Colorectal cancer in the very young: a comparative study of tumor markers, pathology and survival in early onset and adult onset patients

Authors

Sajid A. Khan, 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.Follow
Melinda Morris, School of Surgery and Pathology, University of Western Australia, Nedlands, Western Australia, Australia.
Kamran Idrees, Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
Mark I. Gimbel, Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
Shoshana Rosenberg, Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
Zhaoshi Zeng, Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.Follow
Fangyong Li, Yale Center for Analytic Sciences, Yale University School of Medicine, New Haven, CT, United States.Follow
Geliang Gan, Yale Center for Analytic Sciences, Yale University School of Medicine, New Haven, CT, United States.
Jinru Shia, Colorectal Service, Department of Pathology, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.Follow
Michael P. LaQuaglia, Pediatric Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.
Philip B. Paty, Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, NY, New York, United States.Follow

Document Type

Article

Publication Title

Journal of pediatric surgery

Abstract

INTRODUCTION: 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. MATERIALS AND 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%). DISCUSSION: 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.

First Page

1812

Last Page

1817

DOI

10.1016/j.jpedsurg.2016.07.015

Publication Date

11-1-2016

Recommended Citation

Khan, Sajid A.; Morris, Melinda; Idrees, Kamran; Gimbel, Mark I.; Rosenberg, Shoshana; Zeng, Zhaoshi; Li, Fangyong; Gan, Geliang; Shia, Jinru; LaQuaglia, Michael P.; and Paty, Philip B., "Colorectal cancer in the very young: a comparative study of tumor markers, pathology and survival in early onset and adult onset patients" (2016). Surgery. 190.
https://scholar.bridgeporthospital.org/surgery/190

Identifier

27558481 (pubmed); NIHMS834748 (mid); PMC5312708 (pmc); 10.1016/j.jpedsurg.2016.07.015 (doi); S0022-3468(16)30197-X (pii)