Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients

Abstract

Colorectal carcinoma is uncommon in Egypt, but a high proportion of cases occurs before age 40 years and in the rectum. We compared the molecular pathology of 59 representative Egyptian patients aged 10-72 to Western patients with sporadic, young-onset, or hereditary non-polyposis colorectal cancer syndrome (HNPCC)-associated carcinoma and found significant differences. Most Egyptian cancers were rectal (51%) and poorly differentiated (58%). High levels of microsatellite instability (MSI-H) were frequent (37%) and attributable in some cases (36%) to methylation of the promoter of the hMLH1 mismatch repair gene, but no MSI-H cancer had loss of hMSH2 mismatch repair gene product of the type seen with germline hMSH2 mutation in HNPCC. K-ras mutation was uncommon (11%). In subset analyses, high frequencies of MSI-H in rectal carcinomas (36%) and p53 gene product overexpression in MSI-H cancers (50%) were found. MSI-H and K-ras mutation in Egyptians under age 40 were unusual (17% and 0%, respectively), and schistosomiasis was associated with MSI and K-ras mutation. Cluster analysis identified 2 groups: predominantly young men with poorly differentiated mucinous and signet-ring cell colorectal carcinoma lacking K-ras mutation; older patients who had well- or moderately differentiated adenocarcinoma often with MSI-H, K-ras mutation and schistosomiasis. Our findings show that the molecular pathology of colorectal cancer in older as well as younger Egyptians has unique differences from Western patients, and schistosomiasis influences the molecular pathogenesis of some tumours.

Clinicopathological patterns and challenges of management of colorectal cancer in a resource-limited setting: a Tanzanian experience

“…However, despite this variation, the molecular characteristics remain similar throughout the world [5,6]. While recent studies have shown that the incidence of colorectal cancer is increasing in sub-Saharan Africa, especially in the urban centers [7,8], the converse is true in the developed world where the incidence of colorectal cancer is declining with a relatively good outcome of treatment attributable to early detection, especially in high-risk individuals due to widespread screening of the susceptible population, early presentation, and advances in diagnostic tools and treatment modalities [9]. …”

Mutations in codons 12 and 13 of K-ras exon 2 in colorectal tumors of Saudi Arabian patients: frequency, clincopathological associations, and clinical outcomes

“…Previous studies from the Middle East (or in the Arab population) that enrolled a relatively large number of patients and included patients with different stages of the disease, reported K-ras mutation rates of 28-56% in Saudi Arabia (Abubaker et al, 2009;Zahrani et al, 2014;Beg et al, 2015;Dallol et al, 2016), 33-45% in Turkey (Gumus et al, 2013;Baskin et al, 2014), and 33-44% in Jordan (Elbjeirami and Sughayer, 2012;Gumus et al, 2013). Lower mutation rates were observed in countries to the west of Saudi Arabia, such as Egypt (11-18%) (Soliman et al, 2001;Gumus et al, 2013), and Morocco (24%) (Marchoudi et al, 2013). To our knowledge, our study includes the second largest number of patients with metastatic disease, after 1,106 patients enrolled in one study in Turkey (Gumus et al, 2013).…”

“…These trials recruited patients mostly from western countries, with a K-ras mutation rate of about 40-45% (Douillard et al, 2010;Ibrahim et al, 2010;Peeters et al, 2010). Evidence suggests that the molecular pathology of CRC in the Middle Eastern patients is different than that of patients from the western world (Soliman et al, 2001). A difference in the prevalence of K-ras mutations in mCRC has also been described according to the geographic area of residence, with a higher prevalence found in western Europe compared to areas outside Europe (Van Cutsem et al, 2011).…”

Detection of K-ras gene mutation by polymerase chain reaction/restriction fragment length polymorphism in Egyptian patients with colorectal cancer

“…However, a much lower incidence of the K-ras gene mutation (11%) among Egyptian CRC patients (n = 59) was recorded by Soliman et al (2001). The difference in incidence may be related to two main factors.…”

“…Soliman et al (2001) showed that Egyptian CRC patients (n = 59) were relatively younger than their Western counterparts (44%, <40 years), male to female ratio of 1.36, about half of the tumors were located in the rectum (51%), and 37% of the tumors were mucinous. Soliman et al (2001) showed that Egyptian CRC patients (n = 59) were relatively younger than their Western counterparts (44%, <40 years), male to female ratio of 1.36, about half of the tumors were located in the rectum (51%), and 37% of the tumors were mucinous.…”