Wu C S, Pollack A, Czerniak B, Chyle V, Zagars G K, Dinney C P, Hu S X, Benedict W F
Department of Experimental Radiotherapy, University of Texas, M.D. Anderson Cancer Center, Houston, USA.
Urology. 1996 Mar;47(3):305-10. doi: 10.1016/s0090-4295(99)80443-9.
The relationship of p53 mutations as analyzed immunohistochemically to radiation response and therapeutic outcome was examined in a cohort of 301 patients with muscle-invasive transitional cell carcinoma of the bladder treated relatively uniformly with preoperative radiotherapy (50 Gy in 25 fractions) 4 to 6 weeks prior to radical cystectomy.
Adequate formalin-fixed paraffin-embedded archival tissue for the immunohistochemical staining of p53 using antibody DO1 was obtained in 109 patients. The median follow-up for those living was 91 months.
Overall, p53 staining was positive in 56% of the cases, with 60% positive in Stage T2 (n = 48), 42% in Stage T3a (n = 31), and 63% in Stage T3b (n = 30). Overexpression of p53 did not correlate with actuarial local control, distant metastasis freedom, disease freedom, or overall survival. However, significant associations were seen when these analyses were limited to patients with clinical Stage T3b disease. In this subgroup, the actuarial 5-year rates for patients with p53 positively and negatively stained tumors were 55% and 100%, respectively, for distant metastasis freedom (P = 0.01), 51% and 91% for disease freedom (P = 0.04), and 32% and 91% for overall survival (P = 0.006). Cox proportional hazards models that included p53 staining and other prognostic factors of significance in the univariate analyses revealed p53 to be independently predictive of survival for patients with Stage T3b disease.
The prognostic value of p53 immunostaining rested with Stage T3b patients. Although no correlations were found with radiation response, p53 positivity in this subgroup was associated with a higher rate of distant metastasis and reduced overall survival. For these patients, p53 negativity would indicate that aggressive local treatment (that is, preoperative radiotherapy and cystectomy) is sufficient, whereas p53 positivity would indicate that multiagent chemotherapy is required because of the increased risk of distant metastasis.
在一组301例肌肉浸润性膀胱移行细胞癌患者中，研究术前4至6周接受相对统一的术前放疗（25次分割，共50 Gy）后，通过免疫组织化学分析的p53突变与放射反应及治疗结果之间的关系。这些患者随后接受了根治性膀胱切除术。
109例患者获得了足够的福尔马林固定石蜡包埋存档组织，用于使用抗体DO1进行p53免疫组织化学染色。存活患者的中位随访时间为91个月。
总体而言，56%的病例p53染色呈阳性，T2期（n = 48）为60%，T3a期（n = 31）为42%，T3b期（n = 30）为63%。p53的过表达与精算局部控制、无远处转移、无疾病生存或总生存率均无相关性。然而，当这些分析仅限于临床T3b期疾病患者时，发现了显著的关联。在这个亚组中，p53染色阳性和阴性肿瘤患者的精算5年无远处转移率分别为55%和100%（P = 0.01），无疾病生存率分别为51%和91%（P = 0.04），总生存率分别为32%和91%（P = 0.006）。包含p53染色和单变量分析中有意义的其他预后因素的Cox比例风险模型显示，p53是T3b期疾病患者生存的独立预测因素。
p53免疫染色的预后价值取决于T3b期患者。虽然未发现与放射反应相关，但该亚组中p53阳性与更高的远处转移率和更低的总生存率相关。对于这些患者，p53阴性表明积极的局部治疗（即术前放疗和膀胱切除术）就足够了，而p53阳性则表明由于远处转移风险增加，需要多药化疗。
