Field cancerization in head and neck squamous cell carcinoma: immunohistochemical expression of p53 and Ki67 proteins: clinicopathological study (original) (raw)

Significance of p53 Gene Expression and Its Correlation with Various Clinico-Pathological Parameters in Head and Neck Squamous Cell Carcinomas

IOSR Journals , 2019

Background: Head and neck cancers are one of the leading cancers by incidence and mortality worldwide, mostly involving the mouth and oropharynx. Despite intense research, its 5-year survival rate remains low. p53 expression has been studied extensively in head and neck squamous cell carcinoms but its utility as a prognostic biomarker is still unclear. Aim: Assessment and clinicopathological correlation of p53 expression in head and neck squamous cell carcinoma. Methods: This prospective study was conducted at Kalinga Institute of Medical Sciences and Pradyumna Bal Memorial Hospital, Bhubaneswar, Odisha in the Department of Pathology for a period of two years and 56 cases were included. p53 expression and its correlation with the various clinicopathological parameters was studied by IHC. The obtained results were analyzed using chi-square test and a p-value of <0.05 was considered significant. Results: In this study out of 56 cases of head and neck squamous cell arcinomas, p53 expression was found in 37 (66.07%) cases. A significant correlation was found between p53 expression and site of origin of the tumour (p=0.014) as well as nodal metastasis (p=0.039). p53 expression did not show any significant correlation with age,sex, the risk factors (alcohol consumption, paan chewing and smoking), grade or tumor staging. Conclusion: p53 expression was observed in majority of cases originating from buccal mucosa and it may serve as a predictor of lymph node metastasis and eventual aggressiveness in head and neck squamous cell carcinomas.

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

BMC research notes, 2018

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. 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 ...

p53 Immunoexpression as a Prognostic Indicator of Survival in Head and Neck Squamous Cell Carcinoma

American Journal of Medicine and Medical Sciences, 2020

Background: Morbidity and mortality of head and neck squamous cell carcinoma (HNSCC) remain substantial across the globe. Despite all the considerable technical efforts and intensive therapeutics, HNSCC survival rates have not improved significantly over the past two decades. HNSCC are subject to various recommendations for early detection and management in order to control this devastating disease. Therefore, it is essential to ascertain new prognostic molecular markers which may help to recognize the biological behaviour of the tumor and identify patients with high risk of disease recurrence. The aberrations in the p53 pathway in HNSCC imply that molecular and immunohistochemical analysis (IHC) of this critical tumour suppressor marker may be of diagnostic and prognostic utility in the clinical management of the disease and improve the survival of HNSCC patients. Aim & objective: The prospective study was aimed to determine the association of p53 protein expression in HNSCC cases with certain clinicopathological variables, disease recurrence, overall survival and disease free survival and to assess whether tumor suppressor p53 protein has any prognostic significance in primary HNSCC. Materials & Methods: Expressions of p53 protein were assessed in a series of hundred histopathologically diagnosed, surgically treated, randomly selected and formalin fixed paraffin embedded (FFPE) biopsy specimens of HNSCC by IHC procedure. Clinical and histopathological data were gathered and patients were followed up for one year/death from the date of surgery. Pearson chi-square test/ Fisher exact test were used to explore the statistical associations of p53 protein expression with clinicopathological parameters and disease recurrence of HNSCC. In order to investigate the relevance of p53 staining with overall survival and disease free survival, survival analysis was performed by using Kaplan-Meier log rank test. Results and Conclusion: The positive nuclear immunoexpression of p53 was found in 70% of the investigated malignancies, using a threshold of 10% stained cell nuclei. Out of 100 HNSCC cases, 41 died and 16 had disease recurrence during one year follow up. Statistically significant associations were observed for individual tumor stage (p = 0.010), early and advanced tumor stage (p = 0.004) and lymph node involvement (p = 0.028) with p53 immunoexpression. However, no significant correlation was found between p53 immunostaining and disease recurrence (p = 0.634), overall survival (p = 0.556) and disease free survival (p = 0.608) in HNSCC. Thus, our findings suggest that p53 serves as a poor potential prognostic biomarker in HNSCC. Clinical implications and prognostic relevance of p53 expression in HNSCC needed further studies to evaluate its role as a potential tumor marker.

Can p53 expression and staining intensity correlate with histopathological prognostic parameter and clinical staging in head and neck squamous cell carcinoma?

Journal of Pathology of Nepal

Background: : In recent years, p53 has emerged as an important tool for not only diagnosis and predicting prognosis in head and neck squamous cell carcinoma. The aim of this study was to find the role of p53 staining intensity in determining prognosis. Materials and Methods: Fifty histopathologically proven cases of squamous cell carcinoma of head and neck were studied. The findings of the study were analyzed particularly in reference to p53 expression and their correlation with age, sex, anatomical site, tumor size, histological grading, vascular, peri-neural, muscle invasion, lymph node metastasis and staining intensity. Results: Immunopositivity rate of p53 was 64% with percentage positive cells varying from 5-76% with mild, moderate and strong staining intensity. A positive correlation of p53 independently was seen with oral cavity, grade, lymph node metastasis and pathological staging. Conclusion: p53 immunoexpression is an important independent variable of prognostication.

