Zheng W, Sung C J, Cao P, Zhang Z F, Cai R, Godwin T A, Kramer E E, Lauchlan S C
Department of Pathology, University of Southern California School of Medicine, Los Angeles, USA.
Gynecol Oncol. 1997 Jan;64(1):38-48. doi: 10.1006/gyno.1996.4519.
The pathogenesis of primary carcinoma of the fallopian tube (PCFT) is poorly understood. Tumor suppressor p53 gene alterations are common in human malignancies, but their role in the tumorigenesis and survival of PCFT is undefined. The objectives of this study were to define the occurrence and prognostic role of p53 alteration in PCFT and to examine the efficiency of immunohistochemistry (IHC) in detecting p53 alteration in PCFT. Fifty-two PCFT and 10 normal fallopian tubes were examined for p53 alteration by IHC and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). The Kaplan-Meier method was used to derive the survival function, while the log-rank test was used to compare curves for two or more groups. Other patients' characteristics were analyzed by two-tailed Fisher's exact tests. IHC correlated well with PCR-SSCP with 100% sensitivity and 83.3% specificity for detecting p53 alteration in this study. Thirty-one of 52 (57%) PCFT showed p53 alteration. Alteration of p53 occurred in all stages of PCFT with a similar incidence in carcinoma in situ and late-stage disease. Alteration of p53 was related to tumor histologic type. Significant survival difference was noted between advanced and early clinical stages but no such difference was identified among different tumor grades. Compared to the p53-nonaltered group, the presence of p53 alteration in PCFT was related to significantly decreased patient survival (RR = 6.8, 95% CI = 2.9-16.2) in multivariate analysis. In the subgroup of patients with residual tumor after surgery, those with p53-altered tumors had a significantly decreased survival compared to those with p53-nonaltered group (RR = 7.4, 95% CI = 1.9-28.2). Alteration of p53 is common and IHC is an efficient method to detect p53 alteration in PCFT. Shorter survival is associated with p53 alteration which is an independent marker for the disease in this study. Alteration of p53 may be an early event in tubal tumorigenesis and may play an important role in the development of PCFT. Whether detection of p53 alteration may serve as an indicator of high-risk patients for whom more aggressive adjuvant chemotherapy may be considered needs to be explored in the future.
原发性输卵管癌（PCFT）的发病机制尚不清楚。肿瘤抑制基因p53的改变在人类恶性肿瘤中很常见，但其在PCFT的肿瘤发生和生存中的作用尚不清楚。本研究的目的是确定p53改变在PCFT中的发生率和预后作用，并检验免疫组织化学（IHC）检测PCFT中p53改变的效率。通过IHC和聚合酶链反应-单链构象多态性（PCR-SSCP）检测了52例PCFT和10例正常输卵管的p53改变。采用Kaplan-Meier法推导生存函数，采用对数秩检验比较两组或多组曲线。其他患者特征采用双侧Fisher精确检验进行分析。在本研究中，IHC与PCR-SSCP检测p53改变的相关性良好，敏感性为100%，特异性为83.3%。52例PCFT中有31例（57%）显示p53改变。p53改变发生在PCFT的各个阶段，原位癌和晚期疾病的发生率相似。p53改变与肿瘤组织学类型有关。晚期和早期临床阶段之间存在显著的生存差异，但不同肿瘤分级之间未发现此类差异。在多变量分析中，与p53未改变组相比，PCFT中p53改变的存在与患者生存率显著降低相关（RR = 6.8，95% CI = 2.9-16.2）。在术后有残留肿瘤的患者亚组中，p53改变的肿瘤患者与p53未改变组相比，生存率显著降低（RR = 7.4，95% CI = 1.9-28.2）。p53改变很常见，IHC是检测PCFT中p53改变的有效方法。较短的生存期与p53改变相关，p53改变是本研究中该疾病的一个独立标志物。p53改变可能是输卵管肿瘤发生的早期事件，可能在PCFT的发展中起重要作用。p53改变的检测是否可作为高危患者的指标，对于这些患者是否可考虑更积极的辅助化疗，未来有待探索。
