Department of Gastroenterology, Vrije Universiteit Amsterdam, The Netherlands.
MRC Human Genetics Research Unit, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town and Affiliated Hospitals, South Africa.
S Afr J Surg. 2022 Mar;60(1):28-33.
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 of MMR deficiency in an indigenous African population.
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.
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% ( = 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.
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.
南非本土非洲人群的结直肠癌（CRC）发病率较低（男性标准化发病率为 11.29/10 万，女性为 7.27/10 万），且发病年龄较早。林奇综合征（LS）是一种遗传性错配修复（MMR）基因异常，占高发地区新诊断 CRC 的 3-4%。有证据表明，在低发地区，MMR 异常对总体 CRC 负担的贡献可能会增加。我们旨在确定 MMR 缺陷在本土非洲人群中的流行率。
从临床和病理记录中确定了 66 名自报的、诊断时年龄小于 50 岁的本土非洲 CRC 患者队列。对原始组织病理学进行了回顾性分析，以确认诊断并确定提示 MMR 异常的特征（推进边缘、黏液性、淋巴细胞浸润、克罗恩样反应）。在有足够组织的情况下，对样本进行切片并染色以检测四种 MMR 蛋白。
组织病理学检查证实 31 例为腺癌。在这些标本中，至少有一个特征提示存在 MMR 异常。27 例使用标准免疫组织化学（IHC）对所有四个 MMR 蛋白进行染色。发现 37%（=27/66）的病例存在 MMR 缺陷。在 MMR 功能正常的组中，诊断的中位年龄为 35 岁，而在 MMR 缺陷的组中为 44 岁，<0.008。两组之间没有观察到其他显著差异。
在该队列中年龄较大的患者的结直肠癌细胞中，MMR 缺陷很常见，但非常年轻的本土非洲 CRC 似乎并非由错配修复基因突变引起。
