Ki67 expression in triple negative breast cancer: Correlation of Ki67 expression with other prognostic factors in breast cancer in Indian patients
Abstract
Introduction: Triple negative breast cancer ( TNBC) cases are not sensitive to hormonal therapy and till date no specific targeted medication has been found for TNBC. The present study aims to know the expression of Ki67 in TNBC tissues and in non-TNBC tissues using immunohistochemistry and to do correlation analysis of ki 67 expression with other clinicopathological parameters.
Material and Methods: The present study was conducted on 160 cases of breast cancer received as specimens from January to august 2016 in the Pathology Department, Sri Guru Ram Das institute of medical sciences, Amritsar. Histopathological typing and grading was done followed by immunohistochemistry for ER, PR, Her2neu and ki67.
Results: Ki67-positive expression were identified in 86.6% TNBC cases (including 14 cases of strong Ki67 expression). By contrast, among 130 cases of non-TNBC, 98 cases were Ki67-positive, accounting for 75.3%,(only 2 cases showed strong positivity) indicating a significant difference compared with that in the TNBC group that Ki67 proliferation index was higher in the cases with size >2cm also cases with lymph node metastasis showed high Ki67 proliferation index.
Conclusion: Ki-67 index is relatively higher in TNBC than in non-TNBC cases. Ki67 expression correlated with tumor size and lymph node metastasis in breast cancer in the present study. Thus the increased expression of Ki67 may predict the increased proliferation of breast cancer cells, increased invasiveness, faste r rate of growth and the high incidence of lymph node metastasis.
Downloads
References
2. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ; Panel members. Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22(8):1736-47. doi: 10.1093/annonc/mdr304.
3. Prat A, Cheang MC, Martín M, Parker JS, Carrasco E, Caballero R, Tyldesley S, Gelmon K, Bernard PS, Nielsen TO, Perou CM. Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer. J Clin Oncol. 2013;31(2):203-9. doi: 10.1200/JCO.2012.43.4134.
4. Dawood S, Hu R, Homes MD, Collins LC, Schnitt SJ, Connolly J, Colditz GA, Tamimi RM. Defining breast cancer prognosis based on molecular phenotypes: results from a large cohort study. Breast Cancer Res Treat. 2011 ;126(1):185-92. doi: 10.1007/s10549-010-1113-7.
5. Wang GS, Zhu H, Bi SJ. Pathological features and prognosis of different molecular subtypes of breast cancer. Mol Med Rep. 2012(4):779-82. doi: 10.3892/mmr.2012.981. [PubMed]
6. Lund MJ, Trivers KF, Porter PL, Coates RJ, Leyland-Jones B, Brawley OW, Flagg EW, O'Regan RM, Gabram SG, Eley JW. Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res Treat. 2009;113(2):357-70. doi: 10.1007/s10549-008-9926-3. [PubMed]
7. Banerjee S, Reis-Filho JS, Ashley S. Basal-like breast carcinomas: clinical outcome and response to chemotherapy.. J Clin Pathol. 2006;59(7):729-35. doi:10.1007/s10147-008-0831-x. [PubMed]
8. Carey LA, Dees EC, Sawyer L. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13(8):2329-34. . doi:10.1158/1078-0432.CCR-06-1109.
9. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109(9):1721-8. [PubMed]
10. Carey LA, Perou CM, Livasy CA. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006;295(21):2492-502. doi:10.1001/jama.295.21.2492. [PubMed]
11. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15):4429-34. [PubMed]
12. Rosai J. The Breast. In: Rosai and Ackerman’s Surgical Pathology. 10th Edition (Vol. 2). New York: Mosby (Elsevier);2012.p.1719-20.
13. Harvey JM, Clark GM, Osbome CK, Allred DC. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cance. J Clin Oncol. 1999 ;17(5):1474-81 doi:10.1.1.452.3933.
14. Bauer, K. R., Brown, M., Cress, R. D, Parise, C. A. & Caggiano, V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109(9):1721-8.doi:10.1002/cncr.22618.
15. M. Dowsett, T.O. Nielsen, R. A’Hern, J. Bartlett, R.C. Coombes, J. Cuzick, M. Ellis, N.L. Henry, J.C. Hugh, T. Lively, L. McShane, S. Paik, F. Penault-Llorca, L. Prudkin, M. Regan, J. Salter, C. Sotiriou, I.E. Smith, G. Viale, J.A. Zujewski, D.F. Hayes, Assessment of Ki-67 in breast cancer: recommendations from the International Ki-67 in Breast Cancer working group. J Natl Cancer Inst. 2011 ;103(22):1656-64. doi: 10.1093/jnci/djr393.
16. Bhatavdekar JM, Patel DD, Shah NG, et al. Prognostic significance of immunohistochemically localized biomarkers in stage II and stage III breast cancer: a multivariate analysis. Ann Surg Oncol. 2000 ;7(4):305-11.
17. Kim T, Han W, Kim MK, Lee JW, Kim J Ahn SK, Lee HB, Moon HG, Lee KH, Kim TY, Han SW, Im SA, Park IA, Kim JY, Noh DY. Predictive Significance of p53, Ki-67, and Bcl-2 Expression for Pathologic Complete Response after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer. J Breast Cancer. 2015;18(1):16-21. doi: 10.4048/jbc.2015.18.1.16.
18. B. Keam, SA Im, KH Lee, SW Han, DY Oh, JH Kim, S.H. Lee, W Han, D Kim,TY Kim, I A Park, DY Noh, D S Heo, YJ Bang. Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis. Breast Cancer Res. 2011 ;13(2):R22. doi: 10.1186/bcr2834.
19. M. Miyashita, T. Ishida, K. Ishida, K. Tamaki, M. Amari, M. Watanabe, N. Ohuchi, H. Sasano, Histopathological subclassification of triple negative breast cancer using prognostic scoring system: five variables as candidates.Virchows Arch. 2011 ;458(1):65-72. doi: 10.1007/s00428-010-1009-2.
20. MA Aleskandarany, AR Green, AA Benhasouna, F FBarros, K R Neal, J R Reis- Filho, IO Ellis, EA Rakha, Prognostic value of proliferation assay in the luminal, HER2 positive and triple negative biological classes of breast cancer. Breast Cancer Res. 2012; 14(1):62.doi: 10.1186/bcr3084.