Department of Obstetrics and Gynecology, Division of Gynecological Oncology, Winnipeg Health Sciences Center, University of Manitoba, Winnipeg, MB, Canada.
Mod Pathol. 2013 Sep;26(9):1255-63. doi: 10.1038/modpathol.2013.55. Epub 2013 Apr 5.
Low-grade serous carcinomas and serous borderline tumors, combined herein and referred to as low-grade serous tumors, show distinct molecular alterations and clinical behaviors compared with high-grade serous carcinomas. The discrimination between low-grade serous tumors and high-grade serous carcinomas can be challenging on small tissue samples, such as cell blocks of paracentesis fluid or biopsies from omental disease. The purpose of this study was to test the ability of TP53 and CDKN2A immunohistochemistry to distinguish between high-grade serous carcinomas and low-grade serous tumors on small tissue samples. Tissue microarrays containing 582 high-grade serous carcinomas, 45 low-grade serous carcinomas, and 49 serous borderline tumors, confirmed by contemporary histopathological review, were stained for TP53 and CDKN2A (DO7 and E6H4 antibody clones, respectively). TP53 was scored as completely absent, wild-type pattern or overexpressed (>60%), and CDKN2A was scored as either negative/patchy (<90%) or block expression (>90%). The combination of the two markers, ie, the TP53 wild-type pattern and CDKN2A patchy expression, had sensitivity for low-grade serous tumors of 89%, a specificity of 93%, a positive predictive value of 68%, and a negative predictive value of 98%. These markers can, therefore, be used on small biopsies/cell blocks to refute a diagnosis of low-grade serous tumors. These findings may inform emerging neoadjuvant therapeutic strategies in advanced ovarian cancers and may be crucial for future clinical trials on molecular-based therapies.
低级别浆液性癌和浆液性交界性肿瘤（以下简称低级别浆液性肿瘤）与高级别浆液性癌相比，具有明显不同的分子改变和临床行为。在小组织样本（如腹腔穿刺液的细胞块或网膜疾病的活检）上区分低级别浆液性肿瘤和高级别浆液性癌可能具有挑战性。本研究旨在测试 TP53 和 CDKN2A 免疫组化在小组织样本上区分高级别浆液性癌和低级别浆液性肿瘤的能力。组织微阵列包含 582 例高级别浆液性癌、45 例低级别浆液性癌和 49 例浆液性交界性肿瘤，这些肿瘤经当代组织病理学复查证实，并对 TP53 和 CDKN2A（分别为 DO7 和 E6H4 抗体克隆）进行了染色。TP53 评分完全缺失、野生型模式或过表达（>60%），CDKN2A 评分阴性/斑驳（<90%）或块状表达（>90%）。两种标志物的组合，即 TP53 野生型模式和 CDKN2A 斑驳表达，对低级别浆液性肿瘤的敏感性为 89%，特异性为 93%，阳性预测值为 68%，阴性预测值为 98%。因此，这些标志物可用于小活检/细胞块以排除低级别浆液性肿瘤的诊断。这些发现可能为晚期卵巢癌新兴的新辅助治疗策略提供信息，并且对于未来基于分子的治疗临床试验可能至关重要。
