消化道肿瘤原发灶及转移淋巴结survivin、bcl-2表达与化疗药敏性的关系

Relationship between Expression of survivin, bcl-2 and Chemosensitivities in Lymph Node Metastases Compared with Gastrointestinal Primary Tumor

目的探讨消化道肿瘤原发灶及转移淋巴结survivin、bcl-2表达的变化及其与化疗药敏性的关系。方法对54例胃癌和大肠癌肿瘤组织、转移淋巴结分别进行细胞培养化疗药敏性实验及survivin、bcl-2免疫组化染色,对比研究两种病灶的实验结果。结果(1)原发、转移灶survivin表达一致率较低,为24.1%(k=-0.0634,P=0.4392);survivin、bcl-2在原发灶与转移淋巴结间表达强度无明显差异(Z=3.5、9.5,均P>0.05);bcl-2在原发灶与转移淋巴结中表达具有明显相关性(r=0.5226,P<0.05),原发灶中survivin与bcl-2表达具有正相关性(r=0.2937,P=0.0311)。(2)11种化疗药物对原发灶、转移灶肿瘤细胞的平均抑制率不同。HCPT、LOHP、CDDP、MTX、VCR对转移淋巴结细胞抑制率均明显低于原发灶(t=-2.08～-2.48,均P<0.05),VP-16、THP、MMC对原发灶的抑制率明显低于转移灶(t=2.11～3.06,均P<0.05)。③在原发灶及转移灶中,survivin表达程度分别与VCR和VP-16、PTX的抑制率呈负相关(r=-0.4135及r=-0.4061、-0.5127;均P<0.05);而bcl-2表达程度则分别与5-Fu、PTX和VP-16、HCPT、PTX、LOHP、eADM的抑制率呈负相关(r=-0.4715、-0.3965及r=-0.4002～-0.5644;均P<0.05)。结论消化道肿瘤淋巴结转移灶在凋亡抑制蛋白表达程度及对化疗药敏性方面均呈现与原发灶不同的异质性,术后辅助化疗靶目标应针对淋巴结转移灶。

Objective To investigate the relationship between expression of survivin or bcl-2 and chemosensitivities in lymph node metastases （LNMs） and gastrointestinal carcinomas. Methods The chemosenisitivities of tumor cells to 11 drugs were measured by MTT assay, and expression of survivin and bcl-2 were determined immunohistochemically in 54 paired primary tumor （PT） and LNMs of gastrointestinal carcinomas. Results The low accordance （24.1%） in expression of survivin was observed between PT and LNMs（k =-0. 0634, P = 0. 4392）. There was no significant difference in either expression of survivin or bcl-2 between PT and LNMs （Z= 3. 5, 9. 5; both P〉0. 05）. The expression of bcl-2 showed a positive correlation between LNMs and PT （r = 0. 5226, P〈0.05）. In PT, survivin expression showed positive correlation with bcl-2 （r= 0. 2937,P=0.0311）. The inhibition rates of LNMs cells for HCPT, LO- HP, CDDP, MTX and VCR were lower than those of PT （t=-2.08--2. 48, all P〈0. 05）, and for higher VP-16, THP and MMC were detected （t = 2. 11 -3. 06, all P〈0. 05）. There was statistically negative correlativity between expression of survivin and inhibition rates of PT for VCR （r = -0. 4135, P〈0. 05）, and of LNMs for VP-16 and PTX （r = -0. 4061, -0. 5127; both P%0. 05） respectively. Expression of bcl-2 in PT was negative correlation with inhibition rates for 5-Fu and PTX （r = -0. 4715, 0. 3965; both P〈0. 05） , and also in LNMs for VP-16, HCPT , PTX, LOHP and eADM （r=-0. 4002 --0. 5644; all P〈0. 05）. Conclusion The LNMs of gastrointestinal carcinomas are heterogeneous with respect to the expression of anti-apoptosis proteins and response to chemotherapy. Effective adjuvant chemotherapy in gastrointestinal cancers depends on targeting the metastatic component of the disease.