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.
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 (P < 10E-6). Moreover, ALND status positivity was significantly associated to Ct value of MG (z = 2.4; P = 0.018) and CK19 (z = 3.2; P = 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.
Department of Surgery, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium.
I
I
Veys
S
S
Majjaj
R
R
Salgado
D
D
Noterman
J C
JC
Schobbens
F
F
Manouach
P
P
Bourgeois
J M
JM
Nogaret
D
D
Larsimont
V
V
Durbecq
D001530:Belgium; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007430:Intraoperative Care; D053539:Keratin-19 / Q000235:genetics*; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D015412:Mastectomy, Segmental; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D012086:Reoperation; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy; D016896:Treatment Outcome; D014598:Uteroglobin / Q000235:genetics*
D053539:Keratin-19; D014598:Uteroglobin