A multicentre validation of Metasin: a molecular assay for the intraoperative assessment of sentinel lymph nodes from breast cancer patients

Abstract

Aims: Treatment strategies for breast cancer continue to evolve. No uniformity exists in the UK for the management of node-positive breast cancer patients. Most centres continue to use conventional histopathology of sampled sentinel lymph nodes (SLNs), which requires delayed axillary clearance in up to 25% of patients. Some use touch imprint cytology or frozen section for intraoperative testing, although both have inherent sensitivity issues. An intraoperative molecular diagnostic approach helps to overcome some of these limitations. The aim of this study was to assess the clinical effectiveness of Metasin, a molecular method for the intraoperative evaluation of SLNs. Methods and results: RNA from 3296 lymph nodes from 1836 patients undergoing SLN assessment was analysed with Metasin. Alternate slices of tissue were examined in parallel by histology. Cases deemed to be discordant were analysed by protein gel electrophoresis. There was concordance between Metasin and histology in 94.1% of cases, with a sensitivity of 92% [95% confidence interval (CI) 88-94%] and a specificity of 97% (95% CI 2016 , 68, 875-887. DOI: 10.1111 95-97%). Positive and negative predictive values were 88% and 98%, respectively. Over half of the discordant cases (4.4%) were ascribed to tissue allocation bias (TAB).Conclusions: Clinical validation of the Metasin assay suggests that it is sufficiently sensitive and specific to make it fit for purpose in the intraoperative setting.

Evaluation of the Metasin assay for intraoperative assessment of sentinel lymph node metastases in breast cancer

“…Six patients (2.4%) were singularly positive for MGB compared with 1.63% in a previous study 21. These patients are significant because their metastases would not be detected by the OSNA system which only detects CK19.…”

“…Metasin is reliable with a failure rate of just 0.8%, comparing favourably with our routine qRT-PCR techniques (4.9%), a further study of Metasin (1.5%)21 and the OSNA system (1.4%) 22. The reproducibility of Metasin for CK19, MGB and PBGD is excellent for a RT-qPCR assay, where variation in Cq values should generally be <1.5 23…”

“…After adjustment for TAB, the figures are 92.2% and 91.4%, respectively. Two previous Metasin studies, after adjustment for TAB, have reported the sensitivity of Metasin compared with histology as 92%–95% and the specificity as 97% 11 21…”

“…The concordance improved to 96.5% after examination of deeper sections, immunostaining with MNF116, a pancytokeratin marker and using Genesearch 11. A multicentre study reported a 95.6% concordance with histology, based on a case analysis and examination of deeper sections and immunostaining with MNF116 21. Snook et al 22 gave the overall concordance between OSNA and histology as 96%.…”

Clinical significance of MSKCC nomogram on guiding the application of touch imprint cytology and frozen section in intraoperative assessment of breast sentinel lymph nodes

“…Over the past decade, many researchers are keen to apply molecular assays to improve intra-operative pathologic accuracy of breast SLNs, such as the Metasin assay [ 18 , 19 ] and one-step nucleic acid amplification assay (OSNA) [ 20 , 21 ], but neglect to give full consideration to the existing mature pathologic techniques (TIC and FS), which are widely used in clinical practice. In addition, a study of OSNA in 552 patients showed both OSNA and TIC can serve as qualified intra-operative assessments of SLNs, and suggested that OSNA can be applied as a complement to histopathologic assessment, but cannot replace pathology with serial sectioning [ 22 ].…”