Epidermal Growth Factor Receptor Immunoexpression Research Articles

Patho-morphological and Immunohistochemical Studies on Bovine Horn Core Carcinoma

Background: An investigation was carried out on twelve clinical cases of neoplasm of horn in Durg, Dhamtari and Rajnandgaon districts of Chhattisgarh, suspected of bovine horn core carcinoma (squamous cell carcinoma) revealed the cytology, pathomorphology and immunohistochemical (IHC) expression of Pan-cytokeratin (Pan- CK), p53 gene, epidermal growth factor receptor (EGFR) and p16 gene in tumourous growth at horn in bovines. Methods: In this field-laboratory investigation conducted during January to June 2022, we explicate the cytological, pathological and immunohistochemical alterations in bovine horn core carcinoma from 12 tissue samples. Cytological studies includes special papaniculaou staining and immunohistochemistry was performed through Benchmark automated staining system. Result: Eight out of 12 cases (66.66%) were confirmed as SCC of horn on the basis of histopathological and immunohistochemical analysis. Papanicolaou staining revealed variation in shape and