Expression of p53 and CD31 in Malignant Salivary Gland Tumors: A Clinicopathological and Immunohistochemical Study

ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 55 Expression of p53 and CD31 in Malignant Salivary Gland Tumors: A Clinicopathological and Immunohistochemical Study Daniyar Anarbaevich Nishanov1, Otabek Bakhtiyorovich Abdurakhmonov2, Murod Sarvarovich Khudayorov2, Umidjon Abduganiyevich Soatov3 Republican Center of Pathological Anatomy¹; Termez Branch of Tashkent State Medical University3; Akfa Medline Clinic2 — Tashkent, Republic of Uzbekistan Tashkent State Medical University², Tashkent, Republic of Uzbekistan Abstract: Background: Salivary gland malignancies represent a diagnostically and therapeutically challenging group of head and neck tumors. Immunohistochemical biomarkers such as p53, CD31, VEGFR, and Ki-67 are essential in assessing the proliferative and angiogenic activity of these neoplasms. To evaluate the expression patterns of p53 and CD31 in malignant salivary gland tumors (MSCTs) and determine their diagnostic, prognostic, and clinical implications.Seventy patients diagnosed with MSCTs between 2017–2022 were analyzed. Immunohistochemical studies were conducted on 40 selected cases (20 mucoepidermoid carcinomas and 20 adenocarcinomas) using Bond Leica (Australia) processors with antibodies against p53, CD31, Ki-67, and VEGFR. Expressions were semi-quantitatively evaluated using the Allred scoring system.p53 expression in mucoepidermoid carcinoma was low in 70%, moderate in 20%, and high in 10% of cases, while adenocarcinomas showed low in 10%, moderate in 20%, and high in 70%. For CD31, 100% of mucoepidermoid tumors exhibited weak vascular density (10–15 vessels/field), whereas adenocarcinomas displayed strong vascularity (30–40 vessels/field). Adenocarcinomas of the salivary glands demonstrate significantly higher proliferative and angiogenic activity compared to mucoepidermoid carcinomas. p53 and CD31 can serve as reliable prognostic indicators for tumor aggressiveness and metastatic potential. Keywords: Salivary gland carcinoma, p53, CD31, angiogenesis, immunohistochemistry, prognosis, molecular pathology Introduction Salivary gland tumors (SGTs) are rare neoplasms accounting for 3–6% of all head and neck tumors. Despite their low incidence, these tumors pose significant diagnostic and therapeutic challenges due to their diverse histopathological spectrum. According to the World Health Organization (WHO, 2022), over 30 histological types of salivary gland tumors have been described. Malignant forms such as mucoepidermoid carcinoma, adenoid cystic carcinoma, and adenocarcinoma differ substantially in cellular morphology, proliferative activity, and metastatic potential. In recent years, the integration of molecular pathology and immunohistochemistry (IHC) has revolutionized salivary gland cancer diagnostics. Molecular biomarkers including p53, CD31, VEGFR, and Ki-67 are valuable tools for assessing proliferation, angiogenesis, and tumor aggressiveness. Understanding their expression profiles in malignant salivary tumors could enhance prognostic accuracy and guide individualized treatment strategies. Materials and Methods: This retrospective study was conducted at the Republican Oncology and Radiology Center, Tashkent, from 2017 to 2022. Seventy cases of malignant salivary gland tumors ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 56 were reviewed, and 40 representative cases (20 mucoepidermoid carcinomas and 20 adenocarcinomas) were subjected to IHC analysis. Sections of 4 μm were prepared and stained using antibodies for p53, CD31, Ki-67, and VEGFR. The Bond Leica (Australia) automated processor was used. Staining visualization was performed using DAB chromogen, and counterstaining was achieved with Mayer’s hematoxylin. The results were semi-quantitatively evaluated using the Allred scoring system (0–3) based on staining intensity and percentage of positive cells. p53 expression was predominantly low in mucoepidermoid carcinomas (70%), while adenocarcinomas showed high expression in 70% of cases. CD31 staining indicated strong vascular proliferation in adenocarcinomas compared to weak vascularization in mucoepidermoid carcinomas. Figure 1. p53 expression levels in mucoepidermoid vs. adenocarcinoma. Figure 2. CD31 vascular density comparison between tumor types. Discussion: The findings reveal a clear correlation between p53 overexpression and high CD31 vascular density in adenocarcinomas, suggesting enhanced proliferative and angiogenic potential within the tumor microenvironment. The p53 gene, a critical tumor suppressor, ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 57 normally regulates cell cycle arrest, DNA repair, and apoptosis. However, mutations in p53 lead to loss of these regulatory functions, resulting in uncontrolled cellular proliferation and resistance to programmed cell death. This loss of apoptotic control not only promotes tumor growth but also induces the secretion of angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), further stimulating neovascularization.On the other hand, CD31 (platelet endothelial cell adhesion molecule-1, PECAM-1) serves as a reliable immunohistochemical marker for microvessel density (MVD), reflecting the degree of tumor angiogenesis. Elevated CD31 expression in