Huvila Jutta, Brandt Annika, Rojas Clarissa Rios, Pasanen Salla, Talve Lauri, Hirsimäki Pirkko, Fey Vidal, Kytömäki Leena, Saukko Pekka, Carpén Olli, Soini Juhani T, Grénman Seija, Auranen Annika
Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland.
Int J Gynecol Cancer. 2009 Oct;19(7):1226-31. doi: 10.1111/IGC.0b013e3181b33be0.
Tumor grade is one of the most important prognostic factors in endometrioid endometrial adenocarcinoma. Amplification of oncogenes, such as Her2/neu, or loss of function of tumor suppressor genes, such as p53, are known to be associated with poor prognosis, but additional factors influencing clinical behavior are likely to exist. To examine the biological differences between low-grade and high-grade endometrioid endometrial adenocarcinomas, we compared gene expression in these 2 types of tumors.
Six well-differentiated adenocarcinomas and 7 poorly differentiated adenocarcinomas were studied with 2 different microarray platforms, Affymetrix and Illumina. The expression of the most differentially expressed gene on both platforms was further studied in 34 endometrial adenocarcinoma samples (10 well differentiated, 9 moderately differentiated, and 15 poorly differentiated) using real-time reverse transcription-polymerase chain reaction.
The most differentially expressed gene on both platforms was Apolipoprotein E (APOE). In the poorly differentiated adenocarcinomas, APOE was overexpressed 13.1-fold (P = 0.001) and 9.7-fold (P = 0.007) when compared with well- and moderately differentiated tumors, respectively. There was no difference in APOE expression between well- and moderately differentiated adenocarcinomas.
Increased expression of APOE might represent a late event in the progression of well-differentiated endometrioid endometrial adenocarcinoma to a poorly differentiated endometrioid endometrial adenocarcinoma. Although increased APOE expression has been previously reported in other malignancies, this is the first study to suggest that APOE might also have a role in endometrioid endometrial cancer.
肿瘤分级是子宫内膜样腺癌最重要的预后因素之一。已知癌基因（如Her2/neu）的扩增或肿瘤抑制基因（如p53）的功能丧失与预后不良相关，但可能还存在影响临床行为的其他因素。为了研究低级别和高级别子宫内膜样腺癌之间的生物学差异，我们比较了这两种肿瘤的基因表达情况。
使用Affymetrix和Illumina这两种不同的微阵列平台，对6例高分化腺癌和7例低分化腺癌进行了研究。使用实时逆转录-聚合酶链反应，在34例子宫内膜腺癌样本（10例高分化、9例中分化和15例低分化）中进一步研究了两个平台上差异表达最明显的基因的表达情况。
两个平台上差异表达最明显的基因都是载脂蛋白E（APOE）。与高分化和中分化肿瘤相比，在低分化腺癌中，APOE的表达分别上调了13.1倍（P = 0.001）和9.7倍（P = 0.007）。高分化和中分化腺癌之间的APOE表达没有差异。
APOE表达增加可能代表高分化子宫内膜样腺癌进展为低分化子宫内膜样腺癌过程中的一个晚期事件。虽然之前在其他恶性肿瘤中也曾报道过APOE表达增加，但本研究首次表明APOE可能在子宫内膜样腺癌中也发挥作用。
