High MET gene copy number predicted poor prognosis in primary intestinal diffuse large B-cell lymphoma

Diagn Pathol. 2013 Feb 4:8:16. doi: 10.1186/1746-1596-8-16.

Abstract

Background: MET is a proto-oncogene with its copy number (CN) alterations been reported in some cancers, but not in primary intestinal diffuse large B-cell lymphoma (PI-DLBL) yet.

Methods: In this retrospective study, we performed histology and chart reviews, immunohistochemistry and quantitative polymerase chain reaction for MET CN alterations on 28 surgically resected PI-DLBLs.

Results: There were 12 men and 16 women with a median age of 70 and a mean follow-up of 32 months. The median MET CN was 2.20 (range, 1.04 to 3.35). CN gain was observed in 11 cases, including 5 with CN greater than 3. Nine patients (32%) had diploid CN and eight (29%) with CN loss. Patients with gain or diploid CN showed significantly worse prognosis (P = 0.046) than those with CN loss. Furthermore, MET CN greater than 3 was associated with an adverse outcome (P = 0.003). Intestinal perforation at presentation was the sole clinicopathological factor associated with a poor prognosis (P = 0.004) and perforation was correlated with CN greater than 3 (P = 0.002).

Conclusions: Our finding of MET CN gain as a poor prognostic factor in PI-DLBL patients might serve as the rationale for targeting MET signaling pathway in the treatment of these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biopsy
  • Chi-Square Distribution
  • DNA Copy Number Variations*
  • Female
  • Gene Dosage*
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Intestinal Neoplasms / chemistry
  • Intestinal Neoplasms / complications
  • Intestinal Neoplasms / genetics*
  • Intestinal Neoplasms / mortality
  • Intestinal Neoplasms / surgery
  • Intestinal Perforation / etiology
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / chemistry
  • Lymphoma, Large B-Cell, Diffuse / complications
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / surgery
  • Male
  • Middle Aged
  • Phenotype
  • Prognosis
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-met / genetics*
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Risk Factors
  • Time Factors

Substances

  • Biomarkers, Tumor
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • MET protein, human
  • Proto-Oncogene Proteins c-met