【作者】 孙发政；

【导师】 卢兆桐；

【作者基本信息】 泰山医学院 ， 外科学， 2009， 硕士

【摘要】 目的:本研究以原发性肺癌患者为研究对象,在蛋白质水平探讨CD10、CD13和CTAg作为特异性肿瘤标记物对原发性肺癌的诊断、鉴别诊断、判断病情进展及预后的临床价值。方法:收集原发性肺癌病例73例,其中包括鳞癌27例,腺癌30例,小细胞肺癌16例,采用免疫组织化学方法分别检测CD10、CD13和CTAg在上述病例手术切除标本中的表达,并与癌旁组织、26例肺良性肿瘤、20例正常肺组织进行比较。结果:1、CD10的表达:①在73例肺癌标本中CD10表达阳性率为32.88%(24/73),肺良性肿瘤阳性率88.46%(23/26),正常肺组织阳性率95.00%(19/20),CD10在肺癌中的表达明显低于肺良性肿瘤及正常肺组织(P＜0.001)。②73例肺癌间质细胞CD10阳性率63.01%(46/73),癌旁组织阳性率94.52%(69/73),CD10在肺癌间质细胞中的表达明显低于在正常肺组织、癌旁组织中的表达(P＜0.001)。③腺癌、鳞癌、小细胞癌中CD10表达阳性率为分别为50%(15/30)、22.22%(6/27)、18.75%(3/16),肺癌临床Ⅰ、Ⅱ、Ⅲ～Ⅳ中CD10表达阳性率分别为73.33%(11/15)、22.22%(4/18)、22.50%(9/40),肺癌高、中、低分化中CD10表达阳性率分别为71.43%(5/7)、38.71%(12/31)、20.00%(7/35),有无淋巴结转移中CD10表达阳性率分别为21.95%(9/41)、46.87%(15/32)。CD10在肺癌中的表达与肺癌病理分型、临床分期、组织分化程度及淋巴结转移有相关性(P＜0.05)。2、CD13的表达:①在73例肺癌标本中CD13表达阳性率为41.10%(30/73),肺良性肿瘤阳性率15.38%(4/26),正常肺组织组阳性率5%(1/20),CD13在肺癌中表达明显高于肺良性肿瘤及正常肺组织(P＜0.05)。②73例肺癌间质细胞CD13阳性率36.98%(27/73),癌旁组织阳性率17.81%(13/73),CD13在肺癌间质细胞中的表达明显高于癌旁肺组织及正常肺组织(P＜0.05)。③腺癌、鳞癌、小细胞癌中CD13表达阳性率为分别为70%(21/30)、29.63%(8/27)、6.25%(1/16)。肺癌临床Ⅰ、Ⅱ、Ⅲ-Ⅳ中CD13表达阳性率分别为6.67%(1/15)、52.50%(21/40)、44.44%(8/18)。肺癌高、中、低分化中CD13表达阳性率分别为14.29%(1/7)、60.00%(21/35)、25.81%(8/31)。有无淋巴结转移中CD13表达阳性率分别为60.98%(25/41)、15.63%(5/32)。CD10在肺癌中的表达与肺癌病理分型、临床分期、组织分化程度及淋巴结转移有相关性(P＜0.05)。3、CTAg的表达:①73例肺癌标本中,NY-ESO-1阳性表达33例,阳性率45.21%(33/73),MAGE-A1阳性表达41例,阳性率56.16%(41/73),癌旁组织、肺良性肿瘤、正常肺组织中均无NY-ESO-1和MAGE-1表达。②腺癌、鳞癌、小细胞癌中NY-ESO-1表达阳性率为分别为70%(21/30)、33.33%(9/27)、18.75%(3/16),MAGE-A1表达阳性率为分别为83.33%(25/30)、25.93%(7/27)、56.25%(9/16)。肺癌临床Ⅰ、Ⅱ、Ⅲ-Ⅳ中NY-ESO-1表达阳性率分别为26.67%(4/15)、27.78%(5/18)、60.00%(24/40),MAGE-A1表达阳性率为分别为60.00%(9/15)、61.11%(11/18)、52.50%(21/40)。肺癌高、中、低分化中NY-ESO-1表达阳性率分别为28.57%、29.03%(9/31)、62.86%(22/35),MAGE-A1表达阳性率为分别为42.86%(3/7)、35.48%(11/31)、77.14%(27/35)。有无淋巴结转移中NY-ESO-1表达阳性率分别为56.98%(23/41)、31.25%(10/32),MAGE-A1表达阳性率为分别为53.66%(22/41)、59.38%(19/32)。NY-ESO-1在肺癌中的表达与肺癌病理分型、临床分期、组织分化程度及淋巴结转移有相关性(P＜0.05)。MAGE-A1在肺癌中的表达与肺癌病理分型、组织分化程度有相关性(P＜0.05),与临床分期、淋巴结转移无明显相关性(P＞0.05)。结论:1、CD10在肺癌细胞、肿瘤间质细胞中的表达显著降低,CD10可以作为有价值的肿瘤标记物用于肺癌的诊断和鉴别诊断。CD10的表达与肺癌患者的年龄、病理分型、组织分化程度、临床分期、淋巴结转移有相关性,对肺癌的预后判断有指导意义。2、CD13在肺癌细胞、肿瘤间质细胞呈高表达,CD13可以作为一种独立肿瘤标记物应用于肺癌的诊断和鉴别诊断。CD13的表达与肺癌患者的病理分型、组织分化程度、临床分期、淋巴结转移均有明显相关性,对肺癌的预后判断有指导意义。3、NY-ESO-1和MAGE-A1在癌旁组织、肺良性肿瘤、正常肺组织中均无表达,只在肺癌中特异性表达,是特异性肺癌标记物。NY-ESO-1的表达与肺癌患者的病理分型、组织分化程度、临床分期、淋巴结转移有明显相关性。4、四种抗原都具有较强特异性,但单独表达的敏感性相对较差,联合检测,起到互补作用,可以从不同的侧面,较全面地反映肿瘤细胞的生物学特性,对肺癌的诊断、鉴别诊断、治疗效果的评价,预后的判断有着重要的指导意义。更多还原

【Abstract】 Objective:To investigate the relationship that expression of CD10,CD13 and CTAg in protein level as a specific tumor marker to diagnosis,differential diagnosis,disease prediction and prognosis of primary pulmonary carcinoma.Methods:In 73 cases of primary pulmonary carcinoma,including 27 cases of squamous cell carcinoma,30 cases of adenocarcinoma,16 cases of small cell lung cancer, the CD10,CD13 and CTAg expression were detected by means of immunohistochemistry and were compared with adjacent lung tissues,26 pulmonary benign tumors,20 cases of normal lung tissue.Results:1、The expression of CD10:①24 of 73 cases of pulmonary carcinoma were CD10 positive(32.88%),and 23 of 26 eases of pulmonary benign tumors were CD10 positive(88.46%).19 of 20 eases of common lungs were CD10 positive(95%).The positive expression of CD10 in pulmonary carcinoma was significantly lower than in pulmonary benign tumors and common lung(P＜0.05).