Serrated epithelial change (SEC) remains a complex histological finding in patients with inflammatory bowel disease (IBD). Clinicians often encounter these hyperplastic-like mucosal changes during routine surveillance colonoscopies. However, the exact role of p53 staining in SEC as a predictor of malignancy remains under significant debate. Recent evidence suggests that while some SEC cases harbor molecular abnormalities, the majority do not progress directly to colorectal neoplasia. Consequently, identifying reliable biomarkers for risk stratification is essential for improving patient outcomes.

A recent study analyzed p53 immunohistochemistry across three distinct patient cohorts to clarify this relationship. The researchers examined 112 SEC biopsies from IBD patients both with and without a history of colorectal neoplasia. Additionally, they included a control group of IBD patients lacking SEC entirely. They graded nuclear staining intensity and extent to identify aberrant patterns indicative of mutation. Furthermore, the study meticulously reviewed every stained slide to ensure the absolute absence of morphological dysplasia within the SEC samples. This rigorous approach provided clear insights into the molecular landscape of these controversial lesions.

Diagnostic Reliability of p53 Staining in SEC

The study results revealed that aberrant p53 staining is remarkably uncommon in SEC. Even in patients with a history of synchronous or metachronous dysplasia, the SEC biopsies rarely showed overexpression or complete loss of p53 protein. Therefore, this specific biomarker may have limited utility in differentiating high-risk SEC from reactive inflammatory changes. Moreover, the lack of aberrant staining suggests that SEC might not always follow the traditional p53-driven carcinogenesis pathway seen in colitis-associated cancer. Instead, alternative molecular mechanisms likely contribute to the increased neoplasia risk observed in some SEC patients.

In conclusion, although SEC is associated with a higher risk of neoplasia in certain clinical contexts, p53 immunohistochemistry does not reliably highlight these risks. Clinicians should continue to rely on comprehensive endoscopic surveillance and established histological criteria for management. Therefore, further research into other genetic markers is necessary to refine our clinical approach. This will help optimize surveillance protocols for the growing population of IBD patients in India and across the globe.

What is Serrated Epithelial Change (SEC)?

SEC refers to hyperplastic polyp-like mucosal changes found in IBD patients that do not show typical morphological signs of dysplasia. It is often detected in random or non-targeted colon biopsies during surveillance.

Does p53 staining help predict cancer risk in SEC?

Current research indicates that aberrant p53 staining is rare in SEC. Consequently, it is not currently considered a highly sensitive tool for predicting synchronous or metachronous colorectal neoplasia in these specific lesions.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a professional recommendation. Refer to the latest local and national guidelines for clinical practice.

References

1. Bahceci D et al. Aberrant p53 immunohistochemical staining is uncommon in serrated epithelial change, regardless of association with dysplasia. Histopathology. 2026 Apr 23. doi: 10.1111/his.70159. PMID: 42023487.


2. Singhi AD et al. Targeted next-generation sequencing supports serrated epithelial change as an early precursor to inflammatory bowel disease-associated colorectal neoplasia. Hum Pathol. 2021;112:9-19. doi: 10.1016/j.humpath.2021.03.002.