Immunohistochemical determination of mismatch repair gene product in colorectal carcinomas in a young indigenous African cohort

Keywords: inherited colorectal cancer, mismatch repair status

Abstract

Background: Colorectal cancer (CRC) in the indigenous African population of South Africa is uncommon (age standardised incidence rates of 11.29 for males and 7.27/100 000 for females) and tends to occur at a young age. Lynch syndrome (LS), an inherited mismatch repair (MMR) gene abnormality, accounts for 3–4% of newly diagnosed CRCs in high incidence areas. There is some evidence that the contribution of an MMR abnormality to the overall CRC burden may be increased in low incidence areas. We aimed to determine the prevalence o MMR deficiency in an indigenous African population.

Methods: A cohort of 66 self-declared indigenous African patients, less than 50 years of age at diagnosis with CRC was identified from clinical and pathological records. The original histopathology was reviewed to confirm the diagnosis and features suggestive of MMR abnormality determined (pushing edge, mucinous, lymphocytic infiltration, Crohn’s like reaction). Where sufficient tissue was available, samples were sectioned and stained for the four MMR proteins.

Results: Histopathological examination confirmed adenocarcinoma in 31 individuals. At least one feature suggestive of MMR was identified in 22 of these specimens. Twenty-seven cases were stained for all four MMR proteins using standard immunohistochemistry (IHC). MMR deficiency was found in 37% (n = 10/27) of cases. Median age of diagnosis was 35 years in the MMR-proficient group and 44 years in the MMR-deficient group, < 0.008. No other significant differences between the groups were noted.

Conclusion: MMR deficiency was common in colorectal carcinomas in the older patients in this cohort, but very young indigenous Africans CRCs do not appear to result from mismatch repair gene mutations.

Author Biographies

R Holla, Vrije Universiteit Amsterdam

Department of Gastroenterology, Vrije Universiteit Amsterdam, The Netherlands

A Vorster, University of Cape Town

MRC Human Genetics Research Unit, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town and Affiliated Hospitals, South Africa

M Locketz, University of Cape Town

Division of Anatomical Pathology, National Health Laboratory Service and the University of Cape Town, South Africa

M De Haas, University of Cape Town

MRC Human Genetics Research Unit, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town and Affiliated Hospitals, South Africa

O A Oke, University of Cape Town

Colorectal Surgery Unit, Groote Schuur Hospital, University of Cape Town, South Africa

D Govender, University of Cape Town

Division of Anatomical Pathology, National Health Laboratory Service and the University of Cape Town, South Africa

R Ramesar, University of Cape Town

MRC Human Genetics Research Unit, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town and Affiliated Hospitals, South Africa

P A Goldberg, University of Cape Town

Colorectal Surgery Unit, Groote Schuur Hospital, University of Cape Town, South Africa

Published
2022-04-11
How to Cite
Holla, R., Vorster, A., Locketz, M., De Haas, M., Oke, O., Govender, D., Ramesar, R., & Goldberg, P. (2022). Immunohistochemical determination of mismatch repair gene product in colorectal carcinomas in a young indigenous African cohort. South African Journal of Surgery, 60(1), 28-33. Retrieved from http://sajs.redbricklibrary.com/index.php/sajs/article/view/3687
Section
Colorectal Cancer