Lewitowicz Piotr, Gluszek Stanislaw, Koziel Dorota, Horecka-Lewitowicz Agata, Chrapek Magdalena, Wolak Przemyslaw, Klusek Justyna, Nasierowska-Guttmejer Anna
Department of Pathology, Faculty of Medicine and Health Sciences, Jan Kochanowski University, Kielce, Poland.
Department of Surgery and Surgical Nursing, Faculty of Medicine and Health Sciences, Jan Kochanowski University, Kielce, Poland.
PLoS One. 2017 Feb 24;12(2):e0172381. doi: 10.1371/journal.pone.0172381. eCollection 2017.
Colorectal cancer belongs to the most frequent occurring malignancies. A prediction of the clinical outcome and appropriate choice of neoadjuvant chemotherapy needs personalized insight to the main driving pathways. Because most CRCs have polyps as progenitor lesions, studying the pathways driving to adenomagenesis is no less important.
Our purpose was the evaluation of microsatellite stability status within conventional colon adenomas and also β-catenin, BRAFV600E and p53 contribution.
The cohort included 101 cases of typical colon adenomas with high grade epithelial dysplasia according to WHO. An immunohistochemistry method was used for the depiction of the expression of targeted proteins, as also their heterogeneity.
Generally, we noted a 10% frequency of MSI events where MSI-H reached a 5% share occurred within the left colon and rectal polyps. β-catenin nuclear overexpression was noted with a 70% frequency and p53 with close to a 24% frequency. In addition, we found a presence of micro-serration foci more often within tubular adenomas, where focal MSI took place more often. Our results indicate that MSI events occur more often than had been theorized earlier. It results in tumour heterogeneity, more complex underlying pathways and finally ontogenetic molecular-diversity of tumours besides similar occurring histopathological features.
结直肠癌属于最常见的恶性肿瘤。预测临床结果并合理选择新辅助化疗需要对主要驱动途径有个性化的了解。由于大多数结直肠癌都有息肉作为祖病变，因此研究驱动腺瘤发生的途径同样重要。
我们的目的是评估传统结肠腺瘤内的微卫星稳定性状态以及β-连环蛋白、BRAFV600E和p53的作用。
该队列包括101例根据世界卫生组织标准诊断为高级别上皮发育异常的典型结肠腺瘤病例。采用免疫组织化学方法描述靶向蛋白的表达及其异质性。
总体而言，我们注意到微卫星不稳定（MSI）事件的发生率为10%，其中MSI-H在左半结肠和直肠息肉中的占比达到5%。β-连环蛋白核过表达的频率为70%，p53的频率接近24%。此外，我们发现微锯齿状病灶更常见于管状腺瘤中，且局灶性MSI也更常发生于此。我们的结果表明，MSI事件的发生频率比早期理论推测的更高。这导致了肿瘤异质性、更复杂的潜在途径，最终除了出现相似的组织病理学特征外，还导致了肿瘤的个体发生分子多样性。
