Nardon E, Buda I, Stanta G, Buratti E, Fonda M, Cattin L
Department of Clinical, Morphological and Technological Sciences, University of Trieste, Italy.
J Clin Pathol. 2003 Aug;56(8):599-604. doi: 10.1136/jcp.56.8.599.
BACKGROUND/AIMS: A twofold increased risk for breast cancer has been reported recently for women with late onset diabetes. Most studies showed that there were differences in serum concentrations of insulin-like growth factors and related proteins between women with and without diabetes who have breast cancer. This study investigated the expression of these markers at the cellular level in a cohort of women with and without type 2 diabetes who underwent biopsy because of a breast lump.
Relative quantitative analysis of specific mRNA sequences was performed after extraction and reverse transcription polymerase chain reaction amplification from formalin fixed and paraffin wax embedded tissues. Sixty seven breast surgical specimens from women with and without diabetes who did not have cancer and from women with and without diabetes who did have cancer were studied for insulin-like growth factor I (IGF-I), the IGF-I receptor (IGF-IR), insulin-like growth factor binding protein 3 (IGFBP-3), and oestrogen receptor 1 gene expression.
The expression of IGF-I and IGF-IR was significantly lower in the cancer groups, whereas there was no significant difference for IGFBP-3 between women with and without cancer. Moreover, there was a good correlation between the expression of IGF-I and IGF-IR in women without cancer: this link was still present in breast tissue from patients with diabetes and cancer, whereas it was lost in patients without diabetes but with cancer.
These differences in IGF-I/IGF-IR expression could contribute to the increased risk for breast cancer in women with type 2 diabetes.
背景/目的:最近有报道称,晚发型糖尿病女性患乳腺癌的风险增加了两倍。大多数研究表明,患有乳腺癌的糖尿病女性和非糖尿病女性血清中胰岛素样生长因子及相关蛋白的浓度存在差异。本研究在一组因乳腺肿块接受活检的2型糖尿病女性和非糖尿病女性中,从细胞水平研究了这些标志物的表达情况。
从福尔马林固定、石蜡包埋组织中提取RNA并进行逆转录聚合酶链反应扩增后,对特定mRNA序列进行相对定量分析。对67例来自患癌和未患癌的糖尿病女性及非糖尿病女性的乳腺手术标本,研究胰岛素样生长因子I(IGF-I)、IGF-I受体(IGF-IR)、胰岛素样生长因子结合蛋白3(IGFBP-3)和雌激素受体1基因的表达。
IGF-I和IGF-IR的表达在癌症组中显著降低,而患癌和未患癌女性的IGFBP-3表达无显著差异。此外,未患癌女性中IGF-I和IGF-IR的表达之间存在良好的相关性:在糖尿病合并癌症患者的乳腺组织中这种联系仍然存在,而在非糖尿病但患癌患者中则消失了。
IGF-I/IGF-IR表达的这些差异可能导致2型糖尿病女性患乳腺癌的风险增加。