Journal Article

Disseminated tumour cells in the bone marrow in early breast cancer: morphological categories of immunocytochemically positive cells have different impact on clinical outcome

Renolen, A., Schirmer, C. B., Naume, B., Synnestvedt, M., Schlichting, E., Nesland, J. M., Borgen, E., Giercksky, K. E.

2013

Overview

Detection of disseminated tumour cells (DTCs) in bone marrow by immunocytochemistry (ICC) includes morphological evaluation of cytokeratin immunopositive cells. The aim of this study was to disclose the prognostic significance of different morphological categories of ICC-positive cells according to treatment status and tumour subtype. Bone marrow samples (at surgery) were analysed for the presence of cytokeratin-positive DTCs by a standard immunocytochemical method. The immunopositive cells were classified into the following categories, prior to any analysis of the association between DTCs and clinical outcome: tumour cells (TC), uninterpretable cells (UIC), hematopoietic cells (HC), and questionable HC (QHC). The analysis included 747 early breast cancer patients. Median follow-up was 84 months for relapse, and 99 months for death. The categorisation of the ICC positive cells revealed TC in 13.3 % of the patients, whereas 13.1, 17.8, and 21.4 % of the cases were positive for UIC, QHC, and HC, respectively. Analysing all patients, only TC and UIC predicted systemic relapse. Separate analysis of all patients not receiving adjuvant systemic treatment (No-Adj; n  = 389) showed that only QHC were associated with reduced survival (DDFS: p  = 0.008; BCSS: p  = 0.004, log rank) and the presence of QHC also remained significant in multivariate analysis. Primary tumour subgroup analysis (of all patients) by hormone receptors (HR) and HER2, demonstrated that only TC/UIC had prognostic impact in the HR+/HER2− patients, whereas presence of QHC was associated with unfavourable outcome only in triple negative patients (DDFS: p  = 0.004; BCSS: p  = 0.024). Patients with ≥3HC had improved outcome compared to those with fewer/no HC (DDFS: p  = 0.005; BCSS: p  = 0.009). Hence, morphological DTC subgroups may differ in clinical significance according to primary tumour subtype and treatment status. This emphasises the importance of DTC characterisation, and separate analyses of DTC categories according to tumour subtype. Hematopoietic (“false positive”) cells might predict an immune-related favorable clinical outcome.

• Publisher: Springer US,Springer,Springer Nature B.V
• Subject: Biological and medical sciences / Bone marrow / Bone Marrow - pathology / Breast cancer / Breast Neoplasms - metabolism / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Breast Neoplasms - therapy / Cancer research / Cancer therapies / Carcinoma, Ductal, Breast - metabolism / Carcinoma, Ductal, Breast - mortality / Carcinoma, Ductal, Breast - secondary / Carcinoma, Ductal, Breast - therapy / Carcinoma, Lobular - metabolism / Carcinoma, Lobular - mortality / Carcinoma, Lobular - secondary / Carcinoma, Lobular - therapy / Cell Shape / Cellular biology / Clinical outcomes / Clinical Trial / Cross-Sectional Studies / Cytochemistry / False Positive Reactions / Female / Gynecology. Andrology. Obstetrics / Humans / Immunohistochemistry / Impact analysis / Kaplan-Meier Estimate / Keratin / Lymphatic Metastasis / Mammary gland diseases / Mastectomy, Segmental / Medical sciences / Medicine / Medicine & Public Health / Middle Aged / Morphology / Multiple tumors. Solid tumors. Tumors in childhood (general aspects) / Multivariate Analysis / Oncology / Patient outcomes / Prognosis / Proportional Hazards Models / Receptor, ErbB-2 - metabolism / Receptors, Estrogen - metabolism / Receptors, Progesterone - metabolism / Treatment Outcome / Tumors