Immunohistochemical expression of epidermal growth factor receptor (EGFR) in oral squamous cell carcinoma in relation to proliferation, apoptosis, angiogenesis and lymphangiogenesis (original) (raw)

Immunohistochemical and FISH analysis of EGFR and its prognostic value in patients with oral squamous cell carcinoma

Journal of Oral Pathology & Medicine, 2013

OBJECTIVES: To study immunohistochemical expression of the epithelial growth factor receptor (EGFR) in oral carcinomas and the head and neck region to examine possible associations with various features of the tumors and survival of the patients. MATERIALS AND METHODS: Sections were made from two tissue arrays composed of 206 oral squamous cell carcinomas and 427 squamous cell carcinomas of the head and neck region, respectively, and examined for EGFR expression and Ki-67 labeling index by means of immunohistochemistry, and for EGFR gene amplification by means of fluorescence in situ hybridization. Correlation between resulting parameters and with clinical features was evaluated using chi-square test and Kaplan-Meyer analysis. RESULTS: A statistically significant association was observed for strong EGFR immunohistochemical (IHC) expression with advanced lymph node involvement (P = 0.02). EGFR immunohistochemical expression did not significantly correlate with patient disease specific (DS) or overall survival (OS). EGFR gene amplification was not correlated with any of the tumor features nor to survival of the patients (DS and OS). DISCUSSION: Epithelial growth factor receptor IHC expression and gene amplification might be suitable to predict locoregional control in oral squamous cell carcinoma patients but an inappropriate predictor for patients survival.

Immunohistochemical Expression of Epidermal Growth Factor Receptor among Metastatic and Nonmetastatic Oral Squamous Cell Carcinomas

World Journal of Dentistry , 2019

Aim: To evaluate and correlate the epidermal growth factor receptor (EGFR) expression in oral squamous cell carcinomas (OSCC) patients with metastasis and without metastasis. Materials and methods: The study comprised of 40 samples, 20 cases of metastatic and 20 nonmetastatic OSCC. All the cases were immunostained for EGFR antibody. Epidermal growth factor receptor stained sections were evaluated for staining intensity and distribution. The differences between the groups were statistically analyzed using Chi-square test. Results: Immunoexpression of EGFR in OSCC was 100% among the study groups, where metastatic group showed an increased positive expression comparing to nonmetastatic OSCC that show statistically significance among the study groups. Conclusion: Expression of EGFR can be used as reliable biomarker for prognosis which can be employed in the prediction of the survival of the patient with OSCC. Clinical significance: Since we are in the theragnostic era, evaluating and quantifying the expression of EGFR in OSCC patient will definitely pave a way in targeted drug therapy and personalized medicine for the diseased.

Immunoscoring of epidermal growth factor receptor expression in recurrent cases of oral squamous cell carcinoma

Journal of Oral Pathology & Medicine, 2015

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a genetic disease with high prevalence and poor survival. Evaluation of recurrent tumor for a valid biomarker may serve as a predictive system for analyzing prognostic course of this disease. This study was designed to evaluate and compare the immunoscoring of epidermal growth factor receptor (EGFR) expression in recurrent cases with their matched regional/locoregional recurrence and non-recurrent cases of OSCC. METHODOLOGY: A total of 64 cases of OSCC were studied and immunostained with polyclonal EGFR antibody. Of these, 33 cases recurred at the end of 5 years of follow-up. For positive evaluation of EGFR staining, immunscoring was performed by adding the extent score and intensity score. RESULTS: We observed significant increase in EGFR immunoscore in recurrent cases of OSCC (P-value 0.001). Immunoscoring of EGFR expression is an independent prognostic and/or predictive parameter for recurrence in OSCC (Odds Ratio: 6.52). CONCLUSION: Immunoscore using EGFR can be incorporated into traditional classification, thus providing an essential prognostic and potentially predictive tool.

