J Cancer 2012; 3:421-431. doi:10.7150/jca.4944

Research Paper

Prognostic Value of Proliferation Markers: Immunohistochemical Ki-67 Expression and Cytometric S-Phase Fraction of Women with Breast Cancer in Libya

Eramah Ermiah1,2✉, Abdelbaset Buhmeida3, Fathi Abdalla4, Ben Romdhane Khaled5, Nada Salem6, Seppo Pyrhönen1, Yrjö Collan7

1. Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Finland;
2. Department of Oncology, National Cancer Institute, Sabratha, Libya;
3. Center of Excellence in Genomic Medicine Research, King Abdul-Aziz University, Jeddah, Saudi Arabia;
4. Department of Pathology, Misurata Cancer Institute, Libya;
5. Department of Pathology, Salah Azaiz Cancer Institute, Tunis, Tunisia;
6. Department of Biochemistry, King Abdul-Aziz University, Jeddah, Saudi Arabia;
7. Department of Pathology, University of Turku, Turku, Finland.

Abstract

Background: We evaluated the association of the immunohistochemical Ki-67 expression, and S-phase fraction with clinicopathological variables and patient outcome.

Patients and methods: Histological samples from 100 primary Libyan breast carcinoma patients were retrospectively studied with monoclonal antibody to Ki-67. S-phase fraction was determined by DNA image cytometry.

Results: The median Ki-67 percentage for all tumors was 27.5%, ranging from 1 to 80% and the median S-phase fraction (SPF) was 11%, ranging from 0 to 62 %. Tumors with high Ki-67 expression were found in 76% of patients and with high SPF values in 56%. Ki-67 expression was more frequent in tumors with high SPF than low SPF. High Ki-67 and high SPF were associated with advanced stages, poor differentiation of tumors, positive lymph nodes, and distant metastasis. The Ki-67 was associated with hormone receptor negative tumors. The SPF was higher in young patients (<50 years) than in older patients. In the overall population (median follow-up 49 months), patients with high Ki-67 and high SPF had shorter survival time and predicted recurrence than patients with low Ki-67 and low SPF. In a Cox multivariate analysis, high SPF (p= 0.007), hormonal status (p= 0.001) and clinical stage (p=0.005) were independent predictors of disease-specific survival. The Ki-67 (p=0.065) in borderline significance proved to be independent predictor of disease-free survival. The SPF showed more statistically significance with a high grade of malignancy and survival time than Ki-67.

Conclusions: The SPF value is useful cell proliferation marker to assess tumor prognosis. These markers may reflect the aggressive behavior of Libyan breast cancer and predict of the recurrence. It is therefore important to take these markers into consideration to select a high risk subgroup of the patients for intensive treatment.

Keywords: Ki-67 expression, S-phase fraction, Libyan female breast cancer, prognosis

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How to cite this article:
Ermiah E, Buhmeida A, Abdalla F, Khaled BR, Salem N, Pyrhönen S, Collan Y. Prognostic Value of Proliferation Markers: Immunohistochemical Ki-67 Expression and Cytometric S-Phase Fraction of Women with Breast Cancer in Libya. J Cancer 2012; 3:421-431. doi:10.7150/jca.4944. Available from http://www.jcancer.org/v03p0421.htm