肿瘤干细胞相关标志蛋白在眼眶腺样囊性癌中的表达分析

目的 观察肿瘤干细胞相关标志蛋白CD44、CD133和ABCG2在眼眶腺样囊性癌中的表达,分析其与肿瘤的病理分型、预后之间的关系.方法 实验研究.选取1991年1月至2009年3月间,手术切除后病理证实为眼眶腺样囊性癌的患者中,具有详细随访记录的,首次切除的肿瘤组织石蜡包埋标本33例,复发后切除的肿瘤组织标本5例.ACC-2细胞系建立的裸鼠眼眶移植瘤模型标本6例,以3例正常泪腺组织标本作为对照,采用二步法免疫组织化学法检测CD44、CD133、ABCG2在标本中的表达.分析其与临床病例资料中病理分型、预后的关系.统计学方法采用Fish精确检验,两组间关系比较运用Spearman等级相关检验.结果 CD44表达阳性率为54.5%(18/33).实体型阳性率76.9%(10/13),多呈片状散在分布于肿瘤边缘浸润灶,肿瘤细胞密集处没有着染;筛网型为40.0%(8/20),多分布在肌上皮细胞,二者差异无统计学意义(P=0.072);正常泪腺组织中CD44也有阳性表达.CD133阳性表达率为57.6%(19/33),实体型和筛网型分别为76.9%(10/13)、45.0%(9/20),差异无统计学意义(P=0.087);表达产物定位于细胞膜和细胞质,但部分病例同时表达于胞质和胞核.ABCG2表达阳性率为21.2%(7/33),具有沿血管分布的倾向,实体型和筛网型分别为30.8%(4/13)、15.0%(3/20),差异无统计学意义(P=0.393).CD44、CD133及ABCG2在无复发组的表达阳性率均低于复发组,预后好组低于预后差组,但差异均无统计学意义(P＞0.05).CD44和CD133的阳性表达之间存在正相关(Spearman,rs=0.416,P=0.016).在6例荷瘤裸鼠肿瘤组织标本中,CD44阳性1例,CD133表达阳性1例,ABCG2表达阳性4例.结论 眼眶腺样囊性癌肿瘤组织中存在CD44、CD133及ABCG2阳性细胞,分别表达于腺样囊性癌肿瘤组织的不同部位,其表达随着病程进展而变化,可能会影响预后,但尚不能确定为评估预后的指标.

Abstract：

Objective To observe the expression and distribution of CD44,CD133,and ABCG2 in orbital adenoid cystic carcinoma (ACC) and investigate their correlations with pathological type and prognosis. Method Two steps method of immunohistochemical staining was employed in 33 cases of paraffin embedded surgical specimens of human orbital ACC,5 cases of recurrence samples,3 cases of an excised lacrimal gland caused by neither inflammation nor tumor diseases,and 6 cases of xenograft tumors in nude mice. A retrospective analysis was performed on the clinical material of these patients,which were collected from Jan. 1991 to Mar. 2009. Results The positive rate of CD44 was 54. 5% ( 18/33),with 76. 9% (10/13) in solid type and 40. 0% (8/20) in adeno-tubiform type. There was no statistically significant difference between them (P = 0. 072). In solid type the positive expression cells were often located at the marginal part of the cancer nest. In the adeno-tubiform type,positive cells were often located at the outer layer of the tubiform structure ( myoepithelial cells). CD44 was also expressed in normal tissues.The positive rate of CD133 was 57.6% (19/33),with 76. 9% (10/13) in solid type and 45.0% (9/20)in adeno-tubiform type. There was no significant difference between them (P =0. 087). CD133 antigen was expressed in either the cytoplasm or nucleus,or expressed in both the cytoplasm and nucleus. The positive rate of ABCG2 was 21.2% (7/33),with 30. 77% (4/13) in solid type and 15.0% (3/20) in adenotubiform type. There was no significant difference between them ( P = 0. 393 ) . Many positive cells surrounded the vessels in tumor tissues. There were no significant differences between different prognosis groups of these surface phenotypes. The correlative analysis results of three surface phenotypes showed that CD44 + cells have positive correlation with CD133 + cells ( Spearman,rs = 0. 416,P = 0. 016 ). In six transplanted tumors of nude mice,the number of positive cases for CD44 +,CD133 + and ABCG2 + was 1,1 and 4 cases,respectively. Conclusions The expression of CD44,CD133 and ABCG2 in ACC may influence the progress of ACC. However,they cannot be used as the markers for the evaluation of the prognosis of this tumor.

Analysis of expression of cancer stem cell-related markers in orbital adenoid cystic carcinoma

Objective To observe the expression and distribution of CD44,CD133,and ABCG2 in orbital adenoid cystic carcinoma (ACC) and investigate their correlations with pathological type and prognosis. Method Two steps method of immunohistochemical staining was employed in 33 cases of paraffin embedded surgical specimens of human orbital ACC,5 cases of recurrence samples,3 cases of an excised lacrimal gland caused by neither inflammation nor tumor diseases,and 6 cases of xenograft tumors in nude mice. A retrospective analysis was performed on the clinical material of these patients,which were collected from Jan. 1991 to Mar. 2009. Results The positive rate of CD44 was 54. 5% ( 18/33),with 76. 9% (10/13) in solid type and 40. 0% (8/20) in adeno-tubiform type. There was no statistically significant difference between them (P = 0. 072). In solid type the positive expression cells were often located at the marginal part of the cancer nest. In the adeno-tubiform type,positive cells were often located at the outer layer of the tubiform structure ( myoepithelial cells). CD44 was also expressed in normal tissues.The positive rate of CD133 was 57.6% (19/33),with 76. 9% (10/13) in solid type and 45.0% (9/20)in adeno-tubiform type. There was no significant difference between them (P =0. 087). CD133 antigen was expressed in either the cytoplasm or nucleus,or expressed in both the cytoplasm and nucleus. The positive rate of ABCG2 was 21.2% (7/33),with 30. 77% (4/13) in solid type and 15.0% (3/20) in adenotubiform type. There was no significant difference between them ( P = 0. 393 ) . Many positive cells surrounded the vessels in tumor tissues. There were no significant differences between different prognosis groups of these surface phenotypes. The correlative analysis results of three surface phenotypes showed that CD44 + cells have positive correlation with CD133 + cells ( Spearman,rs = 0. 416,P = 0. 016 ). In six transplanted tumors of nude mice,the number of positive cases for CD44 +,CD133 + and ABCG2 + was 1,1 and 4 cases,respectively. Conclusions The expression of CD44,CD133 and ABCG2 in ACC may influence the progress of ACC. However,they cannot be used as the markers for the evaluation of the prognosis of this tumor.