Abstract

Background: Breast cancer is the most common of all cancers and is the leading cause of cancer deaths in women worldwide, accounting for >1.6% of deaths and case fatality rates are highest in low-resource countries. Prognostic factors include the type of tumor, size of the tumor, tumor grade, number of involved lymph nodes, Ki67 status (cellular marker for proliferation), and the patient's age. Numerous studies have been conducted on these prognostic factors and their relationships with one another, however, the studies have not reported proper association of Ki67 proliferative index with other clinicopathological parameters. Breast cancer aggressiveness can be correlated with proliferation status of tumor cells, which can be obtained with Ki67 marker. the present study is considered to analyze the association of Ki67 with tumor size, lymph node involvement, histological grade, ER, PR, HER2 status in breast carcinoma.These predictive and prognostic factors help us to stage, plan and choose an appropriate mode of management that increases the patients longevity and improves their quality of life.

Methods: In this prospective observational study, all the excised mastectomy specimens of patients with carcinoma breast were processed. Histological Grading of tumor was done based on modified Bloom and Richardson score and lymphovascular invasion, surgical margin status and metastatic lymph node deposits were noted. Paraffin blocks were selected for immunohistochemistry and four marker panel including ER, PR, HER2 and proliferative index Ki67 were done and studied along with controls.The parameters used were: age, tumor size, stage of the disease, number of lymph nodes positive, HPE grade, ER, PR, HER2, Ki67. Statistical analysis was done.

Results: Total 41 cases were taken for the study. Patients age ranged between 25 to75 years, most were between 40-50 years of age. The mean age of presentation was 49.22±11.21years. 75.6% patients had Ki67 between 22-40% indicating that younger the age group more aggressive is the breast cancer. Ki67 expression decreased as the patient's age increased. Tumors were between 1.6 to 10cm in size in greatest dimension and most were between 3 to 6 cm. As tumor size increased, an increased expression level of Ki-67 was noticed. A positive relationship was observed between involved lymph nodes and the mean level of Ki67 expression. On histopathological examination tumour grade-III had high Ki67 and proliferative index was gradually increasing from grade-I to grade-III. Proliferative index Ki67 was also compared with stage of disease in non metastatic breast cancer, it was found to be higher in later stage of disease. This study demonstrated HER2/-neu positivity with higher frequency of Ki67. A significant relationship was also found between Ki67 and tumor grade and age of the patient.A positive relationship was observed between the mean level of Ki67 expression and involved lymph nodes.Ki67 expression thus affects the prognosis of breast cancer along with other factors, including the size and grade of tumor.

Conclusion: Ki-67 expression along with IHC markers for ER, PR and HER2neu is known to be correlating with histopathological grades, but was shown to be an independent prognostic and predictive factor in carcinoma of breast. High index labelled Ki67 is considered as an unfavourable factor that influences tumour progression and is associated with poorer prognosis. It helps in counselling the patient about prognosis of the disease. In conclusion, Ki-67 has great potential as prognostic biomarker in aggressive breast cancers and such prognostic information could be beneficial for development of therapeutic strategy. It would be easy to include it in the panel of markers routinely assessed in clinical practice.

Keywords: Carcinoma breast, Ki67, Prognostic biomarker, Histopathology, IHC.