SIGNIFICANCE OF EXPRESSION OF EPITHELIAL MESENCHYMAL TRANSITION MARKERS IN SQUAMOUS CELL NEOPLASMS OF UTERINE CERVIX – A LABORATORY OBSERVATIONAL STUDY

Abstract

Cervical cancer is the fourth most common cause of cancer in women worldwide. Cervical cancer is a major health problem worldwide with developing countries like India contribute maximum to the global burden. Epithelial Mesenchymal Transition is a phenomenon related to carcinogenesis which is characterize by morphological change in neoplastic epithelial cells to mesenchymal cells. This eventually leads to increase motility, increase invasiveness in neoplastic cells. Cytokeratin 19 is a basal cell marker, Vimentin is a cytoskeletal protein while RhoC contributes to reorganization of cytoskeletal. RhoC has also role in targeted therapy for different cancers. Objectives :- 1. To observe expression of the 3 epithelial mesenchymal transition markers (cytokeratin 19, vimentin and RhoC) in normal, HSIL and squamous cell carcinoma. 2. To correlate expression of the 3 epithelial mesenchymal transition markers (cytokeratin 19, vimentin and RhoC) among normal, HSIL, squamous cell carcinoma and histological grade and clinical/radiological stage of the disease. Materials and Methods :- Seventy cases are taken. Out of 70, 10 cases were of normal cervix, 30 cases were of HSIL and 30 cases of newly diagnosed squamous cell carcinoma of cervix. Cinicopathological findings like age, parity, chief complaint, per vaginal, per speculum findings, grading and FIGO staging were obtained. Immunohistochemistry was performed for 3 markers :- Cytokeratin 19, Vimentin and RhoC. Correlation between expressions of Cytokeratin 19, Vimentin and RhoC with the study groups are analyzed. A p value of <0.005 was considered statistically significance. Results :- Mean age ± Standard deviation among normal, HSIL and SCC groups were 46.2 ± 16.12 years, 49.10 ± 10.13 years and 56.27 ± 9.29 years respectively. This difference of mean age across normal, HSIL and SCC was statistically significant. A weak basal cell positivity was seen in 80% cases with normal cervix. 93.3% and 100% cases of HSIL and SCC were positive for the expression of CK19. This difference of expressions of CK19 among HSIL and SCC of cervix was statistically insignificance (Fischer’s exact test, p value=0.492). All the cases of normal cervix was negative for Vimentin expression. 33.3% and 73.3% cases of HSIL and SCC respectively showed positive vimentin expression. This difference of expressions of Vimentin across normal, HSIL and SCC was statistically significant (χ2 = 19.496, p <0.001). 10%, 20% and 83.33% cases of normal cervix, HSIL and SCC showed positive expressions for RhoC respectively. This difference in the expressions of RhoC across normal, HSIL and SCC was statistically significant (χ2 = 30.241, p <0.001). No statistically significant difference between expressions of vimentin and RhoC and Histopathological grade (χ2 = 1.327, p = 0.515 and χ2 = 2.030 , p = 0.362 respectively) and the expressions of Vimentin and RhoC and FIGO staging were noted (χ2 = 0.292 , p = 0.589 and χ2 = 0.055, p = 0.815 respectively). Comparison between expression of CK19 and Histopathological grade and FIGO staging was not possible because all the cases of CK19 were positive for CK19 expression. Conclusion :- Epithelial mesenchymal transition is an important phenomenon that promotes invasion, migration in cervical cancer. Increase expression of CK 19 in HSIL and SCC of cervix highlights role of basal cells of cervix in cervical carcinogenesis.Vimentin and RhoC in cervical cancer promotes the phenomenon of epithelial mesenchymal transition and eventually leads to malignant transformation, increase motility and increase invasiveness. Further multicentric studies with a larger sample size are required. Further studies on role of RhoC in targeted therapy for cervical cancer is recommended.