Zlatian Ovidiu Mircea, Comănescu Maria Victoria, Roşu Alexandra Floriana, Roşu Lucica, Cruce Mihai, Găman Alice Elena, Călina Cornelia Daniela, Sfredel Veronica
Department of Microbiology, University of Medicine and Pharmacy of Craiova, Romania;
Rom J Morphol Embryol. 2015;56(1):175-81.
Intratumoral heterogeneity implies the existence of differences between tumor cells, which can best be shown by histochemical and immunohistochemical techniques. The histological study is a mandatory step in any research aimed at characterizing tumor heterogeneity. Immunohistochemistry (IHC) also plays an important role in the differentiation of tumor types, assessing aggressiveness.
Investigated group consisted of 50 patients with colorectal adenocarcinoma, for each were recorded clinicopathological data and harvested samples intraoperatively, which were included in paraffin blocks. We perform Hematoxylin-Eosin staining for histological grade and other indices. IHC study used Avidin-Biotin-Peroxidase (ABC), with the markers: CK7, CK20, MUC1, MUC2, Ki-67, PCNA, p53, KRAS, BCL2, PTEN, EGFR. The resulting data were analyzed by statistical methods.
Most of colorectal adenocarcinoma studied had no special histological features and had G2 grade. IHC detected in most cases the CK20+÷CK7- phenotype (78%) and MUC1 (74%) protein expression. The proliferation markers (Ki-67 and PCNA) were present in all tumor mass with a variable index, which shows high intratumoral heterogeneity, but p53 and KRAS were distributed more uniformly, showing low intratumoral heterogeneity. PTEN was expressed nuclearly in 86% of the cases and EGFR in 42%.
The expression profiles of cytokeratins and mucins in the colorectal adenocarcinomas are useful in defining tumor phenotypes with different prognosis and therapy. We found a significant positive correlation between KRAS protein expression and BCL2 and TP53 expression. The study demonstrated the intratumoral and intertumoral heterogeneity, expressed at phenotypic level.
肿瘤内异质性意味着肿瘤细胞之间存在差异，这可以通过组织化学和免疫组织化学技术得到最佳体现。组织学研究是任何旨在表征肿瘤异质性的研究中的必要步骤。免疫组织化学（IHC）在肿瘤类型的鉴别、评估侵袭性方面也发挥着重要作用。
研究组由50例结肠腺癌患者组成，记录每位患者的临床病理数据并在术中采集样本，将其制成石蜡块。我们进行苏木精 - 伊红染色以确定组织学分级和其他指标。免疫组织化学研究采用抗生物素蛋白 - 生物素 - 过氧化物酶（ABC）法，使用的标志物有：CK7、CK20、MUC1、MUC2、Ki - 67、PCNA、p53、KRAS、BCL2、PTEN、EGFR。对所得数据进行统计学分析。
大多数所研究的结肠腺癌无特殊组织学特征，为G2级。免疫组织化学在大多数病例中检测到CK20 +÷CK7 - 表型（78%）和MUC1（74%）蛋白表达。增殖标志物（Ki - 67和PCNA）在所有肿瘤组织中均有表达，指数各异，显示出高度的肿瘤内异质性，但p53和KRAS分布更为均匀，显示出较低的肿瘤内异质性。PTEN在86%的病例中呈核表达，EGFR在42%的病例中表达。
结肠腺癌中细胞角蛋白和粘蛋白的表达谱有助于定义具有不同预后和治疗方案的肿瘤表型。我们发现KRAS蛋白表达与BCL2和TP53表达之间存在显著正相关。该研究证明了在表型水平上存在肿瘤内和肿瘤间异质性。
