Armistead Paul M, Salganick Jason, Roh Jae S, Steinert Dejka M, Patel Shreyaskumar, Munsell Mark, El-Naggar Adel K, Benjamin Robert S, Zhang Wei, Trent Jonathan C
Department of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2007 Nov 15;110(10):2293-303. doi: 10.1002/cncr.23038.
Rhabdomyosarcoma (RMS) is a rare mesenchymal tumor with few treatment options after the failure of first-line therapy. Understanding the expression of kinases and apoptotic molecules in RMS tumors may lead to elucidation of mechanisms of resistance to chemotherapy and development of new therapies.
Paraffin-embedded tissue samples were collected from 105 RMS patients treated at the M. D. Anderson Cancer Center and examined for the immunohistochemical expression of kinases and apoptotic molecules deemed potential therapeutic targets. Clinicopathologic information was collected on all patients and analyzed for correlation with overall survival (OS).
Of the 105 patients, 44 (42%) were female and 89 (85%) were older than 10 years of age. The 5-year OS for this cohort was 24.7%, with inferior median OS in patients with genitourinary primary tumors and those with invasion through the deep fascial plane. Immunohistochemistry revealed Kit and c-erb-b2 to be present on < 10% of tumors but EGFR, PDGFR-alpha, PDGFR-beta, Bcl-2, and Bax were present in > 40% of tumors. Patients whose tumors expressed PDGFR-alpha were found to have a shorter median OS by multivariate analysis (26 vs 266 months, P = .076). Conversely, patients whose tumors expressed Bax were found to have a longer OS (31 vs 19 months, P = .047).
EGFR, PDGFR-alpha, PDGFR-beta, Bcl-2, and Bax are frequently expressed in human RMS tissue and may represent new therapeutic targets. Absence of PDGFR-alpha and the presence of Bax are associated with a longer median OS in patients with RMS. Targeting these molecules may be a successful therapeutic strategy.
横纹肌肉瘤（RMS）是一种罕见的间叶组织肿瘤，一线治疗失败后治疗选择有限。了解RMS肿瘤中激酶和凋亡分子的表达情况可能有助于阐明化疗耐药机制并开发新的治疗方法。
收集了在MD安德森癌症中心接受治疗的105例RMS患者的石蜡包埋组织样本，检测了被认为是潜在治疗靶点的激酶和凋亡分子的免疫组化表达。收集了所有患者的临床病理信息，并分析其与总生存期（OS）的相关性。
105例患者中，44例（42%）为女性，89例（85%）年龄大于10岁。该队列的5年总生存率为24.7%，泌尿生殖系统原发性肿瘤患者和穿透深筋膜平面的患者中位总生存期较差。免疫组化显示，<10%的肿瘤表达Kit和c-erb-b2，但>40%的肿瘤表达表皮生长因子受体（EGFR）、血小板衍生生长因子受体α（PDGFR-α）、血小板衍生生长因子受体β（PDGFR-β）、B细胞淋巴瘤/白血病-2（Bcl-2）和Bax。多因素分析发现，肿瘤表达PDGFR-α的患者中位总生存期较短（26个月对266个月，P = 0.076）。相反，肿瘤表达Bax的患者总生存期较长（31个月对19个月，P = 0.047）。
EGFR、PDGFR-α、PDGFR-β、Bcl-2和Bax在人RMS组织中频繁表达，可能代表新的治疗靶点。RMS患者中，PDGFR-α缺失和Bax存在与较长的中位总生存期相关。靶向这些分子可能是一种成功的治疗策略。
