Significance of MFAP5, IMP3 and Desmin Expression as Diagnostic Biomarkers for Colorectal Cancers in Biopsy Specimens

Background: Diagnosis of invasive colorectal cancer is challenging, especially when evaluated in biopsy specimens. Submucosal invasion and desmoplastic stroma are important in this regard but may not be constantly present. Current biomarkers, including smooth muscle actin and desmin, lack sufficient sensitivity and specificity. Microfibril-associated protein 5 (MFAP5) and insulin-like growth factor II mRNA-binding protein 3 (IMP3) may be useful as biomarkers for invasion. This study evaluated their diagnostic utility along with desmin in invasive colorectal cancer detection. Methods: Seventy-seven colonic specimens were divided into four groups: normal mucosa, adenomatous polyps with low-grade dysplasia, high-grade dysplasia/intramucosal carcinoma, and invasive carcinoma. Immunohistochemical expression for MFAP5, IMP3, and desmin was conducted. Results: Among the studied groups, a significant reduction "complete loss" of stromal MFAP5 expression was observed in adenomatous polyps with high-grade dysplasia/intramucosal carcinoma and invasive carcinoma groups, p < 0.001. A nearly significant overexpression (moderate to strong) of epithelial MFAP5 expression was noted in the two groups, p = 0.08. IMP3 was preferentially expressed in invasive carcinoma, p < 0.001. Desmin expression showed no significant differences between the studied groups. Combined use of MFAP5 (stromal) and IMP3 achieved 91% sensitivity and 96% specificity for invasive carcinoma detection. Conclusion: The integration of MFAP5 and IMP3 biomarkers in detecting invasive colorectal cancer can have valuable role in certain clinical contexts by reducing interobserver variability typically seen with H&E evaluation and enabling judging in situations as specimens with prominent stroma or pseudoinvasion. Complete stromal MFAP5 loss can be a promising indicator for detecting altered tumor-associated stroma.