Evaluation of the histological size of the sentinel lymph node metastases using RT–PCR assay: a rapid tool to estimate the risk of non-sentinel lymph node invasion in patients with breast cancer

I. Veys (1) , S. Majjaj (2) , R. Salgado (2) , D. Noterman (1) , J. C. Schobbens (1) , F. Manouach (2) , P. Bourgeois (3) , J. M. Nogaret (1) , D. Larsimont (2) , V. Durbecq (2)

1 Institut Jules Bordet [Bruxelles]
2 Service d'anatomie pathologique [Bruxelles]
3 Department of Nuclear Medicine, Jules Bordet Institute

A RT–PCR assay (GeneSearch™, Veridex, LLC), FDA approved and CE marked to detect metastases >0.2 mm in sentinel lymph nodes (SLNs) is used intra-operatively for the management of patients with breast cancer. The assay provides qualitative results by applying cut-off values to cycle times (Ct) for mammaglobin (MG) and cytokeratin-19 (CK19) genes. Aims of this study were to evaluate the performance of the quantitative Ct values to estimate the size of nodal metastases and the risk of additional disease in non-SLNs. SLNs from 367 patients were clinically processed using both BLN assay and post-operative histology. Complementary axillary lymph node dissection (ALND) was performed concurrently in case of BLN assay positivity or tumour size >2 cm. BLN positivity was reported in 19.6% of the patients for a sensitivity of 89%. BLN specificity (94.5%) and negative predictive value (97.5%) clearly demonstrated its reliability to guide ALND decision. All, except one, residual axillary metastases were found in BLN-positive patients. Considering the 78 patients with SLN positivity or discordant status according to both criteria, the metastases histological size was significantly correlated to the expression level of MG (ρ = 0.62) and CK19 (ρ = 0.64) genes ( < 10E-6). Moreover, ALND status positivity was significantly associated to Ct value of MG ( = 2.4;  = 0.018) and CK19 ( = 3.2;  = 0.001). The high intra-operative quality performance of the BLN assay minimizes the need for second surgeries for ALND. Results from this investigational study suggest that markers Ct value may provide, intra-operatively, valuable metastases size data and a risk prediction of additional disease in non-SLNs.

Mots clés: Breast cancer; Sentinel lymph node; Molecular assay; Nodal metastases size

I. Veys, S. Majjaj, R. Salgado, D. Noterman, J. C. Schobbens, et al.. Evaluation of the histological size of the sentinel lymph node metastases using RT–PCR assay: a rapid tool to estimate the risk of non-sentinel lymph node invasion in patients with breast cancer. Breast Cancer Research and Treatment, 2009, 124 (3), pp.599-605. ⟨10.1007/s10549-009-0555-2⟩. ⟨hal-00533600⟩