title: Molecularly determined total tumour load in lymph nodes of stage I-II colon cancer patients correlates with high-risk factors. A multicentre prospective study.
abstract: Stage I-II (pN0) colorectal cancer patients are surgically treated although up to 25 % will eventually die from disease recurrence. Lymph node (LN) status is an independent prognostic factor in colorectal cancer (CRC), and molecular tumour detection in LN of early-stage CRC patients is associated with an increased risk of disease recurrence and poor survival. This prospective multicentre study aimed to determine the relationship between LN molecular tumour burden and conventional high-risk factors in stage I-II colon cancer patients. A total of 1940 LN from 149 pathologically assessed pN0 colon cancer patients were analysed for the amount of tumour cytokeratin 19 (CK19) messenger RNA (mRNA) with the quantitative reverse transcription loop-mediated isothermal amplification molecular assay One-Step Nucleic Acid Amplification. Patient's total tumour load (TTL) resulted from the sum of all CK19 mRNA tumour copies/μL of each positive LN from the colectomy specimen. A median of 15 LN were procured per case (IQR 12;20). Molecular positivity correlated with high-grade (p < 0.01), mucinous/signet ring type (p = 0.017), male gender (p = 0.02), number of collected LN (p = 0.012) and total LN weight per case (p < 0.01). The TTL was related to pT stage (p = 0.01) and tumour size (p < 0.01) in low-grade tumours. Multivariate logistic regression showed independent correlation of molecular positivity with gender, tumour grade and number of fresh LN [AUC = 0.71 (95 % CI = 0.62-0.79)]. Our results show that lymph node CK19 mRNA detection correlates with classical high-risk factors in stage I-II colon cancer patients. Total tumour load is a quantitative and objective measure that may help to better stage early colon cancer patients.
authors.affiliation: Pathology Department, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, University of Barcelona, Escala 3, Planta 5. Villarroel 170, Barcelona, 08036, Spain.
authors.forename: Iban
authors.initials: I
authors.lastname: Aldecoa
authors.affiliation: Pathology Department, Alava University Hospital, Vitoria-Gasteiz, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Atares
authors.affiliation: Pathology Department, Hospital Arnau de Vilanova, Lleida, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Tarragona
authors.affiliation: Pathology Department, Hospital L. Alcanyis, Xativa, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Bernet
authors.affiliation: Surgery Department, Alava University Hospital, Txagorritxu, Spain.
authors.forename: Jose Domingo
authors.initials: JD
authors.lastname: Sardon
authors.affiliation: Pathology Department, Hospital Costa del Sol, Marbella, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pereda
authors.affiliation: Pathology Department, Hospital Reina Sofia, Cordoba, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Villar
authors.affiliation: Pathology Department, Hospital Severo Ochoa, Leganes, Madrid, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Mendez
authors.affiliation: Pathology Department, Hospital Severo Ochoa, Leganes, Madrid, Spain.
authors.forename: Elvira
authors.initials: E
authors.lastname: Gonzalez-Obeso
authors.affiliation: Pathology Department, Hospital Onkologikoa, San Sebastian, Spain.
authors.forename: Kepa
authors.initials: K
authors.lastname: Elorriaga
authors.affiliation: Pathology Department, Hospital 12 Octubre, Madrid, Spain.
authors.forename: Guadalupe Lopez
authors.initials: GL
authors.lastname: Alonso
authors.affiliation: Biostatistic Unit, Hospital Ramon y Cajal, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Zamora
authors.affiliation: Gastroenterology Department and Bioinformatics Unit, CIBERehd, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Planell
authors.affiliation: Pathology Department, Hospital Ramon y Cajal, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Palacios
authors.affiliation: Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.affiliation: Pathology Department, Hospital Arnau de Vilanova, Lleida, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
authors.affiliation: Pathology Department, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, University of Barcelona, Escala 3, Planta 5. Villarroel 170, Barcelona, 08036, Spain. mcuatrec@clinic.ub.es.|CIBERehd, and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain. mcuatrec@clinic.ub.es.
authors.forename: Miriam
authors.initials: M
authors.lastname: Cuatrecasas
mesh_terms: D000368:Aged; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000473:pathology*; D009367:Neoplasm Staging / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D047368:Tumor Burden
keywords: Colorectal neoplasms; Cytokeratin 19; Lymph nodes; Molecular pathology; Neoplasm staging