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. 2016 Nov;51(11):1812-1817.
doi: 10.1016/j.jpedsurg.2016.07.015. Epub 2016 Aug 5.

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

Sajid A Khan  1 , Melinda Morris  2 , Kamran Idrees  3 , Mark I Gimbel  3 , Shoshana Rosenberg  3 , Zhaoshi Zeng  3 , Fangyong Li  4 , Geliang Gan  4 , Jinru Shia  5 , Michael P LaQuaglia  6 , Philip B Paty  3
Affiliations

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

Sajid A Khan et al. J Pediatr Surg. 2016 Nov.

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.

Keywords: BRAF; Early onset colorectal cancer; MSI.

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Figures

Figure 1
Figure 1
Disease-specific survival according to age, microsatellite genotype and microsatellite genotype in relation to BRAF mutational status. a. Disease-specific survival of early-age onset colorectal cancer compared to adult onset colorectal cancer patients. 5-year disease-specific survival in the early-age onset group is worse compared to the adult onset group (48% vs. 78%, P<0.001). b. Disease-specific survival in adult-age onset colorectal cancer patients according to microsatellite instability (MSI) and microsatellite stability (MSS). MSI genotype was associated with a favorable 5-year disease-specific survival (93% vs. 73%, P=0.006). c. Disease-specific survival in early-age onset colorectal cancer patients according to microsatellite instability (MSI) and microsatellite stability (MSS). MSI genotype was associated with a favorable 5-year disease-specific survival (65% vs. 39%, P=0.048). d. Disease-specific survival in early-age onset group with microsatellite stability (MSS) phenotype stratified according to BRAF mutational status. 5-year disease-specific survival trended worse in patients possessing the MSS/BRAFV600Emut genotype compared to the MSS/BRAF wild-type (WT) genotype (16% vs. 42%, p=0.23). e. Disease-specific survival of adult onset-MSI genotype compared to early-age onset-MSI genotype in colorectal cancer patients. Both adult and early-age onset MSI were associated with favorable survivals, though adult-MSI genotype was associated with a more favorable 5-year disease-specific survival (93% vs. 65%, P=0.01).
Figure 1
Figure 1
Disease-specific survival according to age, microsatellite genotype and microsatellite genotype in relation to BRAF mutational status. a. Disease-specific survival of early-age onset colorectal cancer compared to adult onset colorectal cancer patients. 5-year disease-specific survival in the early-age onset group is worse compared to the adult onset group (48% vs. 78%, P<0.001). b. Disease-specific survival in adult-age onset colorectal cancer patients according to microsatellite instability (MSI) and microsatellite stability (MSS). MSI genotype was associated with a favorable 5-year disease-specific survival (93% vs. 73%, P=0.006). c. Disease-specific survival in early-age onset colorectal cancer patients according to microsatellite instability (MSI) and microsatellite stability (MSS). MSI genotype was associated with a favorable 5-year disease-specific survival (65% vs. 39%, P=0.048). d. Disease-specific survival in early-age onset group with microsatellite stability (MSS) phenotype stratified according to BRAF mutational status. 5-year disease-specific survival trended worse in patients possessing the MSS/BRAFV600Emut genotype compared to the MSS/BRAF wild-type (WT) genotype (16% vs. 42%, p=0.23). e. Disease-specific survival of adult onset-MSI genotype compared to early-age onset-MSI genotype in colorectal cancer patients. Both adult and early-age onset MSI were associated with favorable survivals, though adult-MSI genotype was associated with a more favorable 5-year disease-specific survival (93% vs. 65%, P=0.01).
Figure 1
Figure 1
