancer Center, Philadelphia, PA 19111.
Carcinogenesis. 1994 Oct;15(10):2269-74. doi: 10.1093/carcin/15.10.2269.
To identify the stage in head and neck carcinogenesis at which p53 abnormalities become important, we evaluated 512 squamous epithelial tissue samples (201 pre-invasive and 209 invasive lesions, as well as 102 normal epithelia) in specimens from two institutions. Of 311 patients evaluated, 128 did not have an invasive carcinoma. The frequency of p53 overexpression in the pre-invasive lesions was not influenced by an adjacent invasive tumor. There was an increasing frequency of p53 overexpression in specimens from histologically normal epithelium (5%, with only scattered basal layers positive) to mild (28%) and moderate dysplasia (47%). p53 overexpression was also significantly more common in lesions with severe dysplasia (54%) and carcinoma in situ (CIS; 50%) than in those with mild dysplasia. To further evaluate the timing of p53 alterations in the development of head and neck cancer, paired epithelial samples (one pre-invasive and one invasive) from the same patient were evaluated. A discordance in the p53 staining pattern was seen in approximately one-third of the cases. When a discordance was present, the frequency with which the invasive lesion was positive but the non-invasive negative decreased from 97% (invasive versus normal epithelium) to 50% (invasive versus severe dysplasia or CIS). When p53 expression was evaluated by site, buccal lesions appeared to overexpress p53 more frequently than tongue lesions. In conclusion, p53 protein overexpression is an early event in head and neck carcinogenesis and may represent a biomarker for patients with pre-invasive lesions.
为了确定p53异常在头颈部癌发生过程中变得重要的阶段，我们评估了来自两个机构标本中的512个鳞状上皮组织样本（201个癌前病变和209个浸润性病变，以及102个正常上皮）。在评估的311例患者中，128例没有浸润性癌。癌前病变中p53过表达的频率不受相邻浸润性肿瘤的影响。从组织学正常上皮（5%，仅散在的基底层阳性）到轻度发育异常（28%）和中度发育异常（47%）的标本中，p53过表达的频率逐渐增加。p53过表达在重度发育异常（54%）和原位癌（CIS；50%）的病变中也比轻度发育异常的病变中显著更常见。为了进一步评估头颈部癌发生过程中p53改变的时间，对来自同一患者的配对上皮样本（一个癌前病变和一个浸润性病变）进行了评估。在大约三分之一的病例中观察到p53染色模式不一致。当出现不一致时，浸润性病变为阳性而非浸润性病变为阴性的频率从97%（浸润性病变与正常上皮相比）降至50%（浸润性病变与重度发育异常或CIS相比）。当按部位评估p53表达时，颊部病变似乎比舌部病变更频繁地过表达p53。总之，p53蛋白过表达是头颈部癌发生的早期事件，可能代表癌前病变患者的一种生物标志物。
