Abstract B07: Molecular characterization of colorectal cancer in West Africans

Introduction: To reduce global disparities in cancer outcomes, there is a need for more concerted efforts to develop the capacity of health care providers to appropriately diagnose and treat common cancers. Colorectal cancer (CRC) incidence in indigenous Africans is significantly lower than in Caucasians but there is a paucity of data on the genetic determinants and molecular biology of colorectal cancer in Nigerians. Lynch syndrome (LS), defined by germ-line mutation in one of the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2), is the most common heritable syndrome predisposing to CRC. Loss of MMR proteins can be readily detected by immunohistochemistry (IHC) in both Lynch syndrome and sporadic CRC, and further testing for mutated BRAF protein is helpful in distinguishing Lynch syndrome from sporadic CRC. Materials and Methods: With IRB approval and under a collaborative arrangement with the University of Chicago, seven tissue microarray (TMA) blocks were constructed from CRC samples obtained from the University College Hospital in Ibadan, Federal Teaching Hospital in Gombe, Olabisi Onabanjo University in Sagamu and Ahmadu Bello University in Zaria. TMAs included duplicate 1.0-mm cores of CRC tissue and adjacent normal. For the four MMR proteins, IHC was performed on these TMAs with the following antibodies: MLH1 (Thermo Scientific Pierce Biotech), MSH2 (Life Technologies), MSH6 (Novex), PMS2 (Pierce), anti-BRAF V600E (Roche). All IHC-stained slides (MLH1, MSH2, MSH6, PMS2) were evaluated for expression levels of those proteins in the tumor tissue relative to normal tissue (control) using the following scoring criteria: normal expression was defined as nuclear staining within tumor cells, negative protein expression was defined as complete absence of nuclear staining within tumor cells, and cases with immunoreactivity in 0-10% of tumor cells were scored as equivocal. The slides stained with anti-BRAF V600E (VE1) were scored on a scale of 0 to 3. Strong cytoplasmic staining was scored as 3, medium as 2, 1 as weak, and 0 when the staining was absent. Results: Of the total evaluable CRC cases, 152 of 293 (52%) were males aged between 16 and 90 years, mean age of 47.33 +/-17.57, while there were 141 female cases, with a mean age of 49.71+/-14.75. More than a quarter of the cases were under 40 years of age. By our IHC screening algorithm, 140 (48%) of the patients had intact MMR proteins, while 153 (52%) patients had at least one MMR protein absent.