HIF-1α表达与乳腺癌分级及分子亚型的关系研究

Relationship of HIF-1α expression with different grades and molecular subtypes of breast cancers

目的观察不同级别和不同分子亚型乳腺癌中HIF-1α的表达,探讨HIF-1α在乳腺癌中表达的意义。方法收集乳腺癌病例105例和正常对照17例,根据2012 WHO乳腺肿瘤中的标准进行分级,通过免疫组化检测各级中HIF-1α、ER、PR和HER-2的表达并根据常用的四分型法进行分型。结果 HIF-1α在正常乳腺和各级乳腺癌中的表达差异有统计学意义(P<0.05),其中Ⅱ级、Ⅲ级乳腺癌中的HIF-1α表达阳性率(76.19%和80.00%)高于正常乳腺和Ⅰ级乳腺癌(17.65%和23.53%)(P<0.01),正常乳腺(17.65%)、Ⅰ级(23.53%)之间以及Ⅱ级(76.19%)、Ⅲ级(80.00%)之间的表达无差异(P>0.05)。105例乳腺癌中各分子亚型HIF-1α表达的阳性率无差别,且均未检测到HIF-1α的表达与ER、PR和HER-2的相关性(P>0.05)。但不同级别乳腺癌中各分子亚型分布情况有差异(P<0.05)。结论 HIF-1α可能在恶性度较高的乳腺癌中起着更重要的调控作用,而HIF-1α与乳腺癌分子亚型的关系仍需进一步探讨,为HIF-1α为靶点的个体化治疗奠定基础。

Objective To determine the expression levels of hypoxia inducible factor-1α（HIF-1α）in breast cancers atdifferent histological grades and with different molecular subtypes in order to explore the significance of HIF-1α expression inthe cancer. Methods Breast cancer tissues from 105 patients with complete clinical data admitted in our hospital from 2011 to 2013 were collected,and another 17 normal breast samples served as normal control. WHO Classification of Tumors of theBreast,2012 was used to grade the obtained tumor samples. Immunohistochemical assay was employed to detect the expressionof HIF-1α,estrogen receptor（ER）,progesterone receptor（PR）,and HER2 to classify the cancer tissues into 4 conventionalmolecular subtypes. Results The positive expression ratio of HIF-1α had significant differences among normal breast tissue,and Grade Ⅰ to Ⅲ breast cancer（P〈0.05）. The positive ratio was higher in Grade Ⅱ and Grade Ⅲ（76.19% and 80.00%）than in normal breast tissue and Grade Ⅰ（17.65% and 23.53%,P〈0.01）,but no significant difference was seen betweennormal breast tissue and Grade Ⅰ（P〉0.05）,or between Grade Ⅱ and Grade Ⅲ（P〉0.05）. Moreover,there was no obviousdifference in the HIF-1α expression among 4 molecular subtypes of the 105 breast cancer cases,or correlation of HIF-1αexpression level with those of ER,PR and HER- 2（P〉0.05）. But the distributions of molecular subtypes was remarkablydifferent among different grades of breast cancer（P〈0.05）. Conclusion HIF- 1α may play a more significant role inmodulating the high grade breast cancer. But further research is needed on the relationship between HIF-1α and the subtypesin order to found a basis for the HIF-1α targeted therapy.