Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL 33612, USA.
Mod Pathol. 2012 Apr;25(4):556-66. doi: 10.1038/modpathol.2011.194. Epub 2011 Dec 16.
Oncotype DX is an RT-PCR-based 21-gene assay validated to provide prognostic and predictive information in the form of a Recurrence Score in patients with estrogen receptor-positive, lymph node-negative breast cancer. Although the Recurrence Score was shown to correlate with several histopathological tumor features, there is a significant proportion of cases showing an apparent discrepancy between Recurrence Score and risk estimates based on the traditional clinicopathological tumor features. In this study, we tested whether a proliferating, cellular stroma and/or admixed inflammatory cells may result in an artificially increased Recurrence Score in low-grade invasive breast cancers. We analyzed the histopathological features in 141 low-grade invasive breast carcinomas, including 41 special type (tubular, cribriform and mucinous) carcinomas, with available Recurrence Score. The tumor stroma was evaluated for increased cellularity and presence of inflammatory cells. Double immunohistochemical stains for pancytokeratin and Ki-67 was performed to assess the cell proliferation in tumor vs stromal/inflammatory cells. The clinicopathological features of tumors with Recurrence Score <18 (low risk) were compared with those with Recurrence Score ≥18 (intermediate/high risk). Carcinomas associated with Recurrence Score ≥18 showed lower progesterone receptor immunoreactivity, increased stromal cellularity and presence of inflammatory cells associated with the tumor. Double immunohistochemical stains showed significantly increased proliferation in stromal/inflammatory cells compared with carcinoma cells in cases associated with Recurrence Score ≥18. A Ki-67-positive stromal/tumor cells ratio of >1 predicted Recurrence Score ≥18 with an area under the curve of 0.8967 on receiver operator curve analysis (P<0.0001). Our results suggest that the presence of increased stromal cellularity and/or associated inflammatory cells in low-grade invasive breast carcinomas may contribute to an apparently increased risk of recurrence according to Oncotype DX Recurrence Score. Careful assessment and correlation with histopathological features in such cases may help in determining the appropriate patient management.
Oncotype DX 是一种基于 RT-PCR 的 21 基因检测方法，可提供雌激素受体阳性、淋巴结阴性乳腺癌患者的预后和预测信息，表现为复发评分。尽管复发评分与几种组织病理学肿瘤特征相关，但仍有相当一部分病例显示出复发评分与基于传统临床病理肿瘤特征的风险评估之间存在明显差异。在这项研究中，我们检测了增生性细胞基质和/或混合炎症细胞是否会导致低级别浸润性乳腺癌中复发评分的人为升高。我们分析了 141 例低级别浸润性乳腺癌的组织病理学特征，包括 41 例特殊类型（管状、筛状和黏液性）癌，这些癌都有可用的复发评分。评估肿瘤基质的细胞丰富度和炎症细胞的存在。进行细胞角蛋白和 Ki-67 的双重免疫组织化学染色，以评估肿瘤与基质/炎症细胞中的细胞增殖情况。将复发评分<18（低风险）的肿瘤的临床病理特征与复发评分≥18（中/高风险）的肿瘤进行比较。与复发评分≥18 相关的癌显示孕激素受体免疫反应性降低，基质细胞丰富度增加，与肿瘤相关的炎症细胞存在。双重免疫组织化学染色显示，与复发评分≥18 相关的病例中，基质/炎症细胞的增殖明显高于癌细胞。Ki-67 阳性的基质/肿瘤细胞比值>1 预测复发评分≥18，ROC 分析曲线下面积为 0.8967（P<0.0001）。我们的结果表明，低级别浸润性乳腺癌中基质细胞丰富度增加和/或相关炎症细胞的存在可能导致根据 Oncotype DX 复发评分出现明显的复发风险增加。在这些病例中，仔细评估并与组织病理学特征相关联，可能有助于确定适当的患者管理。
