title: Effect of High-Grade Disease on Outcomes of Surgically Treated Colon Cancer.
abstract: BACKGROUND
  Tumor grade is one of the cardinal pathological characteristics of colon cancer. Despite a large body of evidence on disease grade in general, the exact impact of high-grade disease in the context of the simplified high/low-grade dichotomy that is based on glandular formation rate has yet to be quantified.
  
  
  METHODS
  Patients with sporadic colon cancer treated surgically at our center (2004-2011) were included in an institutional review board-approved database. We measured the rates of distant and nodal disease spread in baseline pathology and the multivariable hazard radio (mHR) of recurrence and overall- and disease-specific mortality.
  
  
  RESULTS
  Among 922 patients with specified tumor grade in baseline surgical pathology, 175 (19.0 %) had high-grade disease. These patients were at far higher risk of lymph node metastasis (63.8 vs. 39.6 %; P < 0.001) and metastatic presentation (31.4 vs. 15.8 %; P < 0.001). These baseline differences also led to significantly worse outcomes, including disease recurrence (17.1 vs. 10.6 %; mHR = 1.83; P = 0.026), overall mortality (57.7 vs. 33.3 %; mHR = 1.65; P < 0.001), and colon cancer-specific mortality (39.4 vs. 16.9 %; mHR = 1.57; P = 0.004). Most significantly, in stage II patients (n = 294), those with high-grade disease (16.0 %) had an mHR of 2.84 (P < 0.001) for mortality.
  
  
  CONCLUSIONS
  High-grade disease on baseline surgical pathology is associated with a considerably higher rate of nodal and distant metastasis in colon cancer. As a result, the colon cancer-related mortality doubles for patients with high-grade disease. These findings were independent of baseline staging and confirm that the high-/low-grade tumor dichotomy is an important prognostic factor greatly influencing colon cancer outcomes across stages.
authors.affiliation: Division of General Surgery & Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ramzi
authors.initials: R
authors.lastname: Amri
authors.affiliation: Division of General Surgery & Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Liliana G
authors.initials: LG
authors.lastname: Bordeianou
authors.affiliation: Division of General Surgery & Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. dberger@mgh.harvard.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Berger
mesh_terms: D000368:Aged; D003110:Colonic Neoplasms / Q000473:pathology* / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate