RESUMO
BACKGROUND: Intra-operative assessment is not routinely performed in the UK due to poor sensitivity of available methods and overburdened pathology resources. We conducted a prospective clinical feasibility study of the GeneSearch Breast Lymph Node (BLN) Assay (Veridex, LLC, Warren, NJ) to confirm its potential usefulness within the UK healthcare system. METHODS: In the assay 50% of the lymph node was processed to detect the presence of cytokeratin-19 and mammaglobin mRNA. The assay was calibrated to detect metastases >0.2 mm. Assay results were compared to H&E performed on each face of approximately 2 mm alternating node slabs and 3 additional sections cut at approximately 150 microm interval from each face of the node slab. RESULTS: 124 sentinel lymph nodes were removed from 82 breast cancer patients. The assay correctly identified all 6 patients with sentinel node macrometastases (>2.0 mm), and 2 of 3 patients with sentinel node micrometastases (0.2-2.0 mm). Sentinel lymph nodes in 4 patients were assay positive but histology negative. Two of these four patients had isolated tumor cells seen by histology. The overall concordance with histology was 93.9% (77/82), with sensitivity of 88.9% (8/9, 95% CI 56.5-98%), specificity of 94.6% (69/73, 95% CI 86.7-97.8%), positive predictive value of 66.7% (8/12, 95% CI 39.1-86.2%) and negative predictive value of 98.6% (69/70, 95% CI 92.3-99.7%). The assay was performed in a median time of 32 min (range 26-69 min). CONCLUSION: Intra-operative assessment of sentinel lymph node can be performed rapidly and accurately using the GeneSearch BLN Assay.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bioensaio , Biomarcadores Tumorais/metabolismo , Estudos de Viabilidade , Feminino , Humanos , Período Intraoperatório , Queratina-19/genética , Excisão de Linfonodo , Linfonodos/metabolismo , Metástase Linfática , Mamoglobina A , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela , Taxa de Sobrevida , Uteroglobina/genéticaRESUMO
Sentinel lymph node biopsy (SLNB) is becoming accepted as standard of care for axillary staging in breast cancer. World Health Organization (WHO) re-classification of axillary metastases into macrometastases, micrometastases and individual tumour cells has highlighted the issues of sampling and further histological examination of the initially negative SLNB. Molecular detection of metastatic breast cancer cells in lymph nodes is now available as a commercial kit for intraoperative use and can resolve the sampling issue. Semiquantitative assessment of axillary lymph node tumour burden can now be made using two separate technologies (histology and reverse transcriptase-polymerase chain reaction). The clinical implications of low metastatic axillary lymph node tumour burden are not clear, and future trials need to include molecular data. The consequences of the availability of molecular assessment are reviewed.