Disease-specific survival according to age, microsatellite genotype and microsatellite genotype in relation to BRAF mutational status. a. Disease-specific survival of early-age onset colorectal cancer compared to adult onset colorectal cancer patients. 5-year disease-specific survival in the early-age onset group is worse compared to the adult onset group (48% vs. 78%, P<0.001). b. Disease-specific survival in adult-age onset colorectal cancer patients according to microsatellite instability (MSI) and microsatellite stability (MSS). MSI genotype was associated with a favorable 5-year disease-specific survival (93% vs. 73%, P=0.006). c. Disease-specific survival in early-age onset colorectal cancer patients according to microsatellite instability (MSI) and microsatellite stability (MSS). MSI genotype was associated with a favorable 5-year disease-specific survival (65% vs. 39%, P=0.048). d. Disease-specific survival in early-age onset group with microsatellite stability (MSS) phenotype stratified according to BRAF mutational status. 5-year disease-specific survival trended worse in patients possessing the MSS/BRAFV600Emut genotype compared to the MSS/BRAF wild-type (WT) genotype (16% vs. 42%, p=0.23). e. Disease-specific survival of adult onset-MSI genotype compared to early-age onset-MSI genotype in colorectal cancer patients. Both adult and early-age onset MSI were associated with favorable survivals, though adult-MSI genotype was associated with a more favorable 5-year disease-specific survival (93% vs. 65%, P=0.01).
Figure 1
Figure 1
Disease-specific survival according to age, microsatellite genotype and microsatellite genotype in relation to BRAF mutational status. a. Disease-specific survival of early-age onset colorectal cancer compared to adult onset colorectal cancer patients. 5-year disease-specific survival in the early-age onset group is worse compared to the adult onset group (48% vs. 78%, P<0.001). b. Disease-specific survival in adult-age onset colorectal cancer patients according to microsatellite instability (MSI) and microsatellite stability (MSS). MSI genotype was associated with a favorable 5-year disease-specific survival (93% vs. 73%, P=0.006). c. Disease-specific survival in early-age onset colorectal cancer patients according to microsatellite instability (MSI) and microsatellite stability (MSS). MSI genotype was associated with a favorable 5-year disease-specific survival (65% vs. 39%, P=0.048). d. Disease-specific survival in early-age onset group with microsatellite stability (MSS) phenotype stratified according to BRAF mutational status. 5-year disease-specific survival trended worse in patients possessing the MSS/BRAFV600Emut genotype compared to the MSS/BRAF wild-type (WT) genotype (16% vs. 42%, p=0.23). e. Disease-specific survival of adult onset-MSI genotype compared to early-age onset-MSI genotype in colorectal cancer patients. Both adult and early-age onset MSI were associated with favorable survivals, though adult-MSI genotype was associated with a more favorable 5-year disease-specific survival (93% vs. 65%, P=0.01).
Figure 1
Figure 1
Disease-specific survival according to age, microsatellite genotype and microsatellite genotype in relation to BRAF mutational status. a. Disease-specific survival of early-age onset colorectal cancer compared to adult onset colorectal cancer patients. 5-year disease-specific survival in the early-age onset group is worse compared to the adult onset group (48% vs. 78%, P<0.001). b. Disease-specific survival in adult-age onset colorectal cancer patients according to microsatellite instability (MSI) and microsatellite stability (MSS). MSI genotype was associated with a favorable 5-year disease-specific survival (93% vs. 73%, P=0.006). c. Disease-specific survival in early-age onset colorectal cancer patients according to microsatellite instability (MSI) and microsatellite stability (MSS). MSI genotype was associated with a favorable 5-year disease-specific survival (65% vs. 39%, P=0.048). d. Disease-specific survival in early-age onset group with microsatellite stability (MSS) phenotype stratified according to BRAF mutational status. 5-year disease-specific survival trended worse in patients possessing the MSS/BRAFV600Emut genotype compared to the MSS/BRAF wild-type (WT) genotype (16% vs. 42%, p=0.23). e. Disease-specific survival of adult onset-MSI genotype compared to early-age onset-MSI genotype in colorectal cancer patients. Both adult and early-age onset MSI were associated with favorable survivals, though adult-MSI genotype was associated with a more favorable 5-year disease-specific survival (93% vs. 65%, P=0.01).
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