title: A cut-off of 2150 cytokeratin 19 mRNA copy number in sentinel lymph node may be a powerful predictor of non-sentinel lymph node status in breast cancer patients.
abstract: Since 2007, one-step nucleic acid amplification (OSNA) has been used as a diagnostic system for sentinel lymph node (SLN) examination in patients with breast cancer. This study aimed to define a new clinical cut-off of CK19 mRNA copy number based on the calculation of the risk that an axillary lymph node dissection (ALND) will be positive. We analyzed 1529 SLNs from 1140 patients with the OSNA assay and 318 patients with positive SLNs for micrometastasis (250 copies) and macrometastasis (5000 copies) underwent ALND. Axillary non-SLNs were routinely examined. ROC curves and Youden's index were performed in order to identify a new cut-off value. Logistic regression models were performed in order to compare OSNA categorical variables created on the basis of our and traditional cut-off to better identify patients who really need an axillary dissection. 69% and 31% of OSNA positive patients had a negative and positive ALND, respectively. ROC analysis identified a cut-off of 2150 CK19 mRNA copies with 95% sensitivity and 51% specificity. Positive and negative predictive values of this new cut-off were 47% and 96%, respectively. Logistic regression models indicated that the cut-off of 2150 copies better discriminates patients with node negative or positive in comparison with the conventional OSNA cut-off (p<0.0001). This cut-off identifies false positive and false negative cases and true-positive and true negative cases very efficiently, and therefore better identifies which patients really need an ALND and which patients can avoid one. This is why we suggest that the negative cut-off should be raised from 250 to 2150. Furthermore, we propose that for patients with a copy number that ranges between 2150 and 5000, there should be a multidisciplinary discussion concerning the clinical and bio-morphological features of primary breast cancer before any decision is taken on whether to perform an ALND or not.
authors.affiliation: Biostatistics Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Terrenato
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: D'Alicandro
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Casini
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Perracchio
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rollo
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Salvo
authors.affiliation: Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Di Filippo
authors.affiliation: Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Di Filippo
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Pescarmona
authors.affiliation: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy.|Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maugeri-Saccà
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Simonetta
authors.identifier: http://orcid.org/0000-0001-7913-7023
authors.initials: S
authors.lastname: Buglioni
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism / Q000592:standards; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000235:genetics* / Q000378:metabolism / Q000592:standards; D008207:Lymphatic Metastasis; D025202:Molecular Diagnostic Techniques / Q000592:standards; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism / Q000592:standards; D000071036:Sentinel Lymph Node / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D053539:Keratin-19; D012333:RNA, Messenger