Immunohistochemical Expression of MSH2 and MLH1 and Their Correlation with Histological Grades of Colorectal Carcinoma at Uganda Cancer Institute

Colorectal cancer, a disease that affects the large intestine, is a growing health challenge in Uganda. Like many cancers, it often begins as a small, harmless growth that slowly changes over years into something dangerous. Inside our cells, a sophisticated maintenance crew works constantly to fix mistakes in our genetic code, the instruction manual that tells cells how to behave. When this repair system fails, errors pile up, and cells can grow out of control. Two specific proteins, known as MSH2 and MLH1, act as the foremen for this repair crew. If these proteins are missing or broken, the cell loses its ability to fix genetic damage, which can lead to cancer. Doctors use a technique called immunohistochemistry to look for these proteins in tissue samples. By staining the cells, they can see if the foremen are present and doing their job, or if they have vanished, leaving the genetic code vulnerable. Understanding whether these proteins are present in Ugandan patients is crucial because it helps doctors determine the nature of the cancer and decide on the best path for treatment.

In a recent study at the Uganda Cancer Institute, researchers set out to examine how often these repair proteins are missing in patients with colorectal cancer. They looked back at 41 tissue samples collected over six years from patients who had been diagnosed with the disease. Using the staining technique mentioned earlier, the team carefully checked each sample to see if the MSH2 and MLH1 proteins were visible. They also noted how the cancer cells looked under a microscope, categorizing them as well-differentiated, meaning they still looked somewhat like normal cells, or poorly differentiated, meaning they looked very disorganized and aggressive. The goal was to see if the absence of these repair proteins was linked to how aggressive the tumors appeared.

The results revealed that in the vast majority of cases, the repair crew was still intact. The MSH2 protein was found in 95 percent of the tissue blocks, and the MLH1 protein was present in 92.7 percent. This means that in most of the patients studied, the specific genetic repair system involving these two proteins was not broken. Only a small fraction of cases showed a complete loss of these proteins, with MSH2 missing in about 5 percent of samples and MLH1 missing in roughly 7 percent. The researchers also found that most of the tumors were well-differentiated, followed by moderately and poorly differentiated types. When they compared the presence of the proteins to the type of tumor, they found no clear link between the MSH2 protein and how the cancer cells looked. However, they did notice a connection with the MLH1 protein. The absence of MLH1 appeared to be associated with tumors that were poorly differentiated, suggesting that when this specific protein is missing, the cancer cells tend to look more disorganized.

These findings suggest that for most colorectal cancer patients in this specific group, the loss of these two repair proteins is not the main driver of the disease. While the study confirms that immunohistochemistry is a practical and cost-effective way to screen for these defects, it also highlights that this method alone does not tell the whole story. The researchers noted that because the sample size was relatively small and the study looked back at old records, they could not draw definitive conclusions about cause and effect. They recommend that future studies include more detailed genetic testing to fully understand the molecular causes of cancer in Uganda. For now, the work provides a solid foundation, showing that while these repair proteins are usually present, checking for their absence remains a valuable step in understanding the disease and guiding care in a resource-limited setting.