Buyucek Seyma, Coskun Sinem Kantarcioglu, Onal Binnur, Gamsizkan Mehmet, Cangur Sengul, Esbah Onur
Department of Pathology and Cytology, School of Medicine, Duzce University, Konuralp Campus, Duzce, Turkey.
Department of Statistics, School of Medicine, Duzce University, Konuralp Campus, Duzce, Turkey.
J Environ Pathol Toxicol Oncol. 2023;42(1):65-77. doi: 10.1615/JEnvironPatholToxicolOncol.2022044380.
Receptor tyrosine kinase pathway is frequently searched for cancer causing mutations in tumors. Emerging targeted therapies are gleam of hope for them. Infiltrating urothelial carcinoma can have many morphological aspects according to their differentiation/variants. To evaluate KRAS, BRAF, and PIK3CA mutations and HER2, EGFR, and p16 expression, we divided urothelial carcinomas into two groups: differentiated/variants (n = 12) and conventional (n = 12). We compared results with clinical, demographic, histopathologic features and survival rates. No statistically significant results could be obtained in the comparison of histopathologic properties/survival rates with mutation analysis and EGFR, HER2, and p16 status. Differentiated/variants urothelial carcinoma showed higher EGFR expression (P < 0.001). Glandular differentiation was the most frequent type, followed by squamous and sarcomatoid differentiation. We observed the most common mutation at KRAS with a propensity for urothelial carcinoma with glandular differentiation. More than one mutation/high protein expression was seen in some tumors. Targeted therapies for KRAS mutation can be effective at urothelial carcinoma with glandular differentiation. Heterologous expression of relevant proteins and genes can be a cause for targeted treatment obstacle. The determination of the molecular characters of tumors is a guide in creating targeted treatment algorithms and in choosing the patient.
受体酪氨酸激酶通路经常被用于寻找肿瘤中导致癌症的突变。新兴的靶向治疗方法为患者带来了一线希望。浸润性尿路上皮癌根据其分化程度/变体可能具有多种形态学特征。为了评估KRAS、BRAF和PIK3CA突变以及HER2、EGFR和p16的表达情况，我们将尿路上皮癌分为两组：分化型/变体（n = 12）和传统型（n = 12）。我们将结果与临床、人口统计学、组织病理学特征及生存率进行了比较。在组织病理学特征/生存率与突变分析以及EGFR、HER2和p16状态的比较中，未获得具有统计学意义的结果。分化型/变体尿路上皮癌显示出更高的EGFR表达（P < 0.001）。腺性分化是最常见的类型，其次是鳞状和肉瘤样分化。我们观察到KRAS突变最为常见，且倾向于发生在腺性分化的尿路上皮癌中。在一些肿瘤中发现了不止一种突变/高蛋白表达。针对KRAS突变的靶向治疗可能对腺性分化的尿路上皮癌有效。相关蛋白质和基因的异源表达可能是靶向治疗的障碍。确定肿瘤的分子特征可为制定靶向治疗算法和选择患者提供指导。
