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Ki-67 Biomarker Expression and Its Relationship with Metastasis Time and Location in Breast Cancer Patients
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Abdolreza Fazel1    , Seyed Reza Khandoozi *2 , Gholamreza Roshandel3 , Ashour Kor4 |
1- Associate Professor of Surgery, Cancer Research Center, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
2- Assistant Professor, Cancer Research Center, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. , dr.khandoozi@goums.ac.ir
3- Associate Professor, Golestan Research Center of Gastroenterology and Hepatology, Jorjani Clinical Sciences Research Institute, Golestan University of Medical Sciences, Gorgan, Iran.
4- General Physician, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. |
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Keywords: Breast Neoplasms [MeSH], Biomarkers [MeSH], Ki-67 Antigen [MeSH]
Article ID: Vol27-24 |
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Full-Text [PDF 544 kb]
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Type of Study: Original Articles |
Subject:
Oncology
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Abstract: (8 Views) |
Extended Abstract
Introduction
Breast cancer is the most common cancer in women, accounting for 33% of all cancer cases. Despite numerous advances in the early diagnosis and appropriate treatment of this disease, approximately 50,000 affected women develop metastasis annually. Breast cancer is the second leading cause of cancer-related death in the United States. Moreover, in recent decades, the incidence rate of breast cancer has increased, particularly in women under the age of 50. This cancer alone accounts for 29% of new cancer cases in women in the United States. The incidence rate of breast cancer has continued its upward trend, increasing by one percent annually during 2012-2021.
From a histological perspective, breast cancer is broadly classified into two main groups: In situ and invasive. The breast tissue is composed of two parts: The lobules and the ducts that connect the lobules to the nipple. Breast cancer is further categorized into lobular and ductal types depending on which of these parts is involved. Over 80% percent of invasive breast cancers are of the ductal type, with the remainder being lobular.
Metastasis is the end-product of a multi-step cellular process called the invasion metastasis cascade. This process involves the dissemination of cancer cells to other organs and their subsequent adaptation to the micro-environments of the target tissue. Many genes are involved in this process. Genes activated in breast cancer fall into two categories: a) Genes called tumor suppressors, which inhibit tumor growth, and b) genes like Ki-67, which promote or accelerate tumor growth. The Ki-67 gene is located on the long arm of human chromosome 10. Its product is a non-histone protein called proliferating cell nuclear antigen (PCNA), which has a half-life of approximately 60 to 90 minutes. Ki-67 is also used as an important marker in cancer prognosis and prediction.
Ki-67 is a non-histone nuclear protein found exclusively in vertebrates and is considered an indicator of high cellular proliferation. A level below 15% is regarded as a tumor with low cellular proliferation, while a level above 15% is considered a criterion for tissue cell proliferation. The measurement of this protein serves as a biomarker in various malignant tumors throughout the body, particularly in breast cancer at different stages of the disease, either as a baseline measurement or on a new tissue sample at the metastasis time.
Given the importance of determining prognosis and the role of biomarker levels, this study was conducted to determine the expression level of the Ki-67 biomarker and its relationship with metastasis time and location in breast cancer patients.
Methods
This descriptive-analytical study was conducted on 154 women with breast cancer admitted to the Fifth Azar Educational-Therapeutic Center in Gorgan, Iran, during 2009-2019. The inclusion criterion comprised patients presenting with metastasis. The exclusion criteria included patients with distant metastasis at the time of initial diagnosis and/or those with incomplete medical records. Informed consent was obtained from all patients. The patients' records were extracted by referring to the patients' medical records and statistics database. Patient information was entered into the checklist in two sections: Demographic characteristics and information related to the study variables (age, gender, metastasis location, percentage of Ki-67 expression level in the immunohistochemistry (IHC) method, cancer stage at the time of diagnosis, metastasis time of occurrence, and breast cancer subtype. The measurement of these indices was performed by a single individual, at one location, and with a single device, using a standard method upon admission. Tissue Ki-67 levels were measured in all patients and divided into two groups: Less than 15% and equal to or greater than 15%. Patients were also categorized into three age groups of under 40 years old, 40–60 years old, and over 60 years old.
Results
A total of 63% of the patients were in the 40-60 year age group, 30.5% were under 40 years old, and 6.5% were over 60 years old. Forty-five patients (29.2%) had Ki-67 levels below 15%, and 109 (70.8%) had Ki-67 levels above 15%. No statistically significant correlation was found between the age group and the tissue Ki-67 percentage.
There was no statistically significant relationship between tissue Ki-67 serum levels and metastasis location, nor between tissue Ki-67 serum levels and the disease stage at the time of diagnosis. The relationship between the time interval from disease onset to metastasis diagnosis and the tissue Ki-67 level was investigated, and a statistically significant relationship was found between them (P<0.043).
Conclusion
Based on the results of this study, the percentage of Ki-67 expression was higher with a longer interval between disease onset and metastasis. This finding aligns with some studies, meaning that Ki-67 expression level has been higher in patients with advanced and metastatic cancer.
In the current study, the Ki-67 level did not differ significantly across the three age groups. There was no statistically significant correlation between Ki-67 level serum and disease stage. The Ki-67 level was not statistically significantly correlated with age group, metastasis location, and breast cancer stage, and was only significantly correlated with the time interval between disease onset and metastasis. A more regular and shorter follow-up schedule may be considered for patients with high Ki-67 expression. However, studies with larger sample sizes or multicenter designs are suggested to determine the necessity or impact of intensive treatment.
Ethical Statement
This study was approved by the Research Ethics Committee of Golestan University of Medical Sciences (IR.GOUMS.REC.1401.326). Patient information was kept confidential, and all necessary measures were taken for those requiring treatment or guidance.
Conflicts of Interest
No conflict of interest.
Acknowledgments
This article has been extracted from the M.D dissertation (No. 200) of Mr. Ashour Kor in Medicine at the School of Medicine, Golestan University of Medical Sciences. We hereby sincerely thank all those who collaborated in the execution of this study.
Authors' Contributions
Abdolreza Fazel (M.D): Project administration and design, Approval of the final manuscript.
Seyed Reza Khandoozi (M.D): Project administration and design, Project execution, Interpretation of the results, Drafting of the initial manuscript, Approval of the final manuscript.
Gholamreza Roshandel (M.D, Ph.D): Data analysis, Interpretation of the results, Approval of the final manuscript.
Ashour Kor (M.D): Project administration and design, Project execution, Data collection, Drafting of the initial manuscript.
Key Message: Individuals with tissue Ki-67 levels above 15% experience metastasis within a shorter period of time.
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Fazel A, Khandoozi S R, Roshandel G, Kor A. Ki-67 Biomarker Expression and Its Relationship with Metastasis Time and Location in Breast Cancer Patients. J Gorgan Univ Med Sci 2025; 27 (3) :32-38 URL: http://goums.ac.ir/journal/article-1-4478-en.html
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