title: Sentinel node tumour burden quantified based on cytokeratin 19 mRNA copy number predicts non-sentinel node metastases in breast cancer: molecular whole-node analysis of all removed nodes.
abstract: OBJECTIVE
  The one-step nucleic acid amplification (OSNA) assay can assess an entire lymph node and detect clinically relevant metastases quantified based on cytokeratin 19 (CK19) mRNA copy number. The OSNA assay of all sentinel lymph nodes (SNs) and non-sentinel nodes (non-SNs) allows for the accurate measurement of tumour burden in either situation. We aim to reveal the usefulness of the OSNA assay regarding the prediction of non-SN metastasis.
  
  
  METHODS
  The subjects consisted of 185 breast cancer patients who underwent axillary dissection after a metastatic SN biopsy and whose SNs and non-SNs were examined using the OSNA whole-node assay between 2009 and 2011. The non-SN tumour burden was classified as macrometastasis (CK19 mRNA ≥ 5000 copies/μl) or micrometastasis (250-5000 copies/μl). The relationship between SN and non-SN tumour burdens and predictors of non-SN metastasis were investigated.
  
  
  RESULTS
  Among these 185 patients, 38 patients (20.5%) had macrometastasis and 58 (31.4%) had micrometastasis only in the non-SNs. Non-SN macrometastasis rates increased in direct proportion to the SN copy number: approximately 5% in patients with SNs with 250-500 copies; 20%, 500-5000 copies and 30%, ≥ 5000 copies. However, non-SN micrometastasis rates were approximately 30% regardless of the SN copy number. In multivariate analyses, the mean SN copy number, number of macrometastatic SN and lymphovascular invasion were significant for identifying non-SN macrometastases.
  
  
  CONCLUSIONS
  The SN tumour burden quantified using the OSNA assay predicts non-SN metastases. A novel mathematical model to predict the non-SN tumour burden can be generated using the results of the OSNA assay.
authors.affiliation: Division of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo 135-8550, Japan. tomo.osako@jfcr.or.jp
authors.forename: Tomo
authors.initials: T
authors.lastname: Osako
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwase
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Kimura
authors.forename: Rie
authors.initials: R
authors.lastname: Horii
authors.forename: Futoshi
authors.initials: F
authors.lastname: Akiyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D006801:Humans; D053534:Keratin-9 / Q000235:genetics*; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D021141:Nucleic Acid Amplification Techniques; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy; D047368:Tumor Burden / Q000235:genetics
chemical_list: D053534:Keratin-9; D012333:RNA, Messenger