视网膜母细胞瘤高迁移率族蛋白A、MIB-1标记指数和let-7的表达及其相关性分析

The expression and relationship of high-mobility group A, MIB labeling index and let-7 in retinoblastoma

目的观察分析视网膜母细胞瘤（RB）肿瘤组织中高迁移率族蛋白A（HMGA）1和HMGA2、MIB-1标记指数（LI）及1et-7的表达及其相关性。方法44例RB肿瘤组织标本纳人研究。其中，低分化组织标本11例，高分化组织标本33例。侵袭性肿瘤组织标本8例，非侵袭性肿瘤组织标本36例。采用免疫组织化学染色方法检测RB肿瘤组织标本中HMGA1、HMGA2及MIB-1LI的表达。HMGA1、HMGA2表达判定标准：以0为无表达，1％～10％为低度表达，11％～50％为中度表达，〉50％为高度表达；MIB-1LI表达判定标准：以0为无表达，1％～40％为低度表达，〉40％为高度表达。采用逆转录聚合酶联反应检测let-7的表达；以≥80％为无明显下降，60％～79％为中度下降，〈60％为高度下降。结果44例标本中，HMGA1无表达14例，占32％；低度表达11例，占25％；中度表达10例，占23％；高度表达9例，占20％。低分化组织标本的HMGA1表达率高于高分化组织标本，差异有统计学意义（χ2=11．3，P〈0．01）。侵袭性与非侵袭性肿瘤组织标本的HMGAl表达率比较，差异无统计学意义（χ2=5．9，P〉0．05）。HMGA2无表达11例，占25％；低度表达11例，占25％；中度表达9例，占20％；高度表达13例，占30％。低分化组织标本的HMGA2表达率高于高分化组织标本，差异有统计学意义（χ2=20．9，P〈0．05）。侵袭性肿瘤组织标本的HMGA2表达率高于非侵袭性肿瘤组织标本，差异有统计学意义（χ2=8．7，P〈0．05）。MIB-1LI无表达4例，占9％；低度表达18例，占41％；高度表达22例，占50％。低分化组织标本的MIB-1LI表达水平高于高分化组织标本，差异有统计学意义（t=5．2，P〈0．05）。侵袭性肿瘤组织标本的MIB-1LI表达水平高于非侵袭性肿瘤组织标本，但差异无统计学意义（t=－1．1，P〉0．05）。1et-7表达无明显下降27例，占61％，中度下降8例，占18％，高度下降9例，占21％。相关性分析结果显示，MIB-1LI表达与HMGA1和HMGA2表达呈显著正相关（r=0．327、0．602，P〈0．05）；let-7表达与HMGA1、HMGA2表达及MIB-1LI表达均呈负相关（r=－0．247、－0．310、－0．392，P〈0．05）。结论在RB肿瘤组织中HMGA1、HMGA2和MIB-1LI均呈现高表达，let－7表达下降。1et－7有可能抑制HMGA1和HMGA2的表达。

Objective To observe the expression and relationship of high-mobility group A（HMGA） 1, HMGA2, MIB-1 labeling index （LI） and let-7 in retinoblastoma （RB）. Methods Forty-four RB samples were studied, including 11 poorly-differentiated samples, 33 well-differentiated samples; eight invasive and 36 non-invasive samples. The expression of HMGA1, HMGA2 and MIB-1 LI in RB were analyzed by immunohistochemitry. The HMGA1, HMGA2 were scored on a scale of 0 to high expression. 0： no expression; low： 1% - 10% ; medium.. 11 % - 50% ; high： 〉50%. The MIB LI were scored on a scale of 0 to high expression. 0： no expression; low.. 1% - 40%; high： 〉 40%. Semiquantitative reverse transcription-polymerase chain reaction was used to assay the let-7 expression level： ≥80% showed no significantly decreased expression;60% - 79% showed medium decrease in expression; 〈 60% highly decreased in expression. Results In 44 RB samples, there were 14 cases with no HMGA1 expression（32%）, 11 cases with low expression （25%）, 10 cases with medium expression （23%）, and nine cases with high expression （20%）. Expression level of HMGA1 was significantly higher in poorly differentiated RB than in well-differentiated RB （χ2= 11.3, P〈0.01） ; however, no statistically significant difference was found between invasive tumors and noninvasive tumors （χ2=5.9, P〉0.05）. There were 11 cases with no HMGA2 expression （25%）, 11 cases with low expression （25%）, nine cases with medium expression （20 %）, and 13 cases with high expression （30 %）. Expression level of HMGA2 was significantly higher in poorly differentiated and invasive RB than in well-differentiated and noninvasive RB respectively （χ2 = 20.9, 8.7; P〈0.05）. There were 4 cases with no MIB-1 LI expression （9%）, 18 cases with low expression （41 % ）, and 22 cases with high expression （50 %）. Expression level of MIB-1 LI was significantly higher in poorly differentiated RB than in well-differentiated RB （t=5.2, P〈0.05）. Higher expression of MIB-1 LI was found in invasive tumors than in noninvasive tumors, with no significant difference （t=- 1.1, P〉 0.05）. Twenty-seven cases had no significantly decreased expression of let-7 （61%）. There were eight cases with medium decreased expression （18%） and nine cases with highly decreased expression （21%）. Correlation analyses revealed that MIB-1 LI expression significantly correlated with HMGAland HMGA2 proteins （r=0. 327, 0. 602; P〈0.05）. A significantly inverse correlation existed between let-7 expression and HMGA1, HMGA2 proteins and MIB-1 LI respectively （r=-0.247,-0.310, -0.392; P〈0.05）. Conclusions Overexpression of HMGA1, HMGA2 and M1B-1 LI and down regulation of let-7 were demonstrated in RB. Supplying let-7 to RB cells can possibly inhibit HMGA1 and HMGA2 expression.