Ranade K J, Nerurkar A V, Phulpagar M D, Shirsat N V
Department of Biochemistry, T. N. Medical College, B. Y. L. Nair Hospital, Mumbai, India.
Indian J Med Sci. 2009 Nov;63(11):481-90.
In invasive ductal carcinoma (IDC), many antiapoptotic and proapoptotic genes regulate disease outcome. Hormone receptor-mediated mechanisms have also been shown to prevent apoptosis. Therefore, relations between hormone receptor status and other molecular markers need further examination.
In the present study, we analyzed the expression of apoptosis-regulating genes, viz., Survivin and mutant p53, in benign breast disease (fibroadenoma) and IDC patients. Results were then correlated with hormone receptor status of the patients.
Paraffin-embedded tissue samples from 63 untreated female patients with IDC and 32 female patients with fibroadenoma were used. Expression of Survivin and mutant p53 was evaluated using immunohistochemical staining method.
Fisher exact test and nonparametric correlation test (Spearman rank correlation test) were performed. Results : In fibroadenoma, 53% of patients expressed Survivin and 13% of patients expressed p53 protein. Statistically significant increase in Survivin and p53 protein expression was observed in carcinoma cases. Survivin expression correlated negatively with progesterone receptor (PR) status, but its expression was independent of estrogen receptor (ER) status. p53 expression showed negative correlation with both ER and PR status.
Increased expression of Survivin and p53 in IDC patients and correlation with hormone receptors suggest that Survivin and p53 along with hormone receptors status are likely to contribute significantly to apoptosis resistance and may serve as therapeutic target that could increase the effectiveness of conventional breast cancer therapy.
在浸润性导管癌(IDC)中,许多抗凋亡和促凋亡基因调节疾病预后。激素受体介导的机制也已被证明可预防细胞凋亡。因此,激素受体状态与其他分子标志物之间的关系需要进一步研究。
在本研究中,我们分析了凋亡调节基因Survivin和突变型p53在良性乳腺疾病(纤维腺瘤)和IDC患者中的表达。然后将结果与患者的激素受体状态相关联。
使用来自63例未经治疗的IDC女性患者和32例纤维腺瘤女性患者的石蜡包埋组织样本。采用免疫组织化学染色法评估Survivin和突变型p53的表达。
进行Fisher精确检验和非参数相关性检验(Spearman秩相关检验)。结果:在纤维腺瘤中,53%的患者表达Survivin,13%的患者表达p53蛋白。在癌病例中观察到Survivin和p53蛋白表达有统计学意义的增加。Survivin表达与孕激素受体(PR)状态呈负相关,但其表达与雌激素受体(ER)状态无关。p53表达与ER和PR状态均呈负相关。
IDC患者中Survivin和p53表达增加以及与激素受体的相关性表明,Survivin和p53连同激素受体状态可能对凋亡抵抗有显著贡献,并可能作为治疗靶点,从而提高传统乳腺癌治疗的有效性。