Abstract

Background: Colorectal carcinomas (CRCs) are uncommon tumors in children. Here, we elucidate three cases of childhood CRCs with their underlying molecular derangements using immunohistochemistry (IHC) with emphasis on BRAF mutation. Case summary: All three CRCs were sporadic tumors involving the left colon with two of them having a mucinous phenotype. We performed IHC for BRAF, p53 and β-catenin along with markers of microsatellite instability (MSI) in all three tumors. All the tumors had diffuse strong cytoplasmic BRAF positivity, with focal p53 positivity in two cases and cytoplasmic β-catenin staining in one case. One case showed CpG island hypermethylation with isolated loss of PMS2 staining. None of the cases had any family history of CRC. Conclusions: IHC can be used as a surrogate marker for determining the underlying molecular derangements in CRC. Sporadic CRCs in children are a cumulative effect of multiple mutations, of which BRAF mutation is significant and critical for planning targeted therapy.

摘要

背景：结直肠癌（CRCs）是儿童中少见的肿瘤。在这里，我们使用免疫组织化学 (IHC) 阐明了三例儿童 CRC 及其潜在的分子紊乱，重点是 BRAF 突变。病例总结：所有三个结直肠癌都是累及左结肠的散发性肿瘤，其中两个具有粘液表型。我们对所有三种肿瘤中的 BRAF、p53 和 β-连环蛋白以及微卫星不稳定性 (MSI) 标志物进行了 IHC。所有肿瘤均呈弥漫性强细胞质BRAF阳性，2例局灶性p53阳性，1例细胞质β-连环蛋白染色。1 例显示 CpG 岛高甲基化，PMS2 染色分离缺失。所有病例均无CRC家族史。结论：IHC 可用作确定 CRC 中潜在分子紊乱的替代标记。儿童散发性 CRC 是多种突变的累积效应，其中 BRAF 突变对于规划靶向治疗具有重要意义和关键性。