North Pacific Surgical Association
Stage III & IV colon and rectal cancers share a similar genetic profile: a review of the Oregon Colorectal Cancer Registry

https://doi.org/10.1016/j.amjsurg.2013.01.029Get rights and content

Abstract

Background

Determining the molecular profile of colon and rectal cancers offers the possibility of personalized cancer treatment. The purpose of this study was to determine whether known genetic mutations associated with colorectal carcinogenesis differ between colon and rectal cancers and whether they are associated with survival.

Methods

The Oregon Colorectal Cancer Registry is a prospectively maintained, institutional review board–approved tissue repository with associated demographic and clinical information. The registry was queried for any patient with molecular analysis paired with clinical data. Patient demographics, tumor characteristics, microsatellite instability status, and mutational analysis for p53, AKT, BRAF, KRAS, MET, NRAS, and PIK3CA were analyzed. Categorical variables were compared using chi-square tests. Continuous variables between groups were analyzed using Mann-Whitney U tests. Kaplan-Meier analysis was used for survival studies. Comparisons of survival were made using log-rank tests.

Results

The registry included 370 patients: 69% with colon cancer and 31% with rectal cancer. Eighty percent of colon cancers and 68% of rectal cancers were stages III and IV. Mutational analysis found no significant differences in detected mutations between colon and rectal cancers, except that there were significantly more BRAF mutations in colon cancers compared with rectal cancers (10% vs 0%, P < .008). No differences were seen in 5-year survival rates of patients with colon versus rectal cancers when stratified by the presence of KRAS, PIK3CA, and BRAF mutations.

Conclusions

Stage III and IV colon and rectal cancers share similar molecular profiles, except that there were significantly more BRAF mutations in colon cancers compared with rectal cancers.

Section snippets

Patient information, microsatellite instability, and mutation analysis

An institutional review board–approved study was performed, using the Oregon Colorectal Cancer Registry (OCCR). Patient demographics and tumor characteristics, including MSI and mutations for p53, AKT, BRAF, KRAS, MET, NRAS, and PIK3CA, were analyzed in up to 386 patients. Not all patients had every mutation tested. Mutations were tested on the basis of clinical suspicion by the pathologist or medical oncologist.

Tumor specimens and DNA preparation

Blocks of formalin-fixed, paraffin-embedded tumor tissue, or unstained sections of

Demographics

Using the OCCR, we identified 386 potential patients to include in our study. One hundred sixteen patients (31%) had rectal cancer, and 254 (69%) had colon cancer. The status of the remaining 16 patients was indeterminate. Colon cancers were equally distributed between men and women (49% vs 51%), but rectal cancers were more common in men than in women (66% vs 34%). Three hundred forty-five patients were staged, using the 7th edition of the American Joint Committee on Cancer's

Comments

The purpose of this study was to determine whether known genetic mutations associated with colorectal carcinogenesis differ between colon and rectal cancers and if differences were associated with survival independent of stage. Using the OCCR database, we demonstrated that there were no significant differences in the prevalence of MSI and mutations for p53, KRAS, PIK3CA, AKT, MET, and NRAS in stage III and IV colon and rectal cancers. However, similar to studies in early-stage colorectal

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The authors declare no conflicts of interest.

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