P53 Overexpression in Head and Neck Squamous Cell Carcinoma: Review of the Literature

European journal of cancer. Part B, Oral oncology, 1996

As a tumour suppressor gene, the inactivation of p53 induces the development of numerous human cancers. Mutations of p53 have been implicated in the pathogenesis of head and neck squamous cell carcinoma (HN-SCC) at a high incidence. In premalignant lesions and in situ carcinomas, p53 overexpression is not exclusively restricted to neoplastic cells, but frequently affects the normal appearing keratinocytes adjacent to p53 positive neoplasms or present in dysplastic areas. These results suggest that as contributors to the early phases of HN-SCC development, p53 alterations may be excellent biomarkers that indicate the predisposition of a particular oral cavity premalignant lesion toward malignancy. In most cases, the p53 overexpression status of a tumour metastasis is identical to that of a primary tumour, indicating that a p53 mutation precedes metastatic spread. In patients with multiple primary tumours, multiple foci of p53 overexpression are observed in epithelia distant from the ...

Immunoexpression of p53 and ki-67 correlated with clinicopathological parameters in predicting recurrence of oral squamous cell carcinoma

Asian Journal of Medical Sciences

Background: Prognosis of oral squamous cell carcinoma (OSCC) can be predicted by evaluating both clinicopathological parameters and molecular markers. Understanding the reasons of recurrence is important to increase the morbidity and mortality of the patient. Objectives: The objectives are to study the immunoexpression of p53 and Ki-67 in recurrent and non recurrent OSCC. And correlate the clinicopathological parameters among non-recurrent and recurrent OSCC to predict the prognosis of OSCC. Methods: Clinicopathological and immunoexpression of p53 and Ki-67 at the histologically negative margin (HNM) and invasive tumor front (ITF) were assessed in 50 cases of non-recurrent and recurrent OSCC. Overall survival and disease free survival was estimated. Statistical tests like Mann Whitney U test, t Test, Pearson correlation coefficient, Kaplan Meier curve and Log Rank test were used. Results: The Labelling Index (LI) of p53 and Ki-67 was marginally higher in recurrent than in non-recurr...

Mutation of p53 in Squamous Cell Cancer of the Head and Neck: Relationship to Tumor Cell Proliferation

Laryngoscope, 1997

Rapid proliferation of squamous cell carcinomas of the head and neck (SCCHN) during therapy may contribute to treatment failure. We have investigated the presence of p53 abnormalities in patients with SCCHN as a correlate of proliferation rate and other pathologic and clinical variables. p53 Mutation, as determined by polymerase chain reaction and single-strand conformation polymorphism analysis of microdissected frozen sections of tumor biopsies, was significantly associated with a high labeling index, as determined by in vivo infusion of IUdR and BrdU (P = 0.017). p53 Protein expression was detected by immunohistochemistry with two different antibodies, followed by quantitative image analysis. Many cases exhibited strong p53 protein expression in the absence of mutations within the conserved region of the gene, and expression was not related to proliferation. The presence of p53 mutations was related to tumor differentiation in this group of patients.

Expression of p53 isoforms in squamous cell carcinoma of the head and neck

European Journal of Cancer, 2007

Recent data indicate that, similar to p63 and p73, several different p53 isoforms can be produced in humans through alternative initiation of translation, usage of an internal promoter and alternative splicing. These isoforms are reported to have varying functions and expressions. In squamous cell carcinoma of the head and neck (SCCHN), disruption of the p53 pathway is one of the most common genetic alterations. However, to our knowledge, no studies regarding the expression of different p53 isoforms in SCCHN have so far been performed. We screened for the expression of different p53 isoforms in SCCHN and clinically normal oral epithelia using nested RT-PCR. p53 mRNA was expressed in all tumours, all matched clinically normal tissue adjacent to the tumour and in buccal mucosa from healthy volunteers. Of the novel isoforms, p53beta was detected in the majority of samples analysed, and all of the recently described isoforms were also detected in at least some tumour and normal epithelium samples, with the exception of Deltap53 isoforms. We conclude that p53 variant mRNAs are expressed in both normal oral stratified epithelium and SCCHN. Improvements in methodologies and reagents to detect and quantify p53 isoform expression in clinical material will be required to correlate p53 status with clinical outcomes.

Analysis of p53 Serum Antibodies in Patients With Head and Neck Squamous Cell Carcinoma

JNCI Journal of the National Cancer Institute, 1996

Background: Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life. Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techniques. Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients. Purpose: We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical features. Methods: Serum was collected from each patient at the time of diagnosis. In addition, tumor biopsy specimens were obtained before the initiation of treatment. An enzyme-linked immunosorbent assay was used to detect p53-Abs. The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy. Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier method; survival comparisons were made by use of the logrank statistic. Univariate and multivariate analyses were conducted