title: Gene expression profiling of peritoneal metastases from appendiceal and colon cancer demonstrates unique biologic signatures and predicts patient outcomes.
abstract: BACKGROUND
  Treatment of peritoneal metastases from appendiceal and colon cancer with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) shows great promise. Although long-term disease-free survival is achieved in some cases with this procedure, many patients have recurrence. Oncologists have treated such recurrences of appendiceal cancer similarly to colorectal carcinoma, which has been largely ineffective. This study uses gene expression analysis of peritoneal metastases to better understand these neoplasms.
  
  
  METHODS
  From a prospectively maintained database and tissue bank, 41 snap frozen samples of peritoneal metastases (26 appendiceal, 15 colorectal) from patients undergoing HIPEC with complete cytoreduction and more than 3 years of follow-up underwent global gene expression analysis. Distinct phenotypes were identified using unsupervised hierarchical clustering based on differential gene expression. Survival curves restratified by genotype were generated.
  
  
  RESULTS
  Three distinct phenotypes were found, 2 consisting of predominantly low grade appendiceal samples (10 of 13 in Cluster 1 and 15 of 20 in Cluster 2) and 1 consisting of predominantly colorectal samples (7 of 8 in Cluster 3). Cluster 1 consisted of patients with good prognosis and Clusters 2 and 3 consisted of patients with poor prognosis (p = 0.006). Signatures predicted survival of low- (Cluster 1) vs high-risk (Cluster 2) appendiceal (p = 0.04) and low-risk appendiceal (Cluster 1) vs colon primary (Cluster 3) (p = 0.0002).
  
  
  CONCLUSIONS
  This study represents the first use of gene expression profiling for appendiceal cancer, and demonstrates genomic signatures quite distinct from colorectal cancer, confirming their unique biology. Consequently, therapy for appendiceal lesions extrapolated from colonic cancer regimens may be unfounded. These phenotypes may predict outcomes guiding patient management.
authors.affiliation: Surgical Oncology Service, Department of General Surgery, Wake Forest University, Winston-Salem, NC 27157, USA. elevine@wakehealth.edu
authors.forename: Edward A
authors.initials: EA
authors.lastname: Levine
authors.forename: Dan G
authors.initials: DG
authors.lastname: Blazer
authors.forename: Mickey K
authors.initials: MK
authors.lastname: Kim
authors.forename: Perry
authors.initials: P
authors.lastname: Shen
authors.forename: John H
authors.initials: JH
authors.lastname: Stewart
authors.forename: Cynthia
authors.initials: C
authors.lastname: Guy
authors.forename: David S
authors.initials: DS
authors.lastname: Hsu
mesh_terms: D001063:Appendiceal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D020411:Oligonucleotide Array Sequence Analysis; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D005819:Genetic Markers