IMMUNOHISTOCHEMICAL EXPRESSION OF MDM2 IN INVASIVE DUCTAL CARCINOMA OF BREAST AND ITS ASSOCIATION WITH HISTOPATHOLOGICAL PARAMETERS AND HORMONAL STATUS

Abstract

BACKGROUND: Worldwide, breast cancer ranks first with regards to incidence as well as mortality rates among females. Out of all the breast cancer types, ductal carcinoma is by far the most prevalent one. MDM2 exerts a key negative control on p53 by inhibiting its expression. Tumors with overexpression of MDM2 are linked to increased invasiveness, increased potential for metastasis, and resistance to radiation and chemotherapy. Death rates and recurrence rates for BC remain high despite individualized treatment protocols. In order to ascertain the elucidation of MDM2 IHC status in invasive ductal carcinoma and its relationship with tumor metastasis, tumor staging, lesion dimensions, lymph nodal staging, as well as hormone expression, this study has been undertaken. OBJECTIVES: 1)To determine the expression of MDM2 in invasive ductal carcinoma. 2)To determine association of MDM2 with histopathological parameters and hormonal expression in invasive ductal carcinoma. MATERIALS AND METHODS: This research has assessed ninety-three cases of infiltrating ductal carcinoma that were surgically resected. All patient H&E slides were examined, and MDM2 immunohistochemistry was conducted. Clinicopathological information about the cases, including age, tumor staging, histological tumor grading, nodal staging, extranodal extension, TNM staging, and hormonal expression, was assessed and correlated with MDM2 expression. xvi RESULTS: Patients in this study had an average age of about 53.7 years. Significant association was found between MDM2 and histological grading of tumor (MBR), tumor staging, nodal staging and TNM staging with a p-value of <0.001, <0.001, <0.001 and <0.028. There was no correlation that was statistically important reported with MDM2 & age group, size of the tumor, extra nodal staging, and NPI score. Majority of the tumors with Ki67 >14% showed an MDM2 score of 2 (39.7%) and 3 (29.3%) which implies that proliferative index was more in MDM2 positive cases and is statistically noteworthy with a p-value of 0.012. Among the four molecular types Luminal A and TNBC were determined to have a noteworthy statistical correlation having a probability value with 0.004 & 0.001 correspondingly, whereas no significant association was seen between Luminal-B and Her-2Neu Enriched. Most of the Luminal-A cases showed score of zero and 1 that is 21.9% and 46.9% respectively. Almost 60% of patients with TNBC showed a score of 3. CONCLUSION: MDM2 score reached its peak at 3 in TNM stage III and stage IV, indicating the enhanced aggressiveness of the tumor as the score increases. Prior treatment with MDM2 could potentially reduce the tumor burden and metastasis as most of the cases with MDM2 over expression was noted in subjects with extra nodal extension and higher TNM staging.