Expression and clinical significance of the receptors of the EGF family in oral squamous cell carcinomas

Objective: To examine the immunohistochemical expression of four members of the type 1 growth factor receptor family in oral squamous cell carcinomas (OSCCs) and to correlate with clinical outcomes. Materials and methods: Sixty OSCCs from a patient cohort in Sri Lanka were included in the study. Five sections from each carcinoma were immunostained with antibodies to epidermal growth factor receptor (EGFR)/c-erbB-1, c-erbB-2/HER-2/neu, c-erbB-3/HER-3 and c-erbB-4/HER-4. Two clones were used to stain for c-erbB-2/HER-2/neu. Semiquantitative analysis of immunoreactivity was carried out by scoring the intensity of expression and proportions of positively stained cells. A logistic regression analysis was performed to examine positive expression against overall survival. Results: There was heterogenous expression of the four receptors, positivity ranging from 26% to 60%. Co-expression of all four markers was observed only in 1-3% of the tumours. Both membranous and cytoplasmic expressions were observed, EGFR showing predominantly membranous expression and c-erbB-2 showing only cytoplasmic staining. In logistic regression analysis, none of the growth factor receptors were significantly predictive of overall survival. Conclusion: Type 1 growth factor receptors are highly expressed in oral carcinomas, EGFR being the predominant marker.

Evaluation Of Transforming Growth Factor (Tgf- ) And Epidermal Growth Factor Receptor (Egfr) Expression In Oral Squamous Cell Carcinoma

The Egyptian Journal of Hospital Medicine

Objective: The present study aimed to investigate the pattern of expression of transforming growth factor & (TGF-&) and epidermal growth factor receptor (EGFR) in oral squamous cell carcinoma (OSCC) and to correlate their expression with tumor grading. Methods: ' (') *! +#,,))) Results:For both markers, positive staining reaction was characterized by cytoplasmic or cytoplasmic and membranous staining. EGFR was expre-' ./-& ' 0 1!-2)) ' particularly strong at the margin of invading cords and nests of tumour cells and poorly differentiated malignant cells. The expression of both markers was significantly correlated with histological grading; while the staining intensity showed no correlation with tumor grading. Conclusion: This study showed that OSCC express both EGFR and TGF-& and their expression indicated that these markers may have a potential diagnostic value in histologic examination. In addition their increased expression in high tumour grades suggest that they may be used as indicators of tumor aggressiveness.

Nuclear Epidermal Growth Factor Receptor Overexpression as a Survival Predictor in Oral Squamous Cell Carcinoma

International Journal of Molecular Sciences

The aim of this study was to determine, by immunohistochemical methods, the expression of nEGFR and markers of cell proliferation (Ki-67), cell cycle (mEGFR, p53, cyclin D1), and tumor stem cells (ABCG2) in 59 pathohistological samples of healthy oral mucosa, 50 oral premalignant changes (leukoplakia and erythroplakia), and 52 oral squamous cell carcinomas (OSCC). An increase in the expression of mEGFR and nEGFR was found with the development of the disease (p < 0.0001). In the group of patients with leukoplakia and erythroplakia, we found a positive correlation between nEGFR and Ki67, p53, cyclin D1, and mEGFR, whereas in the group of patients with OSCC, we found a positive correlation between nEGFR and Ki67, mEGFR (p < 0.05). Tumors without perineural (PNI) invasion had a higher expression of p53 protein than tumors with PNI (p = 0.02). Patients with OSCC and overexpression of nEGFR had shorter overall survival (p = 0.004). The results of this study suggest a potentially imp...

EGFR protein overexpression and gene copy number increases in oral tongue squamous cell carcinoma

European Journal of Cancer, 2009

New promising therapeutic agents targeting epidermal growth factor receptor (EGFR) have been developed although clinical information concerning EGFR status in oral tongue squamous cell carcinoma (OTSCC) is limited. We investigated EGFR protein expression and gene copy numbers in 78 pretreatment OTSCC paraffin samples. EGFR protein expression was found in all 78 tumours, of which 72% showed an intense staining. Fifty-four percent of the tumours had high (≥four gene copies) EGFR gene copy numbers. EGFR gene copy number was significantly associated with EGFR protein expression (P = 0.002). Pretreatment EGFR staining intensity tended to be associated with non-pathological complete remission after preoperative radiotherapy for Stage II OTSCC. No correlation was found between EGFR status and survival. EGFR FISH results were significantly (P = 0.003) higher in more advanced tumours (Stages II, III and IV) than in the tumours in Stage I. Non-smokers exhibited a significantly higher EGFR gene copy number and protein overexpression in Stages I and II OTSCC than smokers (P = 0.001, P = 0.009). In conclusion, EGFR was found to be overexpressed in all OTSCCs making this cancer type interesting for exploring new therapeutic agents targeting the EGFR receptor.

