Department of Pathology, NYU Langone Health, New York, NY.
Int J Gynecol Pathol. 2023 Nov 1;42(6):602-612. doi: 10.1097/PGP.0000000000000936. Epub 2023 Jan 10.
Tumor budding, largely considered a manifestation of epithelial-mesenchymal transition (EMT) is an established prognostic marker for several cancers. In a recent study, tumor budding was associated with poor clinical outcomes in early-stage ovarian clear cell carcinoma. Here, we evaluated the immune expression of 3 proteins shown to be associated with EMT (E-cadherin, β-catenin, and glypican-3) in 72 primary tumors of ovarian clear cell carcinoma with median follow-up of 39.47 mo. E-cadherin and β-catenin expression was further evaluated in tumor buds in 29 (40%) cases. In the tumor mass, diffuse membranous expression of E-cadherin and β-catenin was seen in 83% (60/72) and 81% (58/72) cases, respectively. Nuclear accumulation of E-cadherin was seen in 7 (10%) cases, while none of the cases showed nuclear β-catenin expression. Glypican-3 expression was diffuse in 33.3% (24/72), patchy in 29.2% (21/72), and absent in 37.5% (27/72) cases. Evaluation of tumor buds showed aberrant patterns of expression (complete loss/cytoplasmic accumulation/diminished, discontinuous incomplete membranous staining) of E-cadherin in 29/29 (100%) and of β-catenin in 26/29 (90%) cases. E-cadherin, β-catenin, and glypican-3 expression in the main tumor mass had no association with stage, lymph node status, recurrent/progressive disease, status at last follow-up, survival and histopathologic features ( P >0.05). Our finding of aberrant expression of both E-cadherin and β-catenin in tumor buds indicates involvement of Wnt signaling pathway/EMT in tumor budding and outlines its significance as a prognostic marker especially for early-stage ovarian clear cell carcinoma.
肿瘤芽殖,在很大程度上被认为是上皮-间充质转化(EMT)的表现,是几种癌症的既定预后标志物。在最近的一项研究中,肿瘤芽殖与早期卵巢透明细胞癌的不良临床结局相关。在这里,我们评估了 3 种与 EMT 相关的蛋白(E-钙黏蛋白、β-连环蛋白和糖蛋白 3)在 72 例卵巢透明细胞癌原发肿瘤中的免疫表达,中位随访时间为 39.47 个月。在 29 例(40%)病例中进一步评估了肿瘤芽中的 E-钙黏蛋白和 β-连环蛋白表达。在肿瘤块中,E-钙黏蛋白和 β-连环蛋白的弥漫性膜表达分别见于 83%(60/72)和 81%(58/72)的病例。核内 E-钙黏蛋白聚集见于 7 例(10%)病例,而无核 β-连环蛋白表达。糖蛋白 3 的表达弥漫见于 33.3%(24/72)、斑片状见于 29.2%(21/72)、缺失见于 37.5%(27/72)的病例。对肿瘤芽的评估显示,E-钙黏蛋白在 29/29(100%)和 β-连环蛋白在 26/29(90%)的病例中存在异常表达模式(完全缺失/细胞质积累/减少,不连续不完全的膜染色)。主肿瘤块中 E-钙黏蛋白、β-连环蛋白和糖蛋白 3 的表达与分期、淋巴结状态、复发/进展性疾病、最后随访时的状态、生存和组织病理学特征无关(P>0.05)。我们发现肿瘤芽中 E-钙黏蛋白和 β-连环蛋白的异常表达表明 Wnt 信号通路/EMT 参与了肿瘤芽殖,并强调了其作为特别是早期卵巢透明细胞癌预后标志物的意义。
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