title: Association between the cytogenetic profile of tumor cells and response to preoperative radiochemotherapy in locally advanced rectal cancer.
abstract: Neoadjuvant radiochemotherapy to locally advanced rectal carcinoma patients has proven efficient in a high percentage of cases. Despite this, some patients show nonresponse or even disease progression. Recent studies suggest that different genetic alterations may be associated with sensitivity versus resistance of rectal cancer tumor cells to neoadjuvant therapy. We investigated the relationship between intratumoral pathways of clonal evolution as assessed by interphase fluorescence in situ hybridization (51 different probes) and response to neoadjuvant radiochemotherapy, evaluated by Dworak criteria in 45 rectal cancer tumors before (n = 45) and after (n = 31) treatment. Losses of chromosomes 1p (44%), 8p (53%), 17p (47%), and 18q (38%) and gains of 1q (49%) and 13q (75%) as well as amplification of 8q (38%) and 20q (47%) chromosomal regions were those specific alterations found at higher frequencies. Significant association (P < 0.05) was found between alteration of 1p, 1q, 11p, 12p, and 17p chromosomal regions and degree of response to neoadjuvant therapy. A clear association was observed between cytogenetic profile of the ancestral tumor cell clone and response to radiochemotherapy; cases presenting with del(17p) showed a poor response to neoadjuvant treatment (P = 0.03), whereas presence of del(1p) was more frequently observed in responder patients (P = 0.0002). Moreover, a significantly higher number of copies of chromosomes 8q (P = 0.004), 13q (P = 0.003), and 20q (P = 0.002) were found after therapy versus paired pretreatment rectal cancer samples. Our results point out the existence of an association between tumor cytogenetics and response to neoadjuvant therapy in locally advanced rectal cancer. Further studies in larger series of patients are necessary to confirm our results.
authors.affiliation: From the Servicio General de Citometría, Departamento de Medicina and Centro de Investigación del Cáncer (IBMCC-CSIC/USAL), Hospital Universitario de Salamanca-IBSAL, Universidad de Salamanca (MG-G, MLG, MF, AO, MS); Servicio de Cirugía General y Aparato digestivo (JC, JAA, LMG, LM-B); Servicio de Patología, (OB, MMA, AS-B, OB); Servicio de Radio-diagnóstico, Hospital Universitario de Salamanca-IBSAL (MM); and Servicio de Oncología Radioterápica, Hospital Universitario de Salamanca (AR), Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: González-González
authors.forename: Jacinto
authors.initials: J
authors.lastname: Garcia
authors.forename: José A
authors.initials: JA
authors.lastname: Alcazar
authors.forename: María L
authors.initials: ML
authors.lastname: Gutiérrez
authors.forename: Luis M
authors.initials: LM
authors.lastname: Gónzalez
authors.forename: Oscar
authors.initials: O
authors.lastname: Bengoechea
authors.forename: María M
authors.initials: MM
authors.lastname: Abad
authors.forename: Angel
authors.initials: A
authors.lastname: Santos-Briz
authors.forename: Oscar
authors.initials: O
authors.lastname: Blanco
authors.forename: Manuela
authors.initials: M
authors.lastname: Martín
authors.forename: Ana
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Manuel
authors.initials: M
authors.lastname: Fuentes
authors.forename: Luis
authors.initials: L
authors.lastname: Muñoz-Bellvis
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Jose M
authors.initials: JM
authors.lastname: Sayagues
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000069287:Capecitabine; D059186:Chemoradiotherapy, Adjuvant; D002869:Chromosome Aberrations; D060965:Clonal Evolution; D015331:Cohort Studies; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil