title: Quantitative molecular analysis of sentinel lymph node may be predictive of axillary node status in breast cancer classified by molecular subtypes.
abstract: To determine the performance of intraoperative one-step nucleic acid amplification (OSNA) assay in detecting sentinel lymph node metastases compared to postoperative histology taking into account breast cancer molecular classification and to evaluate whether the level of cytokeratin 19 mRNA copy number may be useful in predicting the likelihood of a positive axillary lymph node dissection. OSNA assay was performed in a prospective series of 903 consecutive sentinel lymph nodes from 709 breast cancer patients using 2 alternate slices of each sentinel lymph node. The remaining 2 slices were investigated by histology. Cytokeratin 19 mRNA copy number, which distinguishes negative cases (<250 copies), micrometastases (+, ≥250≤5000 copies) and macrometastases (++, >5000 copies), was compared to axillary lymph node dissection status and to the biological tumor profile. Concordance between OSNA and histopathology was 95%, specificity 95% and sensitivity 93%. Multiple Corresponce Analysis and logistic regression evidenced that positive axillary lymph node dissection was significantly associated with a higher cytokeratin 19 mRNA copy number (>5000; p<0.0001), HER2 subtype (p = 0.007) and lymphovascular invasion (p<0.0001). Conversely, breast cancer patients with cytokeratin 19 mRNA copy number <2000 mostly presented a luminal subtype and a negative axillary lymph node dissection. We confirmed that OSNA assay can provide standardized and reproducible results and that it represents a fast and quantitative tool for intraoperative evaluation of sentinel lymph node. Omission of axillary lymph node dissection could be proposed in patients presenting a sentinel lymph node with a cytokeratin 19 mRNA copy number <2000 and a Luminal tumor phenotype.
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy. buglioni@ifo.it
authors.forename: Simonetta
authors.initials: S
authors.lastname: Buglioni
authors.forename: Franco
authors.initials: F
authors.lastname: Di Filippo
authors.forename: Irene
authors.initials: I
authors.lastname: Terrenato
authors.forename: Beatrice
authors.initials: B
authors.lastname: Casini
authors.forename: Enzo
authors.initials: E
authors.lastname: Gallo
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Marandino
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Maini
authors.forename: Rossella
authors.initials: R
authors.lastname: Pasqualoni
authors.forename: Claudio
authors.initials: C
authors.lastname: Botti
authors.forename: Simona
authors.initials: S
authors.lastname: Di Filippo
authors.forename: Edoardo
authors.initials: E
authors.lastname: Pescarmona
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001365:Axilla; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053539:Keratin-19 / Q000235:genetics; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000235:genetics / Q000503:physiopathology; D008875:Middle Aged; D061206:Neoplasm Micrometastasis / Q000235:genetics / Q000503:physiopathology; D011446:Prospective Studies; D021701:Sentinel Lymph Node Biopsy
chemical_list: D053539:Keratin-19