Profile of mRNA Expression of Ki-67 in Breast Cancer Patients Pre- and Post- Chemotherapy

Abstract

Abstract:Background: Proliferation is a distinct hallmarks of cancer. Ki-67 designated as a marker of proliferation in solid tumors. The proliferative activity of tumor demonstrated by expression of Ki-67 in breast cancer has been associated with a poor prognosis. Changes in the relative proportions of Ki-67 can be observed during chemotherapy and may correlated with clinical response in breast cancer. Purpose: Evaluate changes in mRNA expression of proliferation marker Ki-67 in breast cancer patients pre-and post-chemotherapy in relation with clinical response to chemotherapy. Method: This is a longitudinal study, 30 subjects breast cancer tissue samples pre-and post-chemotherapy using cyclophosphamide, adriamycin, 5FU regiment. We using qRT-PCR techniques to detect mRNA expression of Ki-67. Chemotherapy response is calculated using RECIST criteria. Results: Mean value of Ki-67 mRNA expression on breast cancer patients pre-chemotheraphy was 11.837±0.360. Mean value of Ki-67 mRNA expression on breast cancer patients post-chemotheraphy was 11.241±1.971. There was no significant correlation between expression of Ki-67 mRNA prechemotherapy with clinical response to chemotherapy, p = 0.862 (p ≥0.05). There is a positive correlation between velocity of Ki-67 mRNA expression with clinical response with value of r = 0.378, this correlation was significant with p = 0.020 (p<0.05). Conclusion: Chemotherapy cause decrease in mRNA expression of Ki-67. There is insignificant correlation between expression of mRNA Ki-67 baseline with chemotherapy response. Velocity of Ki-67 mRNA expression has significant correlation with clinical response to chemotherapy.

Ki-67 Expression by Immunohistochemistry and Quantitative Real-Time Polymerase Chain Reaction as Predictor of Clinical Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

“…But, chemotherapy cause decrease in mRNA expression of Ki-67. The rate of Ki-67 mRNA expression has a significant correlation with clinical response to chemotherapy [ 17 , 34 ].…”

“…mRNA expression of Ki-67 is a predictor of the achievement of complete pathological response and better than Ki-67 expression which was detected by immunohistochemistry [ 39 ]. Ki-67 mRNA expression level is more objective and highly reproducible quantification of proliferation activity and more meaningful than Ki-67 protein expression by immunohistochemistry, either by visual scoring or by quantitative image analysis [ 17 , 39 ].…”

“…Then vortexing and centrifugation for 30 seconds at a speed of 13,000 rpm were conducted, and the supernatant was taken. The supernatant from this process will result in nucleotide extraction and was stored at −800°C before PCR analysis [ 16 , 17 ].…”

“…Reactions were centrifuged briefly, and the reaction was placed in the instrument, and the PCR program is ready to run using real-time PCR machine (CFX Connect System, Bio-Rad Laboratories, real-time PCR 96-well 0,1 ml, USA). Each sample was measured in triplicate [ 17 – 19 ].…”