Comparative Analysis of Ki-67 in Different Scoring Patterns and its Association with other Prognostic Markers of Breast Carcinoma

Abstract

Introduction: Immunohistochemical evaluation of Ki-67 is widely used for estimation of tumour proliferation in breast cancer. Till date, no specific method or a cut-off point for Ki-67 exists. Aim: To perform a comparative analysis between different scoring patterns and mean Ki-67 value and association of mean Ki-67 with other prognostic markers like tumour size, lymph node status, tumour stage and grade and different molecular subtypes of breast cancer. Materials and Methods: A cross-sectional study was conducted at Dr. D.Y Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India, between August 2019 to August 2021. Total of 50 new diagnosed cases of breast cancer were studied for the histologic type, grade and stage of the tumour. Immunohistochemistry for Oestrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Factor Receptor 2 (HER2) and Ki-67 was performed. Association of Ki-67 with other prognostic markers like tumour size, lymph node status, tumour stage and grade and different molecular subtypes of breast cancer was evaluated by expressing Ki-67 as a continuous variable (mean±SD) and also by dividing Ki-67 into different scoring patterns (I: ≤14%, >14%, II: ≤15%, 16- 30%, >30% and III: <20%, 20-50%, ≥50%). Statistical tests like Kruskal-Wallis test (mean Ki-67 with tumour size, tumour grade and molecular subtypes), Mann-Whitney Rank Sum Test (mean Ki-67 with lymph node status) and Analysis of variance (ANOVA) (mean Ki-67 with staging) respectively. Results: Out of 50 patients, 40 (80%) were older than 50-yearold. Twenty six (52%) cases affected the left breast. A total of 49 (98%) were diagnosed as Invasive Ductal Carcinoma (IDC). Among them 26 (52%) cases were of grade III and 25 (50%) cases were of Luminal A. Mean Ki-67 and molecular subtypes of breast cancer had statistically significant association (p= 0.002). No association was found between mean Ki-67 and tumour size (p=0.608), lymph node status (p=0.506) stage (p=0.979) and grade (p=0.095) of the tumour. Although scoring pattern I and III had no remarkable findings. Notably, scoring pattern II showed higher tumour sizes, lymph node positivity, higher stage and grade and basal-like tumours demonstrated a higher Ki-67 index. Conclusion: Evaluation of Ki-67 as a continuous variable yielded significant association with other prognostic markers of breast cancer. There was no single “best” scoring pattern identified. A direct association of Ki-67 was found with molecular subtypes of breast cancer.