DOI QR코드

DOI QR Code

Ki67 Frequency in Breast Cancers without Axillary Lymph Node Involvement and its Relation with Disease-free Survival

Shandiz, Fatemeh Homaei;Shabahang, Hossein;Afzaljavan, Fahimeh;Sharifi, Nourieh;Tavasoli, Alireza;Afzalaghaee, Monavar;Roshanzamir, Emane;Pasdar, Alireza

  • Published : 2016.04.11

Abstract

Background: Breast cancer prognosis is influenced by several histopathology and clinical factors including expression of Ki67 which may have a predictive role in lymph node negative breast cancer patients. The aim of this study was to assess Ki67 expression in breast cancers without axillary lymph node involvement and to evaluate its prognostic value with regard to disease-free survival. Materials and Methods: Subjects were selected from non-metastatic invasive breast cancer patients who were referred to the oncology department of Ghaem hospital during 1 April 2001 to 1 April 2008. Ki67 levels were measured using immunohistochemistry (IHC) and compared with clinicopathological features. The relation of Ki67 expression with disease-free survival was also analysed. Results: A total of 106 women with a mean age of 49 were examined. Some 94.3% were classified as having invasive ductal carcinomas and the mean tumour diameter at the time of diagnosis was 2.8 cm. Some 50.9% of cases were ER positive and 47.2% were PR positive. P53 expression was positive in 48.1% of the cases. According to the IHC results, only 8.5% of the patients were Her2/neu positive. Ki67 was positive in 66 (62.3%) with a significant relation to lower age (p=0.0229) and P53 positivity (p=0.005). After an average of 40-months follow up, 13 (12.3%) demonstrated recurrence, most commonly systemic. Of 13 cases with relapse, 10 patients (77%) were Ki67 positive. Conclusions: In our population Ki67 appeared to be an independent prognostic factor for three-year survival. However, we stress that a survival study with a bigger sample size would help to support this conclusion.

