Ozretic Petar, Alvir Ilija, Sarcevic Bozena, Vujaskovic Zeljko, Rendic-Miocevic Zrinka, Roguljic Ana, Beketic-Oreskovic Lidija
1 Laboratory for Hereditary Cancer, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb - Croatia.
2 Department of Gynecologic Oncology, University Hospital for Tumors, Sestre Milosrdnice Clinical Hospital Center, Zagreb - Croatia.
Int J Biol Markers. 2018 Jan;33(1):109-115. doi: 10.5301/ijbm.5000291.
The objective of this study was to examine the prognostic significance of carbonic anhydrase IX (CAIX), an endogenous marker for tumor hypoxia; the cellular tumor antigen p53; and the apoptosis regulator Bcl-2, in triple-negative breast cancer (TNBC) patients.
Immunohistochemically determined expression of CAIX, p53, Bcl-2 and proliferation factor Ki-67, analyzed in 64 paraffin-embedded TNBC tissue samples, was used to assess their relation to clinicopathological variables and prognostic implications for overall survival (OS).
Bcl-2 expression was negatively correlated with histological grade of tumor, while expression of p53 was positively correlated with the same clinical variable (p = 0.036 and p = 0.033, respectively). The p53 expression was also positively correlated with tumor size (p = 0.010). Survival analysis showed that patients with high Bcl-2 expression (above cutoff value determined by receiver operator characteristic [ROC] curve analysis) had shorter OS (p = 0.020). The same was observed for patients with tumors larger than 5 cm (p = 0.034) or positive lymph nodes (p = 0.004). Among all 3 examined markers, multivariate analysis showed that only Bcl-2 expression was a strong independent prognostic indicator for decreased OS (hazard ratio [HR] = 15.16, 95% confidence interval [95% CI], 2.881-79.727, p = 0.001).
Elevated expression of Bcl-2 was an independent prognostic factor for poorer OS in TNBC and as such a significant marker for tumor aggressiveness.
本研究的目的是检测碳酸酐酶IX（CAIX，一种肿瘤缺氧的内源性标志物）、细胞肿瘤抗原p53和凋亡调节因子Bcl-2在三阴性乳腺癌（TNBC）患者中的预后意义。
通过免疫组织化学方法测定64例石蜡包埋的TNBC组织样本中CAIX、p53、Bcl-2和增殖因子Ki-67的表达，以评估它们与临床病理变量的关系以及对总生存期（OS）的预后影响。
Bcl-2表达与肿瘤组织学分级呈负相关，而p53表达与相同临床变量呈正相关（分别为p = 0.036和p = 0.033）。p53表达也与肿瘤大小呈正相关（p = 0.010）。生存分析显示，Bcl-2高表达（高于通过受试者工作特征[ROC]曲线分析确定的临界值）的患者OS较短（p = 0.020）。肿瘤大于5 cm（p = 0.034）或有阳性淋巴结的患者也观察到同样情况（p = 0.004）。在所有检测的3个标志物中，多变量分析显示只有Bcl-2表达是OS降低的一个强有力的独立预后指标（风险比[HR]=15.16，95%置信区间[95%CI]，2.881 - 79.727，p = 0.001）。
Bcl-2表达升高是TNBC患者OS较差的独立预后因素，因此是肿瘤侵袭性的一个重要标志物。
