Singh Vivekanand, Manalang Michelle, Singh Meenal, Apte Udayan
Department of Pathology and Laboratory Medicine.
Section of Hematology and Oncology, Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO.
Appl Immunohistochem Mol Morphol. 2018 Oct;26(9):654-657. doi: 10.1097/PAI.0000000000000492.
Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although survival of patients has improved significantly over the last 2 decades, a significant number of patients do not respond to standard chemotherapy. We conducted a pilot study to understand if there was immunophenotypic difference between tumors that respond well to chemotherapy versus that do not. We selected 10 cases of HB from children presenting at our hospital. All patients had initial tissue diagnosis, underwent chemotherapy followed by surgical resection. The cases were divided into 2 groups: aggressive group with 5 cases (all of which had a poor response to chemotherapy); and a good clinical outcome group with 5 cases (all of which responded well to chemotherapy). We excluded the small cell variant of HB from the study because its poor clinical outcome is well known. To be placed in the aggressive group we used the following criteria: <70% necrosis following chemotherapy or recurrence/distant metastasis following chemotherapy. From tissue obtained before chemotherapy, 1 representative block of formalin-fixed, paraffin-embedded tissue was selected for immunohistochemistry. Following review of published literature, antibodies were selected to detect Survivin, PLK-1, Cytokeratin19 (CK19), N-Myc, Yap, Notch2, Hes1, Hes5, and C-Myc. Our results show that Survivin, CK19, and Yap have a diffuse (>75%) positive staining of tumor cells in the aggressive tumors compared with good outcome tumors. However, staining for Yap was weak. Interestingly, there was loss of nuclear expression of C-Myc in majority of tumor cells in aggressive tumors, whereas nuclear staining was retained in most tumor cells of good responders. The N-Myc and PLK-1 immunostains did not reveal any significant differences in the 2 groups of HB. The immunostains for Notch2, Hes1, and Hes5 showed weak to moderately strong staining in tumor cells, but there was no obvious difference in the 2 groups. Our pilot study suggests that in nonsmall cell HB, diffusely increased expression of Survivin and CK19, and loss of nuclear expression of C-Myc marks the tumors as having an aggressive course.
肝母细胞瘤（HB）是儿童最常见的肝脏恶性肿瘤。尽管在过去20年里患者的生存率有了显著提高，但仍有相当数量的患者对标准化疗无反应。我们开展了一项初步研究，以了解对化疗反应良好的肿瘤与无反应的肿瘤之间是否存在免疫表型差异。我们从我院就诊的儿童中选取了10例HB病例。所有患者均有初始组织诊断，接受化疗后进行手术切除。病例分为两组：侵袭性组5例（所有病例对化疗反应均较差）；良好临床结局组5例（所有病例对化疗反应良好）。我们将HB的小细胞变体排除在研究之外，因为其临床结局较差是众所周知的。符合以下标准的病例被归入侵袭性组：化疗后坏死<70%或化疗后复发/远处转移。从化疗前获取的组织中，选取1块福尔马林固定、石蜡包埋的代表性组织块进行免疫组织化学检测。在查阅已发表的文献后，选择抗体来检测生存素、PLK-1、细胞角蛋白19（CK19）、N-Myc、Yap、Notch2、Hes1、Hes5和C-Myc。我们的结果显示，与结局良好的肿瘤相比，侵袭性肿瘤中的生存素、CK19和Yap在肿瘤细胞中呈弥漫性（>75%）阳性染色。然而，Yap的染色较弱。有趣的是，侵袭性肿瘤中大多数肿瘤细胞的C-Myc核表达缺失，而反应良好的肿瘤中大多数肿瘤细胞保留核染色。N-Myc和PLK-1免疫染色在两组HB中未显示出任何显著差异。Notch2、Hes1和Hes5的免疫染色在肿瘤细胞中显示为弱阳性至中等强度染色，但两组之间无明显差异。我们的初步研究表明，在非小细胞HB中，生存素和CK19的弥漫性表达增加以及C-Myc核表达缺失标志着肿瘤具有侵袭性病程。
