Lewis D J, Sesterhenn I A, McCarthy W F, Moul J W
Department of Surgery and Clinical Investigation, Walter Reed Army Medical Center, Washington, D. C.
J Urol. 1994 Aug;152(2 Pt 1):418-23. doi: 10.1016/s0022-5347(17)32753-2.
P53 tumor suppressor gene protein immunostaining was evaluated in the primary tumor of adult testicular germ cell cancer to assess if P53 expression would serve as a clinically useful tumor marker. Representative archival tissues from 152 orchiectomy specimens were studied for P53 immunohistochemistry. Seminoma and nonseminomatous germ cell tumor constituents revealed P53 expression via immunohistochemistry in 90% and 94% of the cases, respectively. For seminoma, there was a trend toward decreased P53 expression with advancing stage. For nonseminomatous germ cell tumor, although all cellular components showed variable P53 expression, P53 expression in embryonal carcinoma constituents increased among stages of disease. A third of pathological stage I cancer patients exhibited 2+ or greater P53-embryonal staining compared with 61% with stage II (p = 0.0670) and 67% with stage III (p = 0.0815) disease, respectively (Kruskal-Wallis, 2-sided test). As a secondary objective, we wanted to determine if P53 immunohistochemistry would be useful to predict occult disease in clinical stage I nonseminomatous germ cell tumor. This group was studied for P53-embryonal immunohistochemistry, the presence of vascular invasion and the quantitative determination of percentage of embryonal carcinoma in the primary tumor in a multivariate fashion to assess if these tests could be clinically useful to predict occult disease. Degree of P53 immunostaining of the embryonal component in the primary tumor was statistically greater for stage II by univariate logistic regression analysis (p = 0.0362). Similarly, the per cent embryonal cancer (p = 0.0002) and vascular invasion (p = 0.0005) were highly significant as predictors of occult stage II disease via the univariate testing. By multivariate logistic regression analysis, the model consisting of per cent embryonal cancer and vascular invasion provided the best prediction of occult disease in the clinical stage I cohort. In addition, this model had the highest sensitivity and specificity of all multivariate models considered. The addition of P53-embryonal staining did not improve predictability nor sensitivity/specificity. The P53 tumor suppressor gene protein is expressed to some degree in most testicular germ cell tumors and degree of staining/expression varies according to stage of disease. From the standpoint of a clinically useful primary tumor risk factor for predicting occult disease, vascular invasion by the tumor and percentage of embryonal carcinoma component in the tumor are more useful than P53 immunohistochemistry.
在成年睾丸生殖细胞癌的原发性肿瘤中评估了P53肿瘤抑制基因蛋白免疫染色，以评估P53表达是否可作为一种临床有用的肿瘤标志物。对152例睾丸切除术标本的代表性存档组织进行了P53免疫组织化学研究。精原细胞瘤和非精原细胞性生殖细胞肿瘤成分通过免疫组织化学分别在90%和94%的病例中显示出P53表达。对于精原细胞瘤，随着分期进展，P53表达有降低趋势。对于非精原细胞性生殖细胞肿瘤，尽管所有细胞成分均显示出可变的P53表达，但胚胎癌成分中的P53表达在疾病各阶段中增加。三分之一的病理I期癌症患者表现出2+或更强的P53-胚胎染色，而II期患者为61%（p = 0.0670），III期患者为67%（p = 0.0815）（Kruskal-Wallis双侧检验）。作为次要目标，我们想确定P53免疫组织化学是否有助于预测临床I期非精原细胞性生殖细胞肿瘤中的隐匿性疾病。对该组进行了P53-胚胎免疫组织化学、血管侵犯情况以及原发性肿瘤中胚胎癌百分比的定量测定，采用多变量方式评估这些检测是否在临床上有助于预测隐匿性疾病。通过单变量逻辑回归分析，原发性肿瘤中胚胎成分的P53免疫染色程度在II期时在统计学上更高（p = 0.0362）。同样，通过单变量检测，胚胎癌百分比（p = 0.0002）和血管侵犯（p = 0.0005）作为隐匿性II期疾病的预测指标具有高度显著性。通过多变量逻辑回归分析，由胚胎癌百分比和血管侵犯组成的模型对临床I期队列中的隐匿性疾病提供了最佳预测。此外，该模型在所有考虑的多变量模型中具有最高的敏感性和特异性。添加P53-胚胎染色并未提高预测性或敏感性/特异性。P53肿瘤抑制基因蛋白在大多数睾丸生殖细胞肿瘤中均有一定程度表达，且染色/表达程度因疾病分期而异。从作为预测隐匿性疾病的临床有用的原发性肿瘤危险因素的角度来看，肿瘤的血管侵犯和肿瘤中胚胎癌成分的百分比比P53免疫组织化学更有用。