②46 of 73 cases of pulmonary carcinoma stromal cells were CD10 positive(63.01%),69 of 73 cases of lung cancer adjacent tissues were CD10 positive(94.52%),CD10 positive rates in lung cancer stromal cells was significantly lower than in normal lung tissue,cancer adjacent tissues(P＜0.001).③The positive expression of CD10 in lung adenocarcinoma,squamous cell carcinoma,small cell carcinoma were50%(15/30)、22.22%(6/27)、18.75%(3/16) respectively。The positive expression of CD10 in clinical stageⅠ、Ⅱ、Ⅲ～Ⅳwere 73.33%(11/15)、22.22% (4/18)、22.50%(9/40) respectively。The positive expression of CD10 in well, moderately and poorly differentiated pulmonary carcinoma were 71.43%(5/7)、38.71% (12/31)、20.00%(7/35) respectively.It was also shown the positive expression of CD10 in cases with lymph node metastasis(21.95%) was markedly lower than that in those without lymph node metastasis(46.87%).The expression of CD10 was related to pathological classification of lung cancer,clinical stage,pathological differentiation and lymph node metastasis(P＜0.05).2、The expression of CD13:①30 of 73 cases of pulmonary carcinoma were CD13 positive(41.10%),and 4 of 26 eases of pulmonary benign tumors were CD13 positive(15.38%).1 of 20 eases of common lungs were CD13 positive(5%).The positive incidence of CD13 in pulmonary carcinoma was significantly lower that in pulmonary benign tumors and 20 cases of common lung(P＜0.05).②27 of 73 cases of lung cancer stromal cells were CD13 positive(36.98%),13 of 73 cases of lung cancer adjacent tissues were CD10/NEP positive(17.81%),CD13 positive in lung cancer stromal cells was significantly lower than in normal lung tissue,cancer adjacent tissues(P＜0.05).③The positive expression of CD 13 in lung adenocarcinoma,squamous cell carcinoma,small cell carcinoma were 70%(21/30)、29.63%(8/27)、6.25%(1/16 ) respectively。The positive expression of CD13 in clinical stageⅠ、Ⅱ、Ⅲ～Ⅳwere 6.67%(1/15)、52.50%(21/40)、44.44%(8/18) respectively.The positive expression of CD13 in well、moderately and poorly differentiated pulmonary carcinoma were 14.29%(1/7)、60.00%(21/35)、25.81% (8/31) respectively.It was also shown the positive expression of CD13 in cases with lymph node metastasis(60.98%) was markedly higher than that in those without lymph node metastasis(15.63%)。The expression of CD13 was related to pathological classification of lung cancer,clinical stage,pathological differentiation and lymph node metastasis(P＜0.05).3、The expression of CTAg:①33 of 73 cases of pulmonary carcinoma were NY-ESO-1 positive(45.21%),41 of 73 cases of pulmonary carcinoma were MAGE-A1 positive(56.16%),Adjacent tissues,pulmonary benign tumors,normal lung tissues had no NY-ESO-1 and MAGE-1 expression.