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The inactivation of p53 by mutations or other mechanisms favor genetic instability, which is the hallmark of tumor cells.
Immunohistochemistry (IHC) for p53 protein expression shows a pretty good, but not perfect, correlation with the status of the p53 gene. In general, the presence of immunoreactive p53 correlates the presence of p53 mutation, especially when the percent of immunoreactive cells exceeds 10-20% (depending on the study). This is because transcription of mutated p53 gene usually results in the production of a protein that is more stable than the wild type, and therefore it accumulates in the nucleus, which can be detected by IHC. There have been a plethora of studies correlating p53 IHC with clinicopathologic parameters in a variety of cancers. In prostate carcinoma, p53 immunopositivity has been reported to be associated with higher Gleason score, nuclear grade, pathologic stage, and the presence of metastatic disease. In head and neck squamous cancers, presence of abnormal p53 expression correlates with an increased risk of locoregional recurrence, resistance to radiotherapy and not surprisingly, risk of developing a second primary tumor. Nuclear accumulation of aberrant p53 has been detected in 40-75% of colorectal cancers, and is an independent indicator of poor prognosis in some studies. Similarly, in invasive breast cancers, up to 50% of which contain gene mutations, lack of functional p53 is associated with many aggressive biological factors and poor clinical outcome. Finally, in melanomas, p53 expression is associated with an increase in the depth of invasion in the primary tumor, and the presence of metastatic disease. These, and other studies, have convincingly validated the use of p53 IHC as a reliable assay for prognostication purposes.
Veripath OncoDiagnostics offers p53 as part of the standard breast and colorectal cancer panels, but it can also be ordered individually. In addition to surgical resections, this laboratory has extensive experience in evaluating cancer-related biomarkers such as p53 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. Elledge RM et al. The role and prognostic significance of p53 gene alterations in breast cancer. Breast Cancer Res Treat 27:95; 1993
2. Harris CC et al. Clinical implications of the p53 tumor suppressor gene. N Engl J Med 329:1318; 1993
3. Heidenberg HB et al. The role of p53 tumor suppressor gene in prostate cancer: a possible biomarker? Urology 48:971; 1996
4. Shin DM et al. p53 expression: predicting recurrence and second primary tumors in head and neck squamous cell carcinoma. J Natl Cancer Inst 88:519; 1996
5. Vogt T et al. p53 protein expression and Ki-67 antigen expression are both reliable biomarkers of prognosis in thick stage I nodular melanomas of the skin. Histopathology 30:57; 1997
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