Vrabie Camelia Doina, Ceauşu M, Petrescu Angela, Waller Maria, Dina I
"Victor Babeş" National Institute for Research and Development in Pathology and Biomedical Sciences, Bucharest, Romania.
Rom J Morphol Embryol. 2008;49(4):525-35.
Colorectal cancer is an important disease with a large morbidity and mortality and also with increasing health care costs because of widespread of the multi-modal therapy and of the new drugs that continue to appear. There are 678.000 colorectal cancer cases and 400.000 deaths from the disease worldwide. It is the second commonest cause of cancer death in the European Union but, unlike the commonest cause of cancer related death that is lung cancer, the basis of the disease initiation is currently not understood. At the same time, the incidence increases with age, the carcinomas being rare before the age of 40 years, excepting individuals with genetic predisposition or predisposing conditions such as inflammatory bowel diseases. The early detection of colorectal cancer is potential associated with an important decrease of the cancer related mortality.
Our study proposes to find out the significance of some immunohistochemical markers (VEGF, p53, CK20 and CEA) in sporadic colorectal carcinoma cases and to establish the statistical correlations between molecular markers and tumor grade and stage.
We investigated histopathological 40 inpatients (19 female and 21 males) who undergone surgery for colorectal carcinomas in "Sf. Ioan" Emergency Hospital, Bucharest, between September 2005-September 2006. We proceeded the histopathological examination to establish the grade, stage and the main features of the tumors, and then we analyzed using ABC method for immunohistochemistry the following markers for 20 selected cases: vascular endothelial growth factor (VEGF), carcinoembrionic antigen (CEA), cytokeratin 20 (CK20), and p53 oncoprotein. Finally, we analyzed statistical the results using t-Student test.
The distribution of colorectal cancer cases (n = 40) regarding the age has showed the preponderance of patients older than 70 years (22/55%) and a small percentage of younger adults (2/5%). The repartition of colorectal tumors of sex ratio outlines a small difference between males (21/52.5%), and females (19/47.5%). The histopathological analysis of tumor grade in the 40 cases has revealed a high percent of moderate grade tumors (23/57.5%), in comparison with the poor differentiated tumors (11/27.5%) and the well-differentiated cancers (6/15%). The neovascularity within the stroma, the main features of tumor growth, has been noticed in 15 cases (3.75%), and also an important inflammatory lymphocyte infiltrate in nine cases (22.5%). We have noticed positive correlation between VEGF1 and CK20 (r = 0.4, p = 0.05), and between VEGF1 and CEA (r = 0.88, p = 0.001). In addition, our results demonstrate a positive correlation between tumor grade and CEA (r = 0.43, p = 0.009), and no relation among the other markers.
Our present study shows that CK20 and CEA are positive immunostaining markers no matter the stage (100%). The oncoprotein p53 has been negative in T1 and T2 stages, but in advanced stages has been positive in a half of cases (50%). Regarding the location, p53 and VEGF showed positively results whatever the topography. We have noticed a direct proportional relation in VEGF expression and CEA, and CEA and tumor grade (r = 0.88, p<0.001).
结直肠癌是一种重要疾病，发病率和死亡率都很高，而且由于多模式治疗的广泛应用以及不断出现的新药，医疗保健成本也在增加。全球有67.8万例结直肠癌病例，40万人死于该疾病。它是欧盟癌症死亡的第二大常见原因，但与最常见的癌症相关死亡原因肺癌不同，目前尚不清楚该疾病的发病基础。同时，发病率随年龄增长而增加，除了有遗传易感性或诸如炎症性肠病等易感疾病的个体外，40岁之前癌症很少见。结直肠癌的早期检测可能与癌症相关死亡率的显著降低有关。
我们的研究旨在找出某些免疫组化标志物（血管内皮生长因子（VEGF）、p53、细胞角蛋白20（CK20）和癌胚抗原（CEA））在散发性结直肠癌病例中的意义，并建立分子标志物与肿瘤分级和分期之间的统计相关性。
我们调查了2005年9月至2006年9月期间在布加勒斯特“圣约安”急诊医院接受结直肠癌手术的40例住院患者（19名女性和21名男性）的组织病理学情况。我们进行组织病理学检查以确定肿瘤的分级、分期和主要特征，然后对20例选定病例使用免疫组化ABC法分析以下标志物：血管内皮生长因子（VEGF）、癌胚抗原（CEA）、细胞角蛋白20（CK20）和p53癌蛋白。最后，我们使用t检验对结果进行统计学分析。
40例结直肠癌病例的年龄分布显示，70岁以上患者占多数（22/55%），年轻成年人比例较小（2/5%）。结直肠肿瘤的性别比例分布显示男性（21/52.5%）和女性（19/47.5%）之间存在微小差异。对40例病例的肿瘤分级进行组织病理学分析发现，中度分级肿瘤的比例很高（23/57.5%），相比之下，低分化肿瘤（11/27.5%）和高分化癌症（6/15%）。在15例（3.75%）病例中发现基质内有新生血管，这是肿瘤生长的主要特征，在9例（22.5%）病例中还发现有重要的炎性淋巴细胞浸润。我们注意到VEGF1与CK20之间呈正相关（r = 0.4，p = 0.05），VEGF1与CEA之间呈正相关（r = 0.88，p = 0.001）。此外，我们的结果表明肿瘤分级与CEA之间呈正相关（r = 0.43，p = 0.009），其他标志物之间无相关性。
我们目前的研究表明，无论处于何阶段，CK20和CEA都是阳性免疫染色标志物（100%）。癌蛋白p53在T1和T2期为阴性，但在晚期有一半病例（50%）为阳性。关于位置，无论处于何种部位，p53和VEGF均呈阳性结果。我们注意到VEGF表达与CEA以及CEA与肿瘤分级之间存在正比关系（r = 0.88，p<0.001）。
