Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Pathology and Cytology, Karolinska University Laboratory, Stockholm, Sweden.
J Clin Pathol. 2018 Sep;71(9):787-794. doi: 10.1136/jclinpath-2017-204976. Epub 2018 Mar 27.
The accuracy of biomarker assessment in breast pathology is vital for therapy decisions. The therapy predictive and prognostic biomarkers oestrogen receptor (ER), progesterone receptor, HER2 and Ki67 may act as surrogates to gene expression profiling of breast cancer. The aims of this study were to investigate the concordance of consecutive biomarker assessment by immunocytochemistry on preoperative fine-needle aspiration cytology versus immunohistochemistry (IHC) on the corresponding resected breast tumours. Further, to investigate the concordance with molecular subtype and correlation to stage and outcome.
Two retrospective cohorts comprising 385 breast tumours with clinicopathological data including gene expression-based subtype and up to 10-year overall survival data were evaluated.
In both cohorts, we identified a substantial variation in Ki67 index between cytology and histology and a switch between low and high proliferation within the same tumour in 121/360 cases. ER evaluations were discordant in only 1.5% of the tumours. From cohort 2, gene expression data with PAM50 subtype were used to correlate surrogate subtypes. IHC-based surrogate classification could identify the correct molecular subtype in 60% and 64% of patients by cytology (n=63) and surgical resections (n=73), respectively. Furthermore, high Ki67 in surgical resections but not in cytology was associated with poor overall survival and higher probability for axillary lymph node metastasis.
This study shows considerable differences in the prognostic value of Ki67 but not ER in breast cancer depending on the diagnostic method. Furthermore, our findings show that both methods are insufficient in predicting true molecular subtypes.
生物标志物在乳腺病理学中的评估准确性对于治疗决策至关重要。治疗预测和预后生物标志物雌激素受体（ER）、孕激素受体、HER2 和 Ki67 可以作为乳腺癌基因表达谱分析的替代物。本研究旨在探讨免疫细胞化学检测术前细针穿刺细胞学与相应切除乳腺肿瘤免疫组化（IHC）连续评估生物标志物的一致性。此外，还探讨了与分子亚型的一致性以及与分期和结局的相关性。
评估了两个包含临床病理数据的回顾性队列，包括基于基因表达的亚型和最多 10 年的总生存数据，这些数据来自 385 例乳腺肿瘤。
在两个队列中，我们发现细胞学和组织学之间 Ki67 指数存在很大差异，在 121/360 例肿瘤中同一肿瘤内的增殖率在低水平和高水平之间发生了转换。仅在 1.5%的肿瘤中 ER 评估存在不一致。从队列 2 中，使用 PAM50 亚型的基因表达数据来关联替代亚型。基于 IHC 的替代分类可以在 60%和 64%的细胞学（n=63）和手术切除（n=73）患者中正确识别分子亚型。此外，手术切除中 Ki67 高而非细胞学中 Ki67 高与总生存不良和腋窝淋巴结转移的可能性更高相关。
本研究表明，Ki67 而不是 ER 在乳腺癌中的预后价值取决于诊断方法，存在相当大的差异。此外，我们的发现表明，这两种方法都不足以预测真正的分子亚型。