Keywords

Breast cancer;Ki67;negative axillary lymph node;disease-free survival

References

  1. Colleoni M, Rotmensz N, Peruzzotti G, et al (2004). Minimal and small size invasive breast cancer with no axillary lymph node involvement: the need for tailored adjuvant therapies. Ann Oncol, 15, 1633-9. https://doi.org/10.1093/annonc/mdh434
  2. de Azambuja E, Cardoso F, de Castro G, et al (2007). Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer, 96, 1504-13. https://doi.org/10.1038/sj.bjc.6603756
  3. Gonzalez-Sistal A, Sanchez AB, Del Rio MC, et al (2014). Association between tumor size and immunohistochemical expression of Ki-67, p53 and BCL2 in a node-negative breast cancer population selected from a breast cancer screening program. Anticancer Res, 34, 269-73.
  4. Haroon S, Hashmi AA, Khurshid A, et al (2013). Ki67 index in breast cancer: correlation with other prognostic markers and potential in pakistani patients. Asian Pac J Cancer Prev, 14, 4353-8. https://doi.org/10.7314/APJCP.2013.14.7.4353
  5. Hezova R, Slaby O, Faltejskova P, et al (2010). microRNA-342, microRNA-191 and microRNA-510 are differentially expressed in T regulatory cells of type 1 diabetic patients. Cell Immunol, 260, 70-4. https://doi.org/10.1016/j.cellimm.2009.10.012
  6. Inwald EC, Klinkhammer-Schalke M, Hofstadter F, et al (2013). Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat, 139, 539-52. https://doi.org/10.1007/s10549-013-2560-8
  7. Jones S, Clark G, Koleszar S, et al (2001). Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients. Clin Breast Cancer, 1, 310-4. https://doi.org/10.3816/CBC.2001.n.005
  8. Kilickap S, Kaya Y, Yucel B, et al (2014). Higher Ki67 expression is associates with unfavorable prognostic factors and shorter survival in breast cancer. Asian Pac J Cancer Prev, 15, 1381-5. https://doi.org/10.7314/APJCP.2014.15.3.1381
  9. Kittaneh M, Montero AJ, Gluck S (2013). Molecular profiling for breast cancer: a comprehensive review. Biomarkers Cancer, 5, 61-70.
  10. Knutsvik G, Stefansson IM, Aziz S, et al (2014). Evaluation of ki67 expression across distinct categories of breast cancer specimens: a population-based study of matched surgical specimens, core needle biopsies and tissue microarrays. PLoS ONE, 9, 112121. https://doi.org/10.1371/journal.pone.0112121
  11. Kontzoglou K, Palla V, Karaolanis G, et al (2013). Correlation between Ki67 and breast cancer prognosis. Oncol, 84, 219-25. https://doi.org/10.1159/000346475
  12. Li FY, Wu SG, Zhou J, et al (2014). Prognostic value of Ki-67 in breast cancer patients with positive axillary lymph nodes: a retrospective cohort study. PLoS One, 9, 87264. https://doi.org/10.1371/journal.pone.0087264
  13. Mirza AN, Mirza NQ, Vlastos G, et al (2002). Prognostic Factors in Node-Negative Breast Cancer: A Review of Studies With Sample Size More Than 200 and Follow-Up More Than 5 Years. Ann Surg, 235, 10-26. https://doi.org/10.1097/00000658-200201000-00003
  14. Moriya T, Sakamoto K, Sasano H, et al (2000). Immunohistochemical analysis of Ki-67, p53, p21, and p27 in benign and malignant apocrine lesions of the breast: its correlation to histologic findings in 43 cases. Mod Pathol, 13, 13-8. https://doi.org/10.1038/modpathol.3880004
  15. Mousavi SM, Gouya MM, Ramazani R, et al (2009). Cancer incidence and mortality in Iran. Ann Oncol, 20, 556-63.
  16. Osman I, Scher HI, Drobnjak M, et al (2001). HER-2/neu (p185neu) protein expression in the natural or treated history of prostate cancer. Clin Cancer Res, 7, 2643-7.
  17. Payandeh M, Sadeghi M, Fekri A, et al (2014). P53 mutation compared with Ki67 marker in metastasis of breast cancer in western. Iran J Solid Tumors, 4, 4-9.
  18. Rossi L, Laas E, Mallon P, et al (2015). Prognostic impact of discrepant Ki67 and mitotic index on hormone receptorpositive, HER2-negative breast carcinoma. Br J Cancer, 113, 996-1002. https://doi.org/10.1038/bjc.2015.239
  19. Sahin AA, Ro J, Ro JY, et al (1991). Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis. Cancer, 68, 549-57. https://doi.org/10.1002/1097-0142(19910801)68:3<549::AID-CNCR2820680318>3.0.CO;2-J
  20. Sirvent JJ, Salvado MT, Santafe M, et al (1995). p53 in breast cancer. Its relation to histological grade, lymph-node status, hormone receptors, cell-proliferation fraction (ki-67) and c-erbB-2. Immunohistochemical study of 153 cases. Histol Histopathol, 10, 531-9.
  21. Stal O, Stenmark Askmalm M, Wingren S, et al (1995). p53 expression and the result of adjuvant therapy of breast cancer. Acta Oncol, 34, 767-70. https://doi.org/10.3109/02841869509127184
  22. Tanriverdi O, Meydan N, Barutca S (2014). Reconsideration of clinical and histopathological prognostic factors in breast cancer patients: a single center experience. Asian Pac J Cancer Prev, 15, 807-12. https://doi.org/10.7314/APJCP.2014.15.2.807
  23. Wexler MJ (2003). Role of axillary lymph-node dissection in the management of breast cancer. Canadian J Surg, 46, 247-50.
  24. Wolff AC, Hammond ME, Hicks DG, et al (2014). Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med, 138, 241-56. https://doi.org/10.5858/arpa.2013-0953-SA
  25. Wong H, Lau S, Cheung P, et al (2014). Lobular breast cancers lack the inverse relationship between ER/PR status and cell growth rate characteristic of ductal cancers in two independent patient cohorts: implications for tumor biology and adjuvant therapy. BMC Cancer, 14, 826. https://doi.org/10.1186/1471-2407-14-826