The importance of immunohistochemical expression of EGFr in squamous cell carcinoma of the oral cavity treated with surgery and postoperative radiotherapy

International Journal of Radiation Oncology*Biology*Physics, 2006

Purpose: The aim of this study was to investigate the prognostic significance of epidermal growth factor (EGFr) expression in oral cavity squamous cell carcinoma (OCSCC) treated with curative surgery and postoperative radiotherapy. Methods and Materials: This retrospective study included 165 OCSCC patients. The expression of EGFr was assessed on paraffin-embedded tissue of the primary tumor by immunohistochemistry using a monoclonal antibody directed against EGFr. Intensity of the EGFr expression was scored by two authors blinded for the clinical outcome. Results: In the univariate analysis, locoregional control at 3 years (LRC) in the EGFr-negative cases was 69% compared with 77% in the EGFr-positive cases (p ‫؍‬ 0.22). In the multivariate analysis for local control, a significant interaction was found between EGFr and overall treatment time of radiation (OTT). After stratification for EGFr expression, the OTT was of no importance in the EGFr-negative cases, whereas a significant difference in LRC was found in the EGFr-positive cases, in which the LRC after 3 years was 69% and 94% in case of an OTT of 0 -42 days and >42 days, respectively (p ‫؍‬ 0.009; hazard ratio ‫؍‬ 3.42; 95% confidence interval, 1.28 -8.96). No significant association was found between EGFr expression and overall survival. Conclusions: In the present study, no association was found between EGFr expression and outcome regarding locoregional control and overall survival. However, the results of the present study suggest that patients with squamous cell carcinoma of the oral cavity with high EGFr expression benefit more from a reduction of the overall treatment time of postoperative radiation than those with low EGFr expression.

Changes in Epidermal Growth Factor Receptor Gene Copy Number during Oral Carcinogenesis

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016

Oral squamous cell carcinoma (OSCC) is a global healthcare problem associated with poor clinical outcomes. Early detection is key to improving patient survival. OSCC may be preceded by clinically recognizable lesions, termed oral potentially malignant disorders (OPMD). As histologic assessment of OPMD does not accurately predict their clinical behavior, biomarkers are required to detect cases at risk of malignant transformation. Epidermal growth factor receptor gene copy number (EGFR GCN) is a validated biomarker in lung non-small cell carcinoma. We examined EGFR GCN in OPMD and OSCC to determine its potential as a biomarker in oral carcinogenesis. EGFR GCN was examined by in situ hybridization (ISH) in biopsies from 78 patients with OPMD and 92 patients with early-stage (stages I and II) OSCC. EGFR ISH signals were scored by two pathologists and a category assigned by consensus. The data were correlated with patient demographics and clinical outcomes. OPMD with abnormal EGFR GCN we...

Role of epidermal growth factor receptor expression in recurrent cases of oral squamous cell carcinomas

Background: Oral squamous cell carcinoma (OSCC) is the most common head and neck cancers and locoregional recurrence in OSCC is related to lowest survival rate. The present study was undertaken to compare the clinicopathological findings and epidermal growth factor receptor (EGFR) expression in recurrent and non-recurrent cases of OSCC. Methodology: A total of 64 cases of OSCC were studied and immunohistochemistry was done, of which, 33 cases recurred at end of follow up. Categorical variables for each case included age, gender, site of primary lesion, neck metastasis, AJCC stage, locoregional recurrence, histological grade and pattern of invasion. Results: In quantitative analysis, 7 cases (21.2%) of recurrent OSCC and one case (3.2%) of non recurrent OSCC with EGFR extent score 4 was observed. In qualitative analysis, 5 cases (3.22%) of recurrent group and one case (0.64%) of non recurrent group with strong intensity was observed. Recurrent cases of OSCC showed higher score of EGFR expression [extent {p-value 0.001} and intensity {p-value 0.03}]. However, on clinicopathological correlation of EGFR expression, no significant correlation was observed. In TNM stage IV, out of 22 cases only 7 cases (4.48%) showed recurrence. Among 26 cases, 17 Cases (10.88%) of recurrent OSCC with H/P grade I showed recurrence. Recurrence was frequently observed in 15 cases (9.6%) with pattern of invasion (POI) type II. Conclusion: The EGFR expression in between recurrent and non-recurrent OSCC can be exploited as prognostic /or predictive parameter despite its role as therapeutic marker.