EXPRESSION OF CLASPIN IN SQUAMOUS CELL CARCINOMA OF CERVIX AND ITS ASSOCIATION WITH P16 EXPRESSION AND CLINICOPATHOLOGIC PARAMETERS

Abstract

Background: Cervical cancer is a preventable gynecological malignancy, yet it remains a significant health burden in developing countries. While screening and vaccination must be our primary objective to fight against cervical cancer, the ground reality that the diagnosis is still made most frequently at an advanced stage cannot be forgotten. Hence biomarkers identified in cervical cancer has significance in understanding the prognosis and reducing cervical cancer related deaths. Claspin is a protein with key role in checkpoint signaling, genome duplication and consecutively increased replication. Elevated levels of Claspin have been seen in multiple solid tumors. Aim of the study: To associate of Claspin expression with clinicopathological parameters and P16 expression in Squamous Cell Carcinoma (SCC) of Cervix. Methods: The study was conducted in Department of Pathology in Collaboration with Department of Obstetrics and Gynecology (OBG), Sri Devaraj Urs Medical College attached to R.L.Jalappa Hospital and Research center, Tamaka, Kolar during the period of July 2022 to December 2023.The study included 80 cases of primary diagnosis of SCC cervix along with 10 cases of High grade squamous intraepithelial lesion (HSIL) and 10 cases of cervical tissue with normal histological features. Immunohistochemistry (IHC) was performed using antibodies against P16 and Claspin. Expression of Claspin and P16 was analyzed and interpreted. Claspin expression was associated with P16 and xvi clinicopathological parameters of carcinoma cervix. Statistical analysis was performed using Chi-square test. A p value of less than 0.05 was considered substantially significant. Results: The average age of cervical carcinoma diagnosis in this study was 55 years, with a significant majority (73.75%) being post-menopausal. All of the subjects had symptomatic presentation, most commonly bleeding per vagina (52.5%) and on per speculum examination 70% cases had an ulceroproliferative growth. On radiological examination majority of the cases had tumor size more than 4cm (68.5%) but lymph node involvement was seen in only (31.5%) cases. Maximum number of cases were diagnosed in Stage III highlighting the late presentation of the rural population in India. On histopathological examination most cases were well- differentiated (63.75%) and TILs were seen markedly increased in 56.92% cases. The study also found block positivity for P16 in 83.75% of cases, indicating HPV-associated SCC. Claspin is a potential biomarker, highly expressed in SCC cervix (88.75%, p<0.005), significantly higher than HSIL (50%) and normal tissue (0%). Increased Claspin expression was linked to P16 positivity but was not statistically significant. Neither Claspin nor P16 showed any significant association with the various clinicopathological parameters such as age, postmenopausal status, parity, clinical findings, lymph node status, size of tumor, stage, grade and TILs. Conclusion: Claspin is a potential biomarker for cervical cancer, particularly in HPV-associated cases. This study has shown the increased expression of Claspin and P16 in cervical cancer. xvii Drugs targeting Claspin has the potential to increase sensitivity to chemotherapeutic drugs like Cisplatin. Further research is needed to explore its prognostic significance and relationship with clinicopathological parameters. This study contributes to the ongoing quest for effective biomarkers, ultimately aiming to improve patient outcomes and reduce mortality rates in cervical cancer.