Abstract
Purpose Microsatellite instability (MSI) caused by mismatch repair protein (MMRP) deficiency is detected in 15% of sporadic colorectal cancers (CRCs). Our aim is to investigate the frequency of MMRP deficiency in young CRC patients, using immunohistochemical analysis. Methods This study targeted cases of CRC at King Hussein Cancer Center from 2004 until 2012 in patients 45 years of age or younger at the time of diagnosis. Clinicopathological data was obtained from 155 patients' records. Immunohistochemistry for MLH1, MSH2, PMS2, and MSH6 proteins was performed on paraffin-embedded tissue containing carcinoma. Results The median age of patient at diagnosis was 38 years. A total of 29 (19%) cases showed deficient MMRP(dMMRP)expression. Loss of expression of PMS2 was seen in 17 cases, 12 cases of which showed loss of MLH1 expression. Loss of expression of MSH6 was seen in 10 cases, 9 of which showed loss of MSH2 expression. One case (3.4%) showed loss of all four MMR proteins, and another case (3.4%) showed loss of PMS2/MLH1 and MSH6. There was a significant association between abnormal MMR protein expression and tumor location proximal to splenic flexure (p value 0.000), pathologic features suggestive of microsatellite instability (p value 0.000), P53 negativity (p value 0.000), and stage (p value 0.02). Patients with dMMRP CRC appeared to have a significantly better overall survival compared to patients with proficient MMRP(pMMRP)(p value 0.02). Loss of MSH2/MSH6 was significantly associated with positive family history of cancer (p value = 0.020). Conclusions The prevalence of dMMRP tumors in this age group appears to be similar to international literature. dMMRP tumors tends to be associated with earlier stages and better outcomes compared to pMMRP cases. dMMRP can serve as a biomarker for better prognosis. These results are of value in directing the clinical management of young patients with CRC.
Highlights
Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide
We investigate the prevalence of dMMRP in young patients with CRC and describe patients’ and tumors’ characteristics and outcome in comparison to pMMRP tumors in the same age group
Eighty three (54%) patients were male, and male to female ratio was 1.15 : 1. Most tumors included in the study were located in the rectum (47%), with 15%, 11%, and 25% located in the right, left, and sigmoid colon, respectively
Summary
Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. Registry (JNCR) report in 2016, there were 641 colorectal cancer cases, accounting for 10.7% of all newly diagnosed cases among Jordanians. It ranked the second among all new cancers in both genders, the first among males and the second among females [2]. With a median age of 68 years in men and 72 in women for colon cancer and 63 years for rectal cancer in both men and women, and as CRC incidence increases significantly beyond the fifth decade of life, screening is usually not Gastroenterology Research and Practice recommended for individuals at an average risk younger than 45 years [3, 4]. In contrast to the noticed decline in CRC mortality among adults aged 55 years and older, there is about 11% increase in mortality among adults younger than 55 years [4]
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