Immunohistochemical Expression of MMR Proteins with Clinicopathological Correlation in Colorectal Cancer in Egypt

Abstract

BACKGROUND: Microsatellite instability (MSI) is the genetic pathway underlying 15% of sporadic colorectal carcinoma (CRC) and hereditary non-polyposis CRC. MSI-H CRC has a distinct clinicopathological characteristic including excess mucin and signet ring component, proximal colon, Crohn’s like reaction, lymphocytic infiltration, and better survival.
 AIM: This research aims to screen Egyptian CRC patients for MSI status by IHC testing of expression of the MMR proteins in correlation to its clinicopathological features.
 MATERIAL AND METHODS: Immunohistochemistry study for mismatch repair proteins (MMR) was done on 115 cases of CRC. Their expressions were assessed and correlated to clinicopathological parameters in an attempt to obtain the most significant predictors of MSI.
 RESULTS: MSI (low and high) represents 67% of the study cases. The most frequent expression pattern was combined loss of MLH, and PMS2 (38% of MSI) followed by a combined loss of MSH2, and MSH6 (29% of MSI). There was significant correlation of expression pattern of MMR proteins with the laterality, lymphovascular emboli, perineural invasion, grade, T stage, N stage, signet ring component, tumor infiltrating lymphocyte, and peritumoral lesion (0.014, 0.035, 0.012, 0.033, 0.013, 0.000, 0.041, 0.012, and 0.009 respectively). Proximal location (right sided) and lower grade, higher nodal stage, and marked TIL were selected as predictors of MS-H CRC (0.005, 0.031, 0.025, and 0.000 respectively).
 CONCLUSION: All clinicopathological and histological parameters should be assessed in CRC for the sake of predicting MSI. The optimal approach to MSI evaluation is (IHC) assessment of MMR proteins.

Microsatellite Instability and Life Style Factors in Sporadic Colorectal Cancer

“…Previous study comparing Egyptian CRC patients with Western CRC patients, found that the frequency of MSI-H tumors in the Egyptian group was higher than that in the Western sporadic group (37% vs. 13%, p = 0.002) (Soliman et al, 2001). Soliman et al, (2019) found that the expression level of MSI-H was 47.0%, which was more than 10% higher than the present results. However, many Egyptian studies on MSI prevalence in CRC patients showed that it was higher than that reported from western population, yet there was no clear explanation for this difference.…”

Clinicopathological features of Egyptian colorectal cancer patients regarding somatic genetic mutations especially in KRAS gene and microsatellite instability status: a pilot study

“…However, MSI-H CRCs have been reported to demonstrate a more frequent association with proximal tumor location, poorly differentiated, mucin-containing histology, and advanced staging [23]. Another study revealed that proximal location (right side) was selected as predictors of MS-H CRC with p = 0.005 [24]. In our study, only three patients had a mass in the rectum, and they all had MS-H CRC and wild KRAS.…”

A new therapeutic approach for bone metastasis in colorectal cancer: intratumoral melittin

“…The low tumor cell viability was also demonstrated on gastric [ 37 ], lung cancer [ 49 ], esophagus [ 34 ], lymphoma [ 29 ], leukemia [ 27 ], ovarian cancer [ 28 ], breast cancer [ 48 , 50 ], cervical cancer [ 43 ], skin cancers [ 20 , 31 ]. Accordantly, the peptide effects on CRC cells have already been demonstrated [ 38 - 40 , 51 ].…”

“…Specifically, about metastases, melittin showed activity for lung [ 49 , 50 ], liver [ 28 , 51 ], and esophageal metastasis [ 34 ]. For bone CRC metastases, the present data are unprecedented.…”