Our study aimed to examine the association between CD103 and E-cadherin immunoexpression and pelvic LN metastasis in cervical SCC. The demographic characteristics align with the existing understanding of cervical SCC patients who undergo surgery. These patients are typically in the age group of 40–50 years old, present with early-stage disease, exhibit a non-keratinizing SCC histopathological subtype, have moderate differentiation, and possess a tumor size of less than 4 cm.4,18–21
This study found a significant association between CD103 immunoexpression and pelvic LN metastasis in cervical SCC. It was observed that as the immunoexpression of CD103 decreased, the ability of tumor cells to metastasize to pelvic LNs increased. Furthermore, a decrease in CD103 expression was found to be linked to a decrease in CD8 + T cell cytotoxic function. These findings are consistent with a previous study conducted by Koh et al., which also reported that lower intratumoral CD103 + was associated with LN metastasis in pulmonary SCC.22 However, our results contradict those of the study conducted by Lai et al, which found that elevated CD103 + immunoexpression was associated with a reduced time to metastasis in cutaneous SCC.18
CD103 is an integrin present at the cell surface of both innate and adaptive immune cells.23 One important type of cell that expresses C
CD103 is CD8 + TRM, which plays a critical role in fighting cancer.10 Previous studies have shown that CD8 + TIL are associated with improved prognosis in various solid tumors.24–26 CD103 can bind to E-cadherin and enhance the cytotoxic function of CD8 + TRM against tumor cells. The impact of CD103 immunoexpression on tumor prognosis has also been studied in various malignancies. A study by Komdeur et al found that high expression of CD103 was strongly associated with improved prognosis in CC.27 Similarly, Chu et al reported that a higher density of CD103 + TIL is associated with longer overall survival and disease-free survival in esophageal SCC, suggesting that it may be a promising prognostic marker.28
Our study also examined the relationship between E-cadherin immunoexpression and pelvic LN metastasis in cervical SCC. However, we found no significant correlation between the two. This result aligns with the findings of Webb et al., who found that CD103 + TIL was associated with high-grade serous ovarian carcinoma survival, while E-cadherin expression was not associated with CD103 + TIL.15 In contrast, our result differs from that of Jiang et al., who discovered that the expression levels of E-cadherin were significantly lower in patients with early-stage SCC with intravascular tumor thrombus and LN metastasis compared to patients with SCC but without tumor thrombus or LN metastasis.29
E-cadherin is an adhesion molecule required for normal cell to adhesion and helps maintain tissue integrity and homeostasis. This integrin has associated with cancer metastasis and can be a progressive marker in tumor invasion. Based on morphological and molecular genetic parameters, there are currently two known patterns of invasive growth, collective invasion and individual invasion. These two are a great extent determined by the tumor environment and the molecular changes within tumor cells. Collective invasion is characterized by the migration of tumor cells in groups, whereas individual invasion pertains to migration of single individual tumor cell. In the collective invasion type, group of cells that are interconnected by cadherins and intercellular gap junction migrate as a whole.29,30
The transition from individual to collective migration is crucial for increasing the invasiveness of the tumor. This transition can be achieved through two pathways: EMT (epithelial-mesenchymal transition) and CAT (collective-amoeboid transition). During EMT, there is a decrease in E-cadherin expression, which causes malignant tumor cells to lose intracellular contacts. This enables them to invade and penetrate the surrounding stromal matrix, initiating active migration. A collective-amoeboid transition occurs when the tumor mass, which initially invades surrounding tissues as collective multicellular groups, dissociates into single migrating cells that move using an amoeboid mechanism. Therefore, in the CAT pathway, E-cadherin and integrin expression remain highly expressed.30–33
The invasion pattern theory mentioned above confirms the findings of this study. Our study found no significant link between E-cadherin expression and LN metastasis in cervical SCC. In this study, within the group of cervical SCC cases with LN metastasis, 35% showed high E-cadherin immunoexpression. This suggests that these tumor cells maintained intercellular adhesion and invaded the pelvic LNs collectively through the CAT pathway.30–33
Furthermore, E-cadherin is the only known ligand for CD103 in epithelial cell surface molecules.15 The binding of CD103 to E-cadherin enhances the anti-tumor activity of CD8 + T cells.10 The fact that our study discovered a significant association between pelvic LN metastasis and decreased CD103 expression, but not with decreased E-cadherin expression, may indicate that factors other than E-cadherin expression determine CD103 + CD8 + T lymphocyte infiltration.