Proliferation-Related Ki-67 Antigen

Alternative Names

  • MKI67
  • Antigen Identified by Monoclonal Antibody Ki-67
  • KIA
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OMIM Number

176741

Gene Map Locus
10q25-qter

Description

Ki-67 antigen (KIA) is a nuclear protein that is expressed in proliferating cells, and thus can be used as a biomarker for proliferation. This protein is actively expressed during the G1, S, G2, and M phases of the cell cycle, while only a basal undetectable level of expression is seen in the G0 phase. Unlike the PCNA biomarker, KIA is not involved in any of the DNA repair processes, and is therefore, a more accurate indicator of the proliferative state of the cell. The percentage of Ki-67 positive cells in a tissue sample gives rise to the Ki67 index, which is used to estimate the number of growing cells in the neoplasm. Although the exact function of the protein is not known, it seems that it has some role in maintaining cellular proliferation.

Earlier Ki-67 antibodies could only be used in frozen or fresh tissue samples, and therefore caused serious difficulties in the assays. However, a monoclonal antibody against KIA, known as MIB-1 antibody, was later produced, which can be used with paraffin or formalin embedded tissues. KIA has since been used as a proliferation marker for both diagnostic and prognostic purposes in prostate cancer, benign menigiomas, non small cell lung carcinoma, ovarian cancer, and squamous cell carcinoma, and many other neoplastic growths.

Molecular Genetics

The gene encoding KIA is located on the long arm of chromosome 10, where it spans a total length of around 30 kb, with its 14 coding exons. KIA consists of 3256 amino acids and weighs about 360 kDa. The protein is localized to the nucleus after expression. In the G1 phase, it is localized to the perinucleolar region, whereas later in the cell cycle, it can be detected throughout the nuclear matrix. During mitosis, KIA is detected on all the chromosomes.

Epidemiology in the Arab World

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Other Reports

Oman

Al-Moundhri et al. (2005) determined the prognostic effect of several tumor suppressor and biomarker proteins in Arab patients diagnosed with gastric carcinoma and studied the association of their expression with the clinico-pathological features. KIA expression was determined in 121 paraffin-embedded tumor blocks prepared from patients diagnosed with gastric cancer (mean age was 60.2 years, with 68.6% of the tumors being deeply penetrating T3 and T4 and 71% of the patients had advanced stages III and IV) in the period of 1995 to 2002 by immunohistochemical staining using Ki67 monoclonal antibodies. Over-expression of KIA (more than 25% of the tumor cells showed nuclear staining) was found in 69.4% of the samples, and a strong correlation between p53, p27 kip1, and Ki67 was detected. Both p53 and Ki67 over-expression were seen in patients less than 60 years.

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