title: Colorectal cancer in the very young: a comparative study of tumor markers, pathology and survival in early onset and adult onset patients.
abstract: BACKGROUND
  Colorectal cancer (CRC) diagnosed before age 30 years is a fatal disease whose biology remains poorly understood. To understand its pathogenesis, we compared molecular and clinical data in surgically treated early-age onset and adult onset patients.
  
  
  METHODS
  Clinical data and tumor tissue were collected retrospectively for 94 patients with early-age onset CRC (age ≤30 years) and compared to 275 adult CRC patients (age ≥50 years). Tumor morphology, microsatellite instability (MSI) and stability (MSS), KRAS and BRAF mutations, and mismatch repair (MMR) expression (MSH2, MLH1, MSH6, PMS2) were assessed.
  
  
  RESULTS
  Early-age CRC was distinguished from adult CRC by advanced stage presentation (P<0.001), frequent high grade cancers (P<0.001), and poor prognosis (P<0.001). MSI was associated with favorable survival and MMR loss in both groups. Compared to adults, MSI in early-onset CRC was more prevalent (P<0.01), not tightly linked to MLH1/PMS2 loss, and never associated with BRAFV600E mutations (P<0.01). MSS/BRAFV600E genotype had poor prognosis and was more prevalent in early-age CRC (9% vs. 3%).
  
  
  CONCLUSIONS
  Specific genetic subtypes are found at different frequencies in early-age onset and adult onset CRC. Complete absence of the indolent MSI/BRAFV600E genotype and enrichment in the unfavorable MSS/BRAFV600E genotype help explain the poor prognosis of early onset CRC.
authors: Section of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, CT, United States; Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States. Electronic address: sajid.khan@yale.edu.
authors: Sajid A
authors: SA
authors: Khan
authors: School of Surgery and Pathology, University of Western Australia, Nedlands, Western Australia, Australia.
authors: Melinda
authors: M
authors: Morris
authors: Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
authors: Kamran
authors: K
authors: Idrees
authors: Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
authors: Mark I
authors: MI
authors: Gimbel
authors: Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
authors: Shoshana
authors: S
authors: Rosenberg
authors: Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
authors: Zhaoshi
authors: Z
authors: Zeng
authors: Yale Center for Analytic Sciences, Yale University School of Medicine, New Haven, CT, United States.
authors: Fangyong
authors: F
authors: Li
authors: Yale Center for Analytic Sciences, Yale University School of Medicine, New Haven, CT, United States.
authors: Geliang
authors: G
authors: Gan
authors: Colorectal Service, Department of Pathology, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
authors: Jinru
authors: J
authors: Shia
authors: Pediatric Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
authors: Michael P
authors: MP
authors: LaQuaglia
authors: Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
authors: Philip B
authors: PB
authors: Paty
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D053843:DNA Mismatch Repair; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: BRAF; Early onset colorectal cancer; MSI