2nd Department of Gynecology, Lublin Medical University, Lublin, Poland.
Int J Gynecol Cancer. 2010 Aug;20(6):993-9. doi: 10.1111/IGC.0b013e3181e76a4d.
Alterations of p53 pathway (p14(ARF)/MDM2/p53) play a crucial role in the development and progression of various human neoplasms, including endometrial carcinoma (EC). The aim of the current research was to examine the p14(ARF) expression pattern in primary ECs and corresponding metastatic lesions.
We studied 47 primary ECs and corresponding metastatic lesions applying immunohistochemistry and investigated the relationship between p14(ARF) overexpression and clinicopathological variables of carcinoma as well as TP53 alterations.
Protein expression was predominantly nuclear, present in 32 (68%) of 47 primary cases and in 28 (60%) of 47 metastatic lesions. There were seven p14(ARF)-positive primary tumors showing negative reactivity in the metastatic lesions. On the other hand, 3 cases lacked protein immunoreactivity in the primary ECs but revealed weak nuclear staining in the corresponding metastases. A case of primary cervical adenocarcinoma metastasizing to the lymph nodes showed p14(ARF) expression both in the primary tumor and the corresponding metastases. A trend was found between the p14(ARF) expression in primary tumors and the presence of the neoplasms in the fallopian tube (P = 0.063), but none of the other clinicopathological variables of carcinoma was related to protein immunoreactivity in advanced-stage uterine neoplasms. The p14(ARF) expression in EC metastases was related to the presence of the primary tumor in the fallopian tube (P = 0.036). The p14(ARF) expression was not associated with unfavorable outcome both in the primary tumors (P = 0.302) and in the corresponding metastases (P = 0.217). There was also no relationship between the p14(ARF) expression pattern and TP53 pathway alterations.
Altogether, the p14(ARF) protein is expressed in more than half of the primary ECs and metastatic lesions analyzed and is associated with the transtubal dissemination of the primary tumor. The pattern of the p14(ARF) expression is not associated with the alterations of other TP53 pathway members in advanced-stage human ECs.
p53 通路（p14(ARF)/MDM2/p53）的改变在各种人类肿瘤的发生和发展中起着至关重要的作用，包括子宫内膜癌（EC）。本研究的目的是检测原发性 EC 及其相应转移病灶中 p14(ARF)的表达模式。
我们应用免疫组织化学方法研究了 47 例原发性 EC 及其相应的转移病灶，研究了 p14(ARF)过表达与癌的临床病理变量以及 TP53 改变之间的关系。
蛋白质表达主要为核内表达，在 47 例原发性病例中有 32 例（68%）和在 47 例转移性病变中有 28 例（60%）为阳性。有 7 例原发性肿瘤 p14(ARF)阳性，但在转移病灶中无反应性。另一方面，有 3 例原发性 EC 缺乏蛋白免疫反应性，但在相应的转移灶中显示弱阳性核染色。一例原发于宫颈的腺癌转移至淋巴结，在原发肿瘤和相应的转移灶中均显示 p14(ARF)表达。在原发性肿瘤中发现 p14(ARF)表达与输卵管内肿瘤的存在之间存在趋势（P=0.063），但晚期子宫肿瘤的其他临床病理变量均与蛋白免疫反应性无关。EC 转移灶中 p14(ARF)的表达与原发性肿瘤在输卵管中的存在有关（P=0.036）。p14(ARF)的表达与原发性肿瘤（P=0.302）和相应的转移灶（P=0.217）的不良预后均无关。p14(ARF)的表达模式与 TP53 通路改变之间也没有关系。
总之，在分析的原发性 EC 和转移性病变中，超过一半的原发性 EC 和转移性病变表达 p14(ARF)蛋白，并与原发性肿瘤的输卵管播散有关。在晚期人类 EC 中，p14(ARF)的表达模式与其他 TP53 通路成员的改变无关。
