Noza Hilbertina1, Nurjati Chairani Siregar2, Murdani Abdullah3, Septelia Inawati Wanandi4
1Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta; Department of Anatomic Pathology, Faculty Medicine, Universitas Andalas, Padang, Indonesia.
2Department of Anatomic Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
3Department of Internal Medicine, Division of Gastroenterology, Faculty Medicine, Universitas Indonesia, Jakarta, Indonesia.
4Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Objective: Tumor microenvironments consisting of stroma and extracellular matrix play important roles in tumor progression, particularly through the induction of epithelial-mesenchymal transition (EMT). It has been suggested that the phenotype of cancer-associated fibroblasts (CAFs) in stroma might be correlated with the prognosis of patients with colorectal carcinoma (CRC). We aimed to determine the stromal and CAF types for prognostic determinants of CRCs associated with tumor budding (TB) grade, reflecting EMT. Materials and Methods: Using hematoxylin and eosin-stained paraffin wax sections from 23 patients with CRC, three stromal and two CAF phenotypes were evaluated, TB grades, invasion depth, lymph node metastases, and lymphovascular invasion (LVI) were also analyzed as established prognostic determinants. Data were analyzed statistically using the Chi-squared tests. Results: There was a significant association between CAF phenotype and TB grade (P < 0.01). CRC specimens with immature CAF have higher TB grades than the mature phenotype. Nevertheless, a significant association between stroma and TB grade could not be demonstrated. Moreover, high TB grades were significantly associated with lymph node metastasis (P < 0.01) and LVI (P < 0.01). However, there were no significant associations between CAF phenotype and either of these prognostic determinants. Conclusion: CAF phenotype could be considered as a prognostic determinant of CRC through its association with TB grade, indicating the role of CAFs in EMT processes. Future studies are required to examine the secretomes of CAFs that play important roles in EMT and determine the prognosis for patients with CRCs.
Keywords: Cancer-associated fibroblasts, prognostic determinants, stromal phenotype, tumor budding.