title: Prognostic significance and molecular associations of tumor growth pattern in colorectal cancer.
abstract: BACKGROUND
  Infiltrative growth pattern at the tumor margin has been associated with shorter patient survival. However, little is known about the prognostic significance of tumor growth pattern, independent of tumoral molecular alterations and other histologic features.
  
  
  METHODS
  Utilizing a database of 1139 colon and rectal cancer patients in two prospective cohort studies, histologic features including tumor growth pattern, tumor differentiation, lymphocytic reaction, mucinous component, and signet ring cell component were recorded by a single pathologist. Cox proportional hazard model was used to compute mortality hazard ratio, adjusting for clinical, pathologic, and tumor molecular features, including microsatellite instability, the CpG island methylator phenotype, long interspersed nucleotide element 1 (LINE-1) methylation, and KRAS, BRAF, and PIK3CA mutations.
  
  
  RESULTS
  Among 1139 colorectal cancers, we observed expansile growth pattern in 372 tumors (33%), intermediate growth pattern in 610 tumors (54%), and infiltrative growth pattern in 157 tumors (14%). Compared to patients with expansile growth pattern, those with infiltrative growth pattern experienced shorter cancer-specific survival (log rank P < 0.0001; multivariate hazard ratio 1.74; 95% confidence interval 1.22-2.47) and overall survival (log rank P < 0.0001; multivariate hazard ratio 1.78; 95% confidence interval 1.33-2.39). The prognostic association of infiltrative growth pattern was confined to patients with stage I-III disease (P (interaction) with stage = 0.0001).
  
  
  CONCLUSIONS
  Infiltrative growth pattern was associated with worse prognosis among stage I-III colorectal cancer patients, independent of other clinical, pathologic, and molecular characteristics.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. tmorikawa-tky@umin.ac.jp
authors.forename: Teppei
authors.initials: T
authors.lastname: Morikawa
authors.forename: Aya
authors.initials: A
authors.lastname: Kuchiba
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
authors.forename: Jason L
authors.initials: JL
authors.lastname: Hornick
authors.forename: Mai
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Yu
authors.initials: Y
authors.lastname: Imamura
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liao
authors.forename: Reiko
authors.initials: R
authors.lastname: Nishihara
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meyerhardt
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D018279:Carcinoma, Signet Ring Cell / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D053842:Microsatellite Instability; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor