Discrepancies in Hormone Receptor and HER2 Expression between Malignant Serous Effusions and Paired Tissues from Primary or Recurrent Breast Cancers

Abstract

Objectives: Immunohistochemistry (IHC) for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) biomarkers has prognostic and therapeutic value in breast cancer, while it facilitates molecular subtyping. This study aimed to identify subtype discordance and its clinical significance among different phases of breast cancer evolution, focusing on effusion cytology samples diagnosed with malignancy. Methods: Our electronic archive was searched for all effusion cases diagnosed as breast carcinomas within a pre-defined period (January 2018-October 2021), and their cell blocks (CBs) were subjected to ER, PR, and HER2 IHC or in situ hybridization. Furthermore, information regarding the same biomarkers from previously obtained tissue specimens of these patients was extracted. Results: Only 2/76 (2.6%) of the breast cancer patients analyzed showed a malignant effusion at their initial presentation. The triple negative breast cancer (TNBC) phenotype was found significantly more often at effusion CBs, compared to their paired biopsies received during initial diagnosis (30/70 vs 16/70; p<0.001). In addition, the presence of TNBC subtype was significantly associated with an earlier development of a malignant effusion, more specifically at initial diagnosis (P<0.001; log-rank test), at first recurrence/metastasis (either solid or effusion) (P=0.012; log-rank test), at effusion (P=0.007; log-rank test), and at any tumor evolution phase (P=0.009; log-rank test). Conclusion: Serous effusion cytology provides high-quality material for ancillary techniques, especially when CBs are prepared, reflecting cancer heterogeneity.

Comparing the HER2 Status of the Primary Tumor to That of Disseminated Tumor Cells in Early Breast Cancer

“…Mouse monoclonal antibodies A45-B/B3 directed against pancytokeratin (Micromet, Munich, Germany) and keratin 8/18 Ab-1 (Thermo Fisher Scientific, Fremont, CA, USA) and mouse monoclonal antibody directed against c-erbB-2 (Her-2/neu) (BioGenex, Fremont, CA, USA) were used. For cytokeratin staining, two slides with 1.5 × 10 6 cells per patient were evaluated, according to the consensus recommendations for standardized tumor cell detection [ 13 ]. DTC positivity was defined as at least one pancytokeratin-positive cell with typical cell morphology [ 45 ] per 1.5 × 10 6 cells.…”

“…Previous studies showed that molecular characteristics can vary between the primary tumor (PT) and distant metastases [ 12 , 13 , 14 ]. More specifically, discrepancies in HER2 expression between the PT and metastases could be shown in almost 50% of cases [ 15 , 16 ].…”