ABSTRACT
A disproportionately large number of young (50 years); those from young black patients presented more often with a low methylation phenotype (CIMP-L) and high levels of microsatellite instability (MSI-H). Furthermore; as determined by real-time PCR using probe technology; the tissues from35of young blacks showed mutations within exon 1 of the KRAS gene. The BRAF-V600E mutation was only evident in the case of a single young black patient. Based on these results it seems likely that a proportion of CRC cases in young black patients from South Africa develop through the accumulation of mutations resulting in a mismatch repair deficiency linked to MSI-H and; possibly; germline mutations in the mismatch repair genes. The features in these patients are consistent with a diagnosis of the Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome. This finding has important implications for patient management and suggests that family members may be at high risk for CRC
Subject(s)
Black People , Colorectal Neoplasms , Young AdultABSTRACT
Background. Colorectal carcinoma (CRC) has a low incidence among the black African population. Largely unrecognised in the scientific literature is the fact that a disproportionately large number of young black patients (50 years old) present with CRC. Objectives. To analyse those tumours; which we propose may link them to morphological features associated with known genetic pathways. Methods. A retrospective review of South African patients histologically diagnosed as having CRC by the Division of Anatomical Pathology; National Health Laboratory Service (NHLS) and the University of the Witwatersrand (1 732 patients from 1990 to 2003). The histology was fully reviewed in 609 patients (1997 - 2002); and all specimens from patients 50 years of age were subjected to immunohistochemistry tests for mismatch repair proteins; as well as APC and p53 proteins. Results. Most young patients (50 years) were black (41v. 10white; p=0.001). Blacks had predominantly proximal tumours and significantly more poorly differentiated and/or mucinous tumours (p=0.006); and loss of mismatch repair protein expression was more evident than in whites. Conclusions. It seems likely that CRC in young blacks develops through the accumulation of mutations; most probably via mis- match repair deficiency or promoter methylation; which in turn is linked to poor differentia- tion and a mucinous architecture
Subject(s)
Black People , Colorectal Neoplasms , Young AdultABSTRACT
A 28 yr old Zulu presented with a painful swelling in the right hypochondrium and severe swelling of the legs of short duration. The serum alpha-fetoprotein concentration was over 2 X 10(5) ng/ml and imaging showed a large hepatic mass-lesion. Radionuclide venography revealed no flow through the inferior vena cava but flow through a large collateral vessel. Contrast venography showed the upper portion of the inferior vena cava to be occluded: large collateral vessels arose from the lower vena cava and the iliac veins. The histological features were those of longstanding hepatic venous outflow obstruction with irregular centrizonal and portal fibrosis: severe acute centrizonal congestion was not seen. This combination of findings indicates the presence of both membranous obstruction of the inferior vena cava, a rare developmental abnormality which predisposes to hepatocellular carcinoma formation, and invasion by the tumour of the inferior vena cava via the hepatic veins, an uncommon complication of hepatocellular carcinoma.