A relationship to survival is seen by combining the factors of mismatch repair status, tumor location and age of onset in colorectal cancer patients

Abstract

BackgroundThe progression of colorectal cancer (CRC) may differ depending on the location of the tumor and the age of onset of the disease. Previous studies also suggested that the molecular basis of CRC varies with tumor location, which could affect the clinical management of patients. Therefore, we performed survival analysis looking at different age groups and mismatch repair status (MMR) of CRC patients according to primary tumor location in an attempt to identify subgroups of CRC that might help in the prognosis of disease.MethodsA group of 2233 patients operated on to remove their CRC tumors were analyzed (521 with right colon cancer, 740 with left colon cancer and 972 with rectal cancer). The expression of four MMR genes was assessed by immunohistochemistry (IHC), independent of clinical criteria. From the data collected, a predictive model for overall survival (OS) could be constructed for some associations of tumor location and age of onset using Kaplan-Meier, logistic and Cox regression analysis.ResultsWhen tumor location was considered as the lone factor, we found no statistical difference in overall survival (OS) between right cancer (68%), left cancer (67%) or rectal cancer tumor locations (71%) (HR: 1.17, 95%CI (confidence interval): 0.97–1.43, P = 0.057). When age of onset was considered, middle age (40–59 years) and older (60–85 years) patients were found to have higher OS than younger onset cancer (20–39 years) patients (69% vs 71% vs 59%, HR: 1.07, 95% confidence interval (CI): 0.91–1.25, P = 0.008). When both age of onset and tumor location were considered in combination as disease factors, we found that the subgroup of patients with left colon cancer from middle age (69%) and older (67%) aged patients had higher OS than younger (54%) patients (HR: 0.89, 95%CI: 0.68–1.16, P = 0.048). However in patients with right colon cancers, we found no statistical difference is OS between younger, middle age or older grouped patients (60% vs 71% vs 67%, HR: 0.84, 95% CI: 0.61–1.16, P = 0.194). With regard to rectal located cancers, we found that younger (62%) and middle age (68) patients had lower OS than older (77%) patients (HR:1.46, 95%CI: 1.13–1.88, P = 0.004). The rates of deficient MMR (dMMR) was 10.4%. We found no statistical difference in OS stratified by tumor locations. However, right colon cancer patients with dMMR (86%) had higher OS than those with proficient MMR (pMMR) (63%) (HR: 3.01, 95% CI: 1.82–4.97, P<0.001). Left colon cancer patients with dMMR (76%) also had higher OS than those with pMMR (66%) (HR: 1.67, 95% CI: 0.95–2.92, P = 0.01). Oppositely, rectal cancer patients with dMMR (60%) had lower OS than those pMMR (68%) (HR: 0.77, 95% CI: 0.51–1.17, P = 0.04).ConclusionsThese data demonstrate that primary tumor location can be an important factor when considered along with age of onset for the prognosis of CRC. Primary tumor location is also an important factor to evaluate the predictive effect of MMR status for the prognosis of CRC.

Cytolytic Activity Score to Assess Anticancer Immunity in Colorectal Cancer

“…Since CAS measures intra-tumoral immune cytolytic activity, it makes sense to see high CAS associating with high TIL conditions such as MSI-H CRC. Patients with MSI-H tumors have also been found in several studies to have improved survival compared to their MSS counterparts 1,5 . This may be attributed to the elevation in cytolytic activity within their cancer cells secondary to increased TIL infiltration.…”

“…Colorectal cancer (CRC) is the fourth most common cause of cancer related death 1,2 . Impaired DNA repair mechanisms and genomic instability are key factors in carcinogenesis via the accumulation of somatic mutations within DNA 2,3 .…”

Differences in the immunosurveillance pattern associated with DNA mismatch repair status between right‐sided and left‐sided colorectal cancer

“…[14][15][16] In general, dMMR is more frequent in right-sided CC than in left-sided CRC and is associated with better survival than pMMR. 17 Therefore, this study aimed to investigate the clinicopathologic differences according to the immunosurveillance pattern between right-sided and left-sided CRC, using IHC staining of MMR proteins to identify biomarkers and prognostic factors.…”

Gene expression analyses identify a relationship between stanniocalcin 2 and the malignant behavior of colorectal cancer

“… 21 , 22 For instance, it was reported that microsatellite-stable (MSS) CRC had a distinct phenotype such as left-sided location. 23 , 24 All of our results suggested that STC2 might contribute to the tumorigenesis or progression of CRC.…”