Thursday, February 18, 2016

Immunohistochemical surrogate for TP53 mutation

Quoted highlights on IHC mutational surrogates from: Tanboon J, Williams EA, and Louis DN. The Diagnostic Use of Immunohistochemical Surrogates for Signature Molecular Genetic Alterations in Gliomas. J Neuropathol Exp Neurol Vol. 75, No. 1, January 2016, pp. 4–18:

Because they are rare in nonneoplastic brain lesions, TP53 mutations can be used as a marker to differentiate glioma from gliosis.

TP53 alterations ... are essentially mutually exclusive with 1p/19q codeletion.

- Tumorigenic TP53 mutations have been reported to be present in > 50% of gliomas with astrocytic features, including 59%–74% of diffuse astrocytomas, 53%–65% of anaplastic astrocytomas, and 62%–65% in secondary glioblastomas. In contrast, these mutations are less common in gliomas with oligodendroglial features (9%–44%), and in primary glioblastomas (23%–28%).

Intense nuclear staining for p53 protein by immunohistochemistry in a substantial percentage of tumor cells has long been used as a surrogate marker for TP53 mutations. The underlying mechanism is abnormally elongated half-lives for the protein products of the most common TP53 mutations in gliomas. 

Strong p53 nuclear positivity in > 10% of the tumor cells is the most accurate predictor for TP53 mutations in gliomas.

- Positivity of p53 immunohistochemistry staining can occur in [non-neoplastic] conditions of cellular stress, [causing false positive results].

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