p53蛋白表达在肛管表皮样癌中的预后作用。

Prognostic role of p53 protein expression in epidermoid carcinoma of the anal canal.

作者信息

Wong C S, Tsao M S, Sharma V, Chapman W B, Pintilie M, Cummings B J

机构信息

Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Ontario, Canada.

出版信息

Int J Radiat Oncol Biol Phys. 1999 Sep 1;45(2):309-14. doi: 10.1016/s0360-3016(99)00188-1.

DOI:10.1016/s0360-3016(99)00188-1

PMID:10487550

Abstract

PURPOSE

To assess the prognostic significance of p53 protein expression in patients with primary epidermoid carcinoma of the anal canal managed by radiation therapy (XRT), 5-fluorouracil (5-FU), and mitomycin C (MMC).

METHODS AND MATERIALS

From January 1991 to December 1993, 58 consecutive patients with primary epidermoid carcinoma of the anal canal were treated in a prospectively designed protocol of XRT (24 Gy/12--3(1/2) wk split--28 Gy/14) and concurrent 5-FU (1000 mg/m2/day 1-4) and MMC (10 mg/m2 day 1) of each cycle of XRT. Paraffin-embedded tumor samples were unavailable in 9 patients, leaving 49 patients in the study. Expression of p53 protein was studied using immunohistochemistry and quantified as percent tumor nuclei showing positive staining. Actuarial survival and disease-free survival (DFS) rates were estimated by the Kaplan-Meier method, and compared using the log-rank test. A Cox proportional hazard model was used for the multivariable analysis.

RESULTS

There were 6 T1, 26 T2, 7 T3, and 10 T4 lesions. Primary tumor sizes ranged from 1-15 cm with a median of 4 cm. There were 6 patients with nodal metastases. Median follow-up was 4.5 years. Positive nuclear immunostaining for p53 was observed in 40 of 49 patients. The median percent positive staining was 5%, with 13, 9, and 18 patients showing staining in <5%, 5 to <10%, and 10-50% of tumor nuclei respectively. There was no correlation of percent p53 staining with gender, age, tumor stage, size, or histology. Local, regional, and distant failures were observed in 12, 2, and 2 patients respectively. The 5-yr survival and DFS were 84% and 64% respectively. In univariate analysis, the only prognostic variable for survival was gender. For DFS, advanced T category and large tumor size were predictive of poor DFS. In multivariate analysis, poor DFS was associated with high T category (p = 0.0008), basaloid histology (p = 0.001), male gender (p = 0.002), and increasing percent of p53 protein expression (p = 0.01).

CONCLUSIONS

It is concluded that expression for p53 protein is present in a high percentage of patients with epidermoid carcinoma of the anal canal. For patients managed with combined XRT, 5-FU, and MMC, percent p53 protein expression is of prognostic value for DFS independent of other clinical factors such as T category, gender, and histology.

摘要

目的

评估p53蛋白表达在接受放射治疗（XRT）、5-氟尿嘧啶（5-FU）和丝裂霉素C（MMC）治疗的原发性肛管表皮样癌患者中的预后意义。

方法和材料

1991年1月至1993年12月，58例连续的原发性肛管表皮样癌患者按照前瞻性设计的方案接受XRT（24 Gy/12 - 3(1/2)周分割 - 28 Gy/14）以及每个XRT周期同时使用5-FU（1000 mg/m²/天，第1 - 4天）和MMC（10 mg/m²，第1天）治疗。9例患者没有石蜡包埋的肿瘤样本，研究中剩余49例患者。使用免疫组织化学研究p53蛋白的表达，并将其量化为显示阳性染色的肿瘤细胞核百分比。采用Kaplan-Meier方法估计精算生存率和无病生存率（DFS），并使用对数秩检验进行比较。使用Cox比例风险模型进行多变量分析。

结果

有6个T1、26个T2、7个T3和10个T4病变。原发肿瘤大小范围为1 - 15 cm，中位数为4 cm。有6例患者有淋巴结转移。中位随访时间为4.5年。49例患者中有40例观察到p53核免疫染色阳性。阳性染色的中位数百分比为5%，分别有13、9和18例患者的肿瘤细胞核染色<5%、5%至<10%和10% - 50%。p53染色百分比与性别、年龄、肿瘤分期、大小或组织学无关。分别在12、2和2例患者中观察到局部、区域和远处复发。5年生存率和DFS分别为84%和64%。在单变量分析中，生存的唯一预后变量是性别。对于DFS，高T类别和大肿瘤大小预示着DFS较差。在多变量分析中，较差的DFS与高T类别（p = 0.0008）、基底样组织学（p = 0.001）、男性性别（p = 0.002）以及p53蛋白表达百分比增加（p = 0.01）相关。