②The positive expression of NY-ESO-1 in lung adenocarcinoma,squamous cell carcinoma,small cell carcinoma were 70%(21/30)、33.33%(9/27)、18.75%(3/16) respectively.The positive rates of MAGE-A1 were83.33 %(25/30)、25.93%(7/27)、56.25%(9/16).The positive expression of NY-ESO-1 in clinical stageⅠ、Ⅱ、Ⅲ～Ⅳwere 26.67%(4/15)、27.78%(5/18)、60.00%(24/40).The positive rates of MAGE-A1 were60.00%(9/15)、61.11%(11/18)、52.50%(21/40) respectively.The positive expression of NY-ESO-1 in well、moderately and poorly differentiated pulmonary carcinoma were 28.57%、29.03%(9/31)、62.86%(22/35) respectively.The positive rates of MAGE-A1 were42.86%(3/7)、35.48%(11/31)、77.14%(27/35).It was also shown the positive expression of NY-ESO-1 in cases with lymph node metastasis(56.98%) was markedly higher than that in those without lymph node metastasis(31.25%).The expression of NY-ESO-1 was related to pathological classification of lung cancer,clinical stage,pathological differentiation and lymph node metastasis(P＜0.05).The expression of MAGE-A1 was also related to Pathological classification of lung cancer and pathological differentiation(P＜0.05),however, expression rate of MAGE-1 has no relationship with clinical stage,lymph node metastasis(P＞0.05).Conclusion:1、CD10 protein expression was markedly reduced or completely absent in pulmonary carcinoma,tumor stromal cells.CD10 can serve as a valuable tumor marker for lung cancer diagnosis and differential diagnosis.There was correlation between loss of CD10 expression and most clinicopathologic parameters including age,pathological type, differentiation,clinical stage,lymph node metastasis.Diminished or even loss of CD10 expression may be important in the pulmonary carcinogenesis.2、CD13 protein expression was markedly increased in pulmonary carcinoma,tumor stromal cells.CD13 can serve as a valuable tumor marker for lung cancer diagnosis and differential diagnosis. There was correlation between loss of CD13 expression and most clinicopathologic parameters including pathological type,differentiation,clinical stage,lymph node metastasis.Raise of CD13 expression may be important in the pulmonary carcinogenesis. 3、NY-ESO-1 and MAGE-A1 are expressed only in pulmonary carcinoma and not in the adjacent tissues,lung benign tumor,normal lung tissues.The expression of NY-ESO-1 was related to pathological classification of lung cancer,clinical stage,pathological differentiation and lymph node metastasis.The expression of MAGE-A1 was also related to pathological classification of lung cancer and pathological differentiation,however, expression rate of MAGE-1 has no relationship with clinical stage,lymph node metastasis. 4、A combination of these four markers:CD10,CD13,NY-ESO-1 and MAGE-A1,is helpful in the differential diagnosis of pulmonary carcinoma.更多还原