Evidence for a latent precursor (p53 signature) that may precede serous endometrial intraepithelial carcinoma.
Evidence for a latent precursor (p53 signature) that may precede serous endometrial intraepithelial carcinoma.
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DOI：
10.1038/modpathol.2008.197
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Crum CP
中科院分区：
文献类型：
--
作者：
Jarboe EA;Pizer ES;Miron A;Monte N;Mutter GL;Crum CP
浆液性上皮内癌和子宫内膜腺体发育不良均与子宫浆液性癌有关。最近，在输卵管中描述了含有p53突变（p53签名）的候选浆液性癌前体。我们分析了正常和肿瘤性子宫内膜的相似实体。本文对10例上皮内癌和/或浸润性癌累及的子宫内膜息肉和137例良性息肉进行了研究。所有细胞均进行p53和MIB-1染色。分析了p53标签和癌的一个子集的γ-H2 AX和p53突变。10例上皮内癌中7例p53阳性，2例p53阳性为多中心性。在一个病例中，签名与上皮内癌连续。137例良性息肉中有6例（4%）含有p53标记。MIB-1在大多数信号中的分数小于5%，在癌中的范围为50-90%。DNA损伤（γ-H2 AX）在p53和癌旁组织中均有表达，但在良性息肉中无表达。共享相同的p53突变被发现在配对的签名和癌中的三个分析的情况下，包括一个案件与多个签名。在一个，共存的浸润性浆液性癌没有发现含有p53突变。在第三种情况下，p53签名和浸润性癌症具有两种不同的p53突变。这是第一个描述的p53签名附近的癌，这一实体的浆液性恶性肿瘤的发生中的作用。p53信号在良性病变（息肉）中的意义仍有待确定。
Both serous intraepithelial carcinoma and endometrial glandular dysplasia are associated with uterine serous carcinoma. Recently a candidate serous cancer precursor containing p53 mutations (p53 signature) was described in the fallopian tube. We analyzed normal and neoplastic endometrium for a similar entity. Ten endometrial polyps involved by intraepithelial and/or invasive carcinoma and 137 benign polyps were studied. All were stained for p53 and MIB-1. A subset of p53 signatures and carcinomas were analyzed for γ-H2AX and p53 mutations. p53 signatures were identified in 7 of 10 cases intraepithelial carcinoma and were multicentric in 2. In one case, the signature was in continuity with intraepithelial carcinoma. Six of 137 benign polyps (4%) contained p53 signatures. The MIB-1 fraction in most signatures was less than 5%, and ranged from 50-90% in carcinomas. DNA damage (γ-H2AX) was demonstrated in both p53 signatures and adjacent carcinomas but not in benign polyps. Shared identical p53 mutations were found in paired signatures and carcinomas in two of three cases analyzed, including one case with multiple signatures. In one, a co-existent invasive serous cancer was not found to contain a p53 mutation. In a third, a p53 signature and an invasive cancer harbored two different p53 mutations. This is the first description of p53 signatures adjacent to carcinoma, suggesting a role for this entity in the genesis of serous malignancy. The significance of p53 signatures in benign conditions (polyps) remains to be determined.
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