Hypoxic status in ovarian serous and mucinous tumors:: relationship between histological characteristics and HIF-1α/GLUT-1 expression

Hypoxic status in ovarian serous and mucinous tumors:: relationship between histological characteristics and HIF-1α/GLUT-1 expression
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DOI:
10.1007/s00404-007-0500-8
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发表时间:
2008-06-01
影响因子:
2.6
通讯作者:
Mikami, Mikio
Mikami, Mikio
中科院分区:
医学3区
文献类型:
--
作者:
Iida, Tetsuji;Yasuda, Masanori;Mikami, Mikio

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材料与方法应用免疫组织化学方法,从卵巢浆液性和粘液性肿瘤的组织学特点和恶性获得的角度,分析低氧诱导因子-1α(HIF-1α)和葡萄糖转运蛋白-1(GLUT-1)在卵巢浆液性和粘液性肿瘤中的表达。共检查卵巢肿瘤102例,其中腺瘤31例(浆液性17例,粘液性14例),交界性肿瘤32例(浆液性13例,粘液性19例),腺癌39例(浆液性21例,粘液性18例)。结果HIF-1α、腺瘤74%、交界性肿瘤91%、腺癌100%;腺瘤、交界性肿瘤和腺癌的HIF-1α和GLUT-1阳性率与浆液性肿瘤和粘液性肿瘤相比差异无统计学意义。然而,两种标记物在浆液性腺癌中的表达(HIF-1α,3+100%;GLUT-1,3+76%)均高于粘液性腺癌(HIF-1α,3+61%;GLUT-1,3+28%)。免疫印迹和mRNA表达水平分析结果与免疫组织化学表达谱结果一致。DNA结合分析还表明,HIF-1在浆液性腺癌中比在粘液性腺癌中更常见地被激活。结论HIF-1α和GLUT-1的表达协同作用,使卵巢肿瘤细胞适应低氧环境,与肿瘤的发生密切相关。我们认为这两种标记物在浆液性肿瘤中的表达相对粘液性肿瘤相对较强,这与它们的组织学特征不同有关。
Material and methods We analyzed the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha) and glucose transporter-1 (GLUT-1) by immunohistochemistry in ovarian serous and mucinous tumors from the point view of the histological characteristics and acquisition of malignancy. A total of 102 ovarian tumors were examined, composed of 31 adenomas (serous 17 and mucinous 14), 32 borderline tumors (serous 13 and mucinous 19), and 39 adenocarcinomas (serous 21 and mucinous 18).Results The overall positive ratios were as follows: HIF-1 alpha, 74% of adenomas, 91% of borderline tumors, and 100% of adenocarcinomas; and GLUT-1, 68% of adenomas, 95% of borderline tumors, and 100% of adenocarcinomas. Comparing serous tumors and mucinous tumors, there was no significant difference in the positive ratios of HIF-1 alpha and GLUT-1 of adenomas, borderline tumors, and adenocarcinomas. However, both markers were more strongly expressed in serous adenocarcinomas (HIF-1 alpha, 3 + 100%; GLUT-1, 3 + 76%) than in mucinous adenocarcinomas (HIF-1 alpha, 3 + 61%; GLUT-1, 3 + 28%). The results of immunoblotting and mRNA expression level analyses corresponded with those of immunohistochemical expression profiles. DNA binding assay also demonstrated that HIF-1 is more commonly activated in serous adenocarcinomas than in mucinous adenocarcinomas.Conclusion HIF-1 alpha and GLUT-1 expressions seemed to be coordinated to adapt ovarian tumor cells into hypoxic conditions in close association with the acquisition of malignancy. We consider that the relatively strong expression of both markers in serous tumors compared with mucinous tumors is related to the difference in their histological characteristics.