ALDH1A1 Expression in Colorectal Carcinoma: Immunohistochemical Evaluation and Correlation with Pathological Prognostic Factors

Abstract

Background: Colorectal cancer (CRC) is among the most prevalent cancers worldwide, marked by substantial biological variability. Aldehyde dehydrogenase 1A1 (ALDH1A1), which is a known cancer stem cell biomarker, has shown promise as a biomarker of aggressive cancer, although there is very little research done in South Asian populations.
Objectives: To study the IHC staining of ALDH1A1 in surgically removed CRC samples and its association with various pathological prognostic markers such as tumor grade, lymphovascular invasion (LVI), lymph node involvement, and AJCC pathological stage.
Materials and Methods: A prospective cross-sectional study was conducted over two years (March 2024–February 2026) at a tertiary academic centre. Fifty-five consecutively enrolled radical resection specimens of histopathologically confirmed CRC were assessed. ALDH1A1 IHC was performed using a primary mouse monoclonal antibody with heat-induced antigen retrieval. Expression was scored semi-quantitatively using a proportion score (0–3), intensity score (0–3), and composite H-score (0–300). Cases were classified as high (combined score 2–3) or low expression (combined score 0–1). Associations with clinicopathological variables were assessed using Fisher's exact test; receiver operating characteristic (ROC) examination was performed to determine the optimal H-score threshold.
Results: High ALDH1A1 expression was noticed in 43 of 55 cases (78.2%), with a mean H-score of 146.71 ± 82.01. Statistically significant associations were identified between high ALDH1A1 expression and lymphovascular invasion (90.3% vs. 62.5% in LVI-negative; p = 0.013), lymph node metastasis (86.2% vs. 69.2% in node-negative; p = 0.031), and advanced AJCC stage (p = 0.002). No significant association was observed with tumour site (p = 0.434) or tumour grade (p = 0.338), although poorly differentiated tumours showed the highest proportion of high expression (89.5%). ROC analysis demonstrated excellent discriminatory performance for H-score (AUC = 0.963; 95% CI 0.893–1.000; sensitivity 95.2%; specificity 92.3%; optimal cut-off ≥ 97.5).
Conclusion: Increased expression of ALDH1A1 represents an often observed and biologically relevant phenomenon in CRC that shows strong associations with markers of invasive/metastatic behavior. The H-score system for the immunohistochemical evaluation allows a reliable distinction of different expression patterns and could be included into the standard histopathological report.