Mühlbeier Diego F M, Saddi Vera A, de Paula Élbio C, Cunha Isabela W, Fregnani José H T G, Barbosa Maria A, Manoel Wilmar J
*Master's Program in Genetics, Pontifical Catholic University of Goias †Pathology Department, Araújo Jorge Hospital, Association Against Cancer in Goias ∥Medical School, Graduate Program in Health Sciences, Federal University of Goias, Goiânia ‡Department of Pathological Anatomy, A.C. Camargo Cancer Hospital, São Paulo §Hospital of Cancer of Barretos, FundationPio XVII, Barretos, Brazil.
Appl Immunohistochem Mol Morphol. 2016 Apr;24(4):268-74. doi: 10.1097/PAI.0000000000000185.
Bcl-2 and Bax proteins are key regulators of apoptosis, a process that is deregulated in many human diseases, particularly cancer. Overexpression of antiapoptotic Bcl-2 protein is associated with drug resistance and poor clinical outcome in cancer patients, whereas the expression of proapoptotic Bax protein, commonly detected in soft-tissue sarcoma (STS), is often associated with chemiosensitivity in different tumors. Studies on the clinical implications of apoptosis-related markers Bcl-2 and Bax in STS are limited. In this study, immunohistochemistry for Bcl-2 and Bax was performed on tissue microarrays of 86 multiple types of adult STS of the extremities. Bcl-2 and Bax positive expression was detected in 25.9% and 66.7% of the sarcomas, respectively. Overexpression of both, Bcl-2 and Bax, was directly associated with histologic grade and clinical stage. A significant association between Bax and Bcl-2 expression was also observed (P=0.007). The 5-year overall survival for the group was 57%, and it was lower for cases that overexpressed Bcl-2 (47.6% vs. 58.3%) and Bax (50% vs. 66.7%), although not statistically significant. After multivariate analysis, only the high histologic grade appeared as an independent prognostic factor for the patients (P=0.043; HR=8.0; 95% CI, 1.1-60.1). In our study, Bcl-2 and Bax expression was significantly associated with histologic grade and clinical stage, which are classic factors of poor prognosis. We suggest the use of these proteins as potential prognostic markers in STS of extremities.
Bcl-2和Bax蛋白是细胞凋亡的关键调节因子，细胞凋亡这一过程在许多人类疾病尤其是癌症中失调。抗凋亡Bcl-2蛋白的过表达与癌症患者的耐药性及不良临床预后相关，而促凋亡Bax蛋白的表达常见于软组织肉瘤（STS），且在不同肿瘤中常与化学敏感性相关。关于凋亡相关标志物Bcl-2和Bax在STS中的临床意义的研究有限。在本研究中，对86例多种类型的成人肢体STS组织芯片进行了Bcl-2和Bax的免疫组织化学检测。在25.9%和66.7%的肉瘤中分别检测到Bcl-2和Bax阳性表达。Bcl-2和Bax的过表达均与组织学分级和临床分期直接相关。还观察到Bax和Bcl-2表达之间存在显著关联（P = 0.007）。该组的5年总生存率为57%，Bcl-2过表达的病例（47.6%对58.3%）和Bax过表达的病例（50%对66.7%）的生存率较低，尽管无统计学意义。多因素分析后，仅高组织学分级是患者的独立预后因素（P = 0.043；HR = 8.0；95% CI，1.1 - 60.1）。在我们的研究中，Bcl-2和Bax表达与组织学分级和临床分期显著相关，而组织学分级和临床分期是预后不良的经典因素。我们建议将这些蛋白用作肢体STS潜在的预后标志物。