adenocarcinomas indicates an increased formation of new blood vessels, providing essential nutrients and oxygen to the growing neoplasm and facilitating the dissemination of malignant cells via hematogenous routes.The concurrent overexpression of p53 and increased CD31 density implies that p53 dysregulation may indirectly enhance angiogenic activity, establishing a microenvironment favorable for tumor invasion and distant metastasis. These results are consistent with prior studies by Speight et al. (2018) and Kawakita et al. (2019), who demonstrated that p53 abnormalities were associated with higher microvessel counts and poor differentiation grades in salivary gland carcinomas. Moreover, their investigations suggested that combined evaluation of p53 and angiogenic markers could serve as an important diagnostic and prognostic tool, aiding in the stratification of patients and guiding therapeutic decisions. Recent molecular analyses further support this interplay, highlighting that mutant p53 proteins can activate pro-angiogenic pathways through upregulation of HIF-1α and VEGF signaling, while CD31-positive endothelial proliferation is often seen at the invasive fronts of aggressive tumors. Therefore, assessing the expression profiles of both p53 and CD31 not only provides insight into the biological behavior of adenocarcinomas but also offers potential targets for anti-angiogenic and molecular-based therapies aimed at improving clinical outcomes. Incorporating IHCbased molecular profiling into routine histopathological diagnostics significantly enhances the accuracy of tumor classification and reduces the risk of diagnostic discrepancies, particularly in morphologically overlapping carcinoma subtypes. By combining conventional morphology with immunophenotypic and molecular markers—such as p53, Ki-67, CD31, HER2/neu, and EGFR—clinicians are able to obtain a more comprehensive understanding of tumor biology, leading to more personalized and effective therapeutic approaches.The mean diagnostic cost per patient, estimated at approximately 3,333,000 UZS, demonstrated a favorable cost-benefit ratio when compared with the long-term economic and clinical outcomes. Although the initial expenditure for IHC and molecular testing may appear substantial, it translates into substantial economic advantages by minimizing unnecessary treatments, reducing recurrence rates, and improving overall survival. Early molecular stratification allows the selection of targeted therapies, resulting in shorter hospital stays, fewer complications, and optimized use of healthcare resources. Furthermore, implementation of such profiling in tertiary oncology centers has shown to enhance prognostic accuracy, especially in tumors with complex histogenesis such as salivary gland, colorectal, and hepatocellular carcinomas. Studies have indicated that patients whose treatment plans were guided by IHC and molecular markers exhibited a 20–30% improvement in 3-year disease-free survival compared to those managed with conventional histology ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 58 alone.Beyond its diagnostic and prognostic value, IHC-based molecular profiling also facilitates tumor behavior prediction, identification of therapy-resistant clones, and monitoring of treatment response dynamics. For example, overexpression of mutant p53 combined with high CD31 vascular density may indicate an aggressive phenotype with enhanced metastatic potential, warranting intensified follow-up and adjuvant therapy.Overall, integrating molecular immunohistochemistry into standard oncologic protocols represents a pivotal step toward precision oncology in Uzbekistan. It ensures that therapeutic strategies are not only morphologically justified but also molecularly tailored, improving both patient outcomes and the economic sustainability of cancer care systems. Conclusion 1. Adenocarcinomas of the salivary glands exhibit higher expression of p53 and CD31 than mucoepidermoid carcinomas. 2. Combined immunohistochemical evaluation of p53 and CD31 serves as a reliable prognostic tool for tumor aggressiveness. 3. Integration of these biomarkers into diagnostic protocols can enhance personalized management of malignant salivary gland tumors. Practical Recommendations It is recommended to include p53 and CD31 evaluation in the diagnostic panel for all malignant salivary gland tumors. Development of regional IHC laboratories across Uzbekistan would promote early detection and improve patient outcomes. References 1. Speight, P. M., Farthing, P. M., & Barnes, L. (2018). Salivary gland tumours in the WHO classification: A critical review. Pathology, 50(6), 569–577. 2. Rajasekaran, K., et al. (2021). Salivary gland tumors: Current concepts and new developments. Otolaryngologic Clinics of North America, 54(3), 437–450. 3. Seethala, R. R., & Stenman, G. (2022). Update from the 2022 WHO classification of head and neck tumors: Salivary neoplasms. Head and Neck Pathology, 16(1), 40–53. 4. Kawakita, D., et al. (2019). Prognostic impact of VEGF and Ki-67 expression in salivary gland cancers. Oral Oncology, 94, 50–57. 5. Nishanov, D. A., Abdurahmonov, O. B., Khudayorov, M. S., & Soatov, U. A. (2024). Salivary gland malignancies in Uzbekistan: Immunophenotypic evaluation and clinical relevance. Uzbekistan Medical Journal, 5(2), 45–52.