Ibrahiem Afaf T, Eladl Entsar, Toraih Eman A, Fawzy Manal S, Abdelwahab Khaled, Elnaghi Khaled, Emarah Ziad, Shaalan Aly A M, Ehab Ziad, Soliman Nahed A
Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Department of Laboratory Medicine and pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Diagnostics (Basel). 2023 Jan 9;13(2):237. doi: 10.3390/diagnostics13020237.
Patients with colorectal cancer in different stages show variable outcomes/therapeutic responses due to their distinct tumoral biomarkers and biological features. In this sense, this study aimed to explore the prognostic utility of BRAF, programmed death-1 (PD1), and its ligand (PDL1) protein signatures in colon adenocarcinoma. The selected protein markers were explored in 64 archived primary colon adenocarcinomas in relation to clinicopathological features. BRAF overexpression was found in 39% of the cases and was significantly associated with grade 3, N1, advanced Dukes stage, presence of relapse, and shorter overall survival (OS). PD1 expression in the infiltrating immune cells (IICs) exhibited significant association with T2/T3, N0/M0, early Dukes stage, and absence of relapse. PDL1 expression in IICs is significantly associated with advanced nodal stage/distant metastasis, advanced Dukes stage, and shorter OS. Meanwhile, PDL1 expression in neoplastic cells (NC) was associated with the advanced lymph node/Dukes stage. A positive combined expression pattern of PDL1 in NC/IICs was associated with poor prognostic indices. Tumor PDL1 expression can be an independent predictor of OS and DFS. The multivariate analyses revealed that short OS was independently associated with the RT side location of the tumor, PD1 expression in stromal IICs, and PDL1 expression in NC. In conclusion, overexpression of BRAF in colon adenocarcinoma is considered a poor prognostic pathological marker. In addition, PDL1 expression in NC is considered an independent prognostic factor for DFS/OS. Combined immunohistochemical assessment for BRAF and PD1/PDL1 protein expressions in colon adenocarcinoma might be beneficial for selecting patients for future targeted therapy.
处于不同阶段的结直肠癌患者由于其独特的肿瘤生物标志物和生物学特征而表现出不同的预后/治疗反应。从这个意义上说，本研究旨在探讨BRAF、程序性死亡受体1（PD1）及其配体（PDL1）蛋白标志物在结肠腺癌中的预后价值。在64例存档的原发性结肠腺癌中，研究了所选蛋白标志物与临床病理特征的关系。在39%的病例中发现BRAF过表达，且与3级、N1、晚期杜克分期、复发的存在以及较短的总生存期（OS）显著相关。浸润性免疫细胞（IICs）中的PD1表达与T2/T3、N0/M0、早期杜克分期以及无复发显著相关。IICs中的PDL1表达与晚期淋巴结分期/远处转移、晚期杜克分期以及较短的OS显著相关。同时，肿瘤细胞（NC）中的PDL1表达与晚期淋巴结/杜克分期相关。NC/IICs中PDL1的阳性联合表达模式与不良预后指标相关。肿瘤PDL1表达可作为OS和无病生存期（DFS）的独立预测指标。多因素分析显示，较短的OS与肿瘤的右半侧位置、基质IICs中的PD1表达以及NC中的PDL1表达独立相关。总之，结肠腺癌中BRAF的过表达被认为是一个不良预后的病理标志物。此外，NC中的PDL1表达被认为是DFS/OS的独立预后因素。对结肠腺癌中BRAF和PD1/PDL1蛋白表达进行联合免疫组化评估可能有助于为未来的靶向治疗选择患者。
