Dataset Information

Immunohistochemical over expression of p53 in head and neck Squamous cell carcinoma: clinical and prognostic significance.

ABSTRACT:

Objective

Immunohistochemical over expression of p53 is considered as a marker of poor prognosis in many cancers. Therefore, we aimed to evaluate immunohistochemical overexpression of p53 in 121 cases of head and neck Squamous cell carcinoma and its association with various clinicopathologic features and survival.

Results

Total 66.1% (80 cases) expressed positive p53 expression, 34% (29 cases) revealed no p53 expression, while focal positive p53 expression was noted in 9.9% (12 Cases). Moreover, high p53 expression (>?70%) was noted in 26.4% (32 cases), while 19% (23 cases) showed 51-70% p53 expression. On the basis of intensity of p53 staining; strong p53 expression was noted in 39.7% (48 cases), while 24.8% (30 cases) and 10.7% (13 cases) revealed intermediate and weak p53 expression respectively. Significant association of p53 intensity of expression with extranodal extension and higher tumor grade (grades II and III) was noted. p53 is useful prognostic biomarker in head and neck Squamous cell carcinoma and therefore we suggest that more large scale studies are needed to evaluate its prognostic significance in our population.

SUBMITTER: Hashmi AA

PROVIDER: S-EPMC6029369 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Immunohistochemical over expression of p53 in head and neck Squamous cell carcinoma: clinical and prognostic significance.

Hashmi Atif Ali AA Hussain Zubaida Fida ZF Hashmi Shumaila Kanwal SK Irfan Muhammad M Khan Erum Yousuf EY Faridi Naveen N Khan Amir A Edhi Muhammad Muzzammil MM

BMC research notes 20180703 1

<h4>Objective</h4>Immunohistochemical over expression of p53 is considered as a marker of poor prognosis in many cancers. Therefore, we aimed to evaluate immunohistochemical overexpression of p53 in 121 cases of head and neck Squamous cell carcinoma and its association with various clinicopathologic features and survival.<h4>Results</h4>Total 66.1% (80 cases) expressed positive p53 expression, 34% (29 cases) revealed no p53 expression, while focal positive p53 expression was noted in 9.9% (12 Ca ...[more]

PMID: 29970180

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Project description:BackgroundWe conducted an analysis of previous adenoviral p53 (Ad-p53) treatment data in recurrent head and neck squamous cell carcinoma (HNSCC) patients to identify optimal Ad-p53 treatment methods for future clinical trials.MethodsThe analysis involved recurrent HNSCC patients treated with Ad-p53 for whom p53 genotyping and immunohistochemistry tumor biomarker studies had been performed (n = 70). Ad-p53 tumor treatment responses defined by RECIST 1.1 criteria were correlated with Ad-p53 dose and tumor p53 biomarkers. Gene expression profiles induced by Ad-p53 treatment were evaluated using the Nanostring IO 360 panel.ResultsAd-p53 dose based upon the injected tumor volume had a critical effect on tumor responses. All responders had received Ad-p53 doses greater than 7 × 1010 viral particles/cm3 of tumor volume. There was a statistically significant difference in tumor responses between patients treated with greater than 7 × 1010 viral particles/cm3 compared to patients treated at lower Ad-p53 doses (Tumor Response 31% (9/29) for Ad-p53 > 7 × 1010 viral particles/cm3 versus 0% (0/25) for Ad-p53 < 7 × 1010 viral particles/cm3; p = 0.0023). All responders were found to have favorable p53 biomarker profiles defined by less than 20% p53 positive tumor cells by immunohistochemistry (IHC), wild type p53 gene sequence or p53 deletions, truncations, or frame-shift mutations without functional p53 tetramerization domains. Preliminary gene expression profiling results revealed that Ad-p53 treatment increased interferon signaling, decreased TGF-beta and beta-catenin signaling resulting in an increased CD8+ T cell signature which are associated with increased responses to immune checkpoint blockade.ConclusionsOur findings have important implications for future p53 targeted cancer treatments and identify fundamental principles to guide Ad-p53 gene therapy. We discovered that previous Ad-p53 clinical trials were negatively impacted by the inclusion of patients with unfavorable p53 biomarker profiles and by under dosing of Ad-p53 treatment. Future Ad-p53 clinical trials should have favorable p53 biomarker profiles inclusion criteria and Ad-p53 dosing above 7 × 1010 viral particles/cm3 of injected tumor volume. Preliminary gene expression profiling identified p53 mechanisms of action associated with responses to immune checkpoint blockade supporting evaluation of Ad-p53 in combination with immune checkpoint inhibitors.

Dataset Information

Immunohistochemical over expression of p53 in head and neck Squamous cell carcinoma: clinical and prognostic significance.

Objective

Results

Publications

Immunohistochemical over expression of p53 in head and neck Squamous cell carcinoma: clinical and prognostic significance.

Similar Datasets

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