CEA和P53及Ki67在肺腺体前驱病变及微浸润性腺癌中的表达及临床价值

Expressions and clinical value of CEA, P53 and Ki67 in lung precursor glandular lesions and minimally invasive adenocarcinoma

摘要

目的 探讨癌胚抗原(carcinoembryonic antigen, CEA)、P53及Ki67在肺腺体前驱病变[非典型腺瘤样增生(atypical adenomatous hyperplasia, AAH)和原位腺癌(adenocarcinoma in situ, AIS)]、微浸润性腺癌(minimally invasive adenocarcinoma, MIA)发生中的作用及病理诊断价值。方法 收集AAH 16例、AIS 8例、MIA 16例,采用免疫组化EnVision技术检测CEA、P53及Ki67表达,分析其与临床病理参数的相关性及诊断效能。结果 在AAH、AIS、MIA中,CEA的表达率分别为87.5%、87.5%、93.8%,其表达率逐渐升高,表达强度逐渐增强,差异具有统计学意义(P＜0.01)。AAH组P53表达突变型百分率为18.8%,表达野生型百分率为81.2%;AIS组P53表达突变型百分率为37.5%,表达野生型百分率为62.5%;MIA组P53表达突变型百分率为75.0%,表达野生型百分率为25.0%。P53突变的发生率随着病变的进展逐渐升高,差异具有统计学意义(P＜0.01)。在16例肺AAH中,Ki67呈低表达的百分率为75.0%,中表达的百分率为25.0%,无高表达。在8例肺AIS中,Ki67呈低表达的百分率为50.0%,中表达的百分率为12.5%,高表达的百分率为37.5%。在16例MIA中,Ki67呈低表达的百分率为25.0%,中表达的百分率为62.5%,高表达的百分率为12.5%,随着病变进展其表达水平逐渐升高,差异具有统计学意义(P＜0.05)。ROC曲线分析显示,AAH、AIS及MIA中,联合检测P53、CEA、Ki67三种标志物的曲线下面积(AUC)分别为0.963、0.793、0.887,明显高于三者单一检测(P＜0.05),进一步说明联合检测可提高肺腺体前驱病变(AAH、AIS)及MIA诊断的准确性和可靠性。结论 在肺泡上皮非典型腺瘤样增生、原位腺癌进展为微浸润性腺癌过程中,P53、CEA起着重要的作用,促进肺腺癌的发生发展,可作为诊断肺腺体前驱病变及肺微浸润性腺癌较特异的分子标志物。联合检测P53、CEA、Ki67三种标志物,对早发现、早诊断肺腺癌具有重要的临床价值。

Abstract

Objective To explore the role and pathological diagnostic value of the expressions of CEA, P53, and Ki67 in lung precursor glandular lesions, including atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS), as well as minimally invasive adenocarcinoma (MIA). Methods The specimens containing 16 cases of AAH, 8 cases of AIS, and 16 cases were collected to identify the expressions of CEA, P53, and Ki67 by immunohistochemistry; their relationship with clinicopathological parameters and diagnostic efficacy were analyzed. Results The results showed that the positive rate of CEA expression was 87.5% in AAH, 87.5% in AIS, and 93.8% in MIA, respectively, with increasingly higher degree (P＜0.01). In the AAH group, the rate of P53 expression mutation was 18.8%, and the rate of wild-type expression was 81.2%. In the AIS group, the rate of P53 expression mutation and wild-type expression was 37.5% and 62.5%, respectively. In the MIA group, the rate of P53 expression mutation and wild-type expression was 75.0% and 25.0%, respectively. The incidence of P53 mutation increased with the progression of the lesion (P＜0.01). Among the 16 cases of AAH, the rate of Ki67 with low expression and with moderate expression was 75% and 25%; there was no high expression. Among the 8 cases of pulmonary AIS, the rate of Ki67 with low expression, moderate expression and high expression was 50.0%, 12.5% and 37.5%, respectively. Among the 16 cases of MIA, the rate of Ki67 with low expression, moderate expression and high expression was 25.0%, 62.5% and 12.5%, respectively. With the progression of the lesion, its expression level increased (P＜0.05). ROC curve analysis showed that the area under the curve (AUC) for the combined detection of P53, CEA and Ki67 markers in AAH, AIS and MIA was 0.963, 0.793 and 0.887, respectively, and was significantly higher when it was compared with the individual level of each marker, respectively (P＜0.05). This further shows that combined detection might improve the accuracy and reliability of diagnosing precursor glandular lesions (AAH and AIS) and MIA in lung. Conclusion The results suggest that P53 and CEA play an important role in promoting the occurrence and development of lung adenocarcinoma, during the progression from atypical adenomatous hyperplasia to in situ adenocarcinoma and then to minimally invasive adenocarcinoma in lung. Joint detection of P53 and CEA and Ki67 has significant clinical value in early detection and diagnosis of lung adenocarcinoma, and seems to be a satisfactory marker for diagnosing precursor glandular lesions and minimally invasive adenocarcinoma of the lung.

关键词

肺微浸润性腺癌 / 原位腺癌 / 非典型腺瘤样增生 / 癌胚抗原 / P53 / Ki67

Key words

minimally invasive adenocarcinoma of the lung / adenocarcinoma in situ / atypical adenomatous hyperplasia / CEA / P53 / Ki67

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