Loh Seow Foong, Cooper Caroline, Selinger Christina I, Barnes Elizabeth H, Chan Charles, Carmalt Hugh, West Richard, Gluch Laurence, Beith Jane M, Caldon C Elizabeth, O'Toole Sandra
Department of Breast Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
J Clin Pathol. 2015 Mar;68(3):187-91. doi: 10.1136/jclinpath-2014-202331. Epub 2014 Dec 12.
The diagnosis of intraductal papillary lesions of the breast on core biopsy remains challenging in pathology, with most patients requiring formal surgical excision for a definitive diagnosis. The aim of this study was to determine whether a representative panel of proliferative cell cycle immunohistochemical markers (cyclin A2, cyclin B1 and cyclin D1) could improve the specificity of pathological diagnosis of these lesions.
A series of 68 surgically excised intraductal papillary lesion cases were retrospectively selected, and immunohistochemistry for cyclin A2, cyclin B1 and cyclin D1 was performed.
Cyclin B1 (OR 1.80, 95% CI 1.01 to 3.2, p=0.046) and cyclin D1 (OR 1.13, 95% CI 1.05 to 1.22, p=0.002) expression was independently associated with a diagnosis of malignancy in papillary lesions, although expression was frequently heterogeneous and only focal. Cyclin A2 expression (OR 0.76, 95% CI 0.41 to 1.4, p=0.38) was not associated with a malignant diagnosis in multivariable logistic regression models. All three cyclins displayed high sensitivity (80%-95%) for a diagnosis of malignancy, although cyclin B1 showed a superior specificity of 72.7% compared with the low specificity of cyclins A2 and D1.
Our study has identified for the first time that the expression of key cell cycle markers differs between benign and malignant papillary breast lesions and identified changes to the mitotic marker, cyclin B1, as particularly significant. However, given the low level and heterogeneous nature of expression of these markers, there remains a significant risk of undersampling in core biopsies and thus they are unlikely to be useful in routine clinical practice.
在病理学中，通过粗针活检诊断乳腺导管内乳头状病变仍具有挑战性，大多数患者需要进行正式的手术切除以明确诊断。本研究的目的是确定一组具有代表性的增殖细胞周期免疫组化标志物（细胞周期蛋白A2、细胞周期蛋白B1和细胞周期蛋白D1）是否能提高这些病变病理诊断的特异性。
回顾性选取68例手术切除的导管内乳头状病变病例，并对细胞周期蛋白A2、细胞周期蛋白B1和细胞周期蛋白D1进行免疫组化检测。
细胞周期蛋白B1（比值比1.80，95%置信区间1.01至3.2，p = 0.046）和细胞周期蛋白D1（比值比1.13，95%置信区间1.05至1.22，p = 0.002）的表达与乳头状病变的恶性诊断独立相关，尽管表达通常是异质性的且仅为局灶性。在多变量逻辑回归模型中，细胞周期蛋白A2表达（比值比0.76，95%置信区间0.41至1.4，p = 0.38）与恶性诊断无关。所有三种细胞周期蛋白对恶性诊断均显示出高敏感性（80% - 95%），尽管细胞周期蛋白B1的特异性为72.7%，优于细胞周期蛋白A2和D1的低特异性。
我们的研究首次发现，良性和恶性乳腺乳头状病变之间关键细胞周期标志物的表达存在差异，并确定有丝分裂标志物细胞周期蛋白B1的变化尤为显著。然而，鉴于这些标志物表达水平低且具有异质性，粗针活检中仍存在显著的取样不足风险，因此它们不太可能在常规临床实践中发挥作用。
