Kaseta Maria-Kyriaki A, Khaldi Lubna, Gomatos Ilias P, Tzagarakis George P, Alevizos Leonidas, Leandros Emmanuel, Papagelopoulos Panayiotis J, Soucacos Panayiotis N
First Department of Orthopaedic Surgery, KAT Hospital, University of Athens, Athens, Greece.
J Surg Oncol. 2008 Mar 1;97(3):259-66. doi: 10.1002/jso.20913.
To investigate the immunohistochemical expression of three apoptosis-related genes (bax, bcl-2, and p53) and apoptosis (TUNEL) in patients with primary osteosarcoma, and examine potential correlations between gene expression and clinicopathological characteristics in these patients.
Thirty-five primary osteosarcoma specimens and 18 tissue specimens deriving from non-malignant osseous lesions were immunohistochemically stained for bax, bcl-2, and p53 proteins, while apoptosis was investigated by the TUNEL method. The results were statistically analyzed.
P53, bax, and bcl-2 protein expression was observed in 22 (62.9%), 29 (82.9%), and 18 (51.4%) osteosarcoma patients, respectively. Non-specific positive TUNEL staining (+/-) was observed in two primary osteosarcoma cases (5.7%). None of the benign controls expressed any of the genes studied. None of the apoptosis-related genes studied was able to predict overall or disease-free survival in our group of patients. Nevertheless, increased bax/bcl-2 protein expression ratio was associated with a decreased 4-year survival and disease free survival (P = 0.0229 and P = 0.0370, respectively). Furthermore, all the patients who were bax(+)/bcl-2(-)/p53(+) relapsed within the 4-year follow-up period (P = 0.0385).
The increased apoptotic rate as determined by an elevated bax/bcl-2 protein expression ratio or by the bax(+)/bcl-2(-)/p53(+) protein expression pattern, appears to identify groups of osteosarcoma patients with unfavorable prognosis.
研究原发性骨肉瘤患者中三种凋亡相关基因(bax、bcl-2和p53)的免疫组化表达及凋亡情况(TUNEL法),并探讨这些患者基因表达与临床病理特征之间的潜在相关性。
对35例原发性骨肉瘤标本和18例非恶性骨病变组织标本进行bax、bcl-2和p53蛋白的免疫组化染色,同时采用TUNEL法检测凋亡情况。对结果进行统计学分析。
骨肉瘤患者中p53、bax和bcl-2蛋白表达分别见于22例(62.9%)、29例(82.9%)和18例(51.4%)。2例原发性骨肉瘤病例(5.7%)观察到非特异性TUNEL阳性染色(+/-)。良性对照均未表达所研究的任何基因。在所研究的凋亡相关基因中,无一能够预测本组患者的总生存期或无病生存期。然而,bax/bcl-2蛋白表达比值升高与4年生存率和无病生存率降低相关(分别为P = 0.0229和P = 0.0370)。此外,所有bax(+)/bcl-2(-)/p53(+)的患者在4年随访期内均复发(P = 0.0385)。
由升高的bax/bcl-2蛋白表达比值或bax(+)/bcl-2(-)/p53(+)蛋白表达模式所确定的凋亡率升高,似乎可识别出预后不良的骨肉瘤患者群体。