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Unlike proliferating cell nuclear antigen (PCNA), which not only has a role in DNA replication, but also DNA repair, Ki-67 is virtually restricted in its role as a proliferation antigen, making it a more specific determinant of growth fraction. Needless to say, it is more sensitive than the old-fashioned assessment of mitotic figures for determining proliferation. MIB-1 is the monoclonal antibody developed against the Ki-67 antigen that can be used on routinely fixed paraffin tissue after microwave antigen retrieval.
Numerous studies over the last decade have convincingly established the validity of assessing the Ki-67 antigen-expressing fraction ("MIB-1 labeling index") in tumors as a surrogate for growth fraction, and correlated this value with a variety of clinicopathologic parameters. The prognostic value of the MIB-1 labeling index (MLI) is of greatest value in those tumors where the clinical course is difficult to predict by histologic parameters alone. For example, in breast cancers, MLI is an independent correlate of both overall survival and disease recurrences, while in resected non-small cell lung cancers a high MLI is associated with poor postoperative five-year survival. On the same lines, in prostate cancer, multivariate analysis has shown MLI to be an independent predictor of disease free survival, as well as treatment refractoriness and disease recurrence, irrespective of stage and histologic grade. Irrespective of tumor site or histology, a high MLI thus appears to correlate with unfavorable clinical outcome in either univariate or multivariate analyses.
Veripath OncoDiagnostics offers MIB-1 on routine archival material as a standard component of all cancer panels. In addition to surgical resections, this laboratory has extensive experience in evaluating cancer-related biomarkers such as MIB-1 in needle core biopsies, which facilitates preoperative risk stratification. Currently, we are using an automated image analysis system to quantitatively score percentage positivity and intensity grade finally reflected in a histoscore on each evaluation. For more information contact Dr Raheela Ashfaq at Veripath OncoDiagnostics at 214.645.7053 or Raheela.Ashfaq@UTSouthwestern.edu.
Selected references:
1. Aaltomaa S et al. Value of Ki-67 immunolabeling as a prognostic factor in prostate cancer. Eur Urol 32:410; 1997
2. Bettencourt MC et al. Ki-67 expression is a prognostic marker of prostate cancer recurrence after radical prostatectomy. J Urol 156:1064; 1996
3. Biesterfeld S et al. Rapid and prognostically valid quantification of immunohistochemical reactions by immunohistochemistry of the most positive tumor focus. J Pathol 185:25; 1998
4. Jansen RL et al. MIB-1 labeling index is an independent prognostic marker in primary breast cancer. Br J Cancer 78:460; 1998 Scholzen T et al. The Ki-67 protein: from the known and the unknown. J Cell Physiol 182:311; 2000
5. Shiba M et al. Ki-67 immunostaining and other prognostic factors including tobacco smoking in patients with resected nonsmall cell lung carcinoma. Cancer 89:1457; 2000 |
