Abstract
Background:Three molecular pathways are described as the genetic basis of colorectal tumorigenesis. Among these, microsatellite instability (MSI) has shown greatest promise in serving as a biomarker to determine disease aggression by tumour biology, recurrence, and response to chemotherapy. Methodology:This prospective observational pilot study included patients of colorectal cancers, in a population subset coming to a tertiary care hospital in northern India, who were operated with curative or palliative intent over a period of one year and followed up for a maximum of 55 months. The post-operative pathological assessment was done for MSI status using PCR technique, and an attempt was made to evaluate its correlation with conventional clinical and histological parameters, early recurrences, disease-free survival and overall survival in comparison to MSS type tumours in sporadic cases of colorectal malignancies. Results:Out of 38 patients of colorectal cancer, 26 were included in the study. Male to female ratio was 7:6 (n=14:12). Mean age of presentation was 48±14.2 years. Incidence of MSI was n=4 (15.4%). On subgroup analysis, age of presentation (p=0.044) and evidence of perineural invasion (p=0.017) was found to have significant statistical association with MSI tumour biology. Recurrence was seen in seven of the seventeen patients who previously had no synchronous or metastatic disease (41.2%). The mean disease-free survival for MSS was 21.32 months and was 25.25 months for MSI group which was statistically insignificant (p = 0.277). Out of four MSI tumour biology patients one was alive and without recurrence at 47 months. While the other two were alive and without recurrence till 27 months of follow-up. Conclusion:Age and perineural invasion showed statistically significant association with MSI tumour biology. Due to the small sample size statistical significance was not established with site, recurrence rate, DFS and OS.
Highlights
Three molecular pathways are described as the genetic basis of colorectal tumorigenesis
Asian Pacific Journal of Cancer Prevention, Vol 22 2279. This prospective observational pilot study was undertaken to determine the incidence of microsatellite instability (MSI) positivity, its correlation with conventional clinical and histological parameters, early recurrence, disease free survival and overall survival as compared to microsatellite stable tumours, in cases of sporadic colorectal cancers, in a population subset coming to a tertiary care hospital in northern India
The chromosomal instability (CIN) pathway characterised by the Adenomatous Polyposis Coli (APC) gene mutation was one of the earliest described models (Fearon and Vogelstein, 1990), and ascribes to both inherited and
Summary
Three molecular pathways are described as the genetic basis of colorectal tumorigenesis. With loss of MMR function, insertion/deletion loops are not repaired, resulting in the variable expansion or contraction of microsatellites This phenomenon is referred to as Microsatellite instability (MSI) (Fujiwara et al, 1998; Horvat et al, 2011). MSI is detected in about 15% of all colorectal cancers; 3% of these are associated with Lynch syndrome and the other 12% are sporadic (Lynch et al, 2002; Popat et al, 2005) This prospective observational pilot study was undertaken to determine the incidence of MSI positivity, its correlation with conventional clinical and histological parameters, early recurrence, disease free survival and overall survival as compared to microsatellite stable tumours, in cases of sporadic colorectal cancers, in a population subset coming to a tertiary care hospital in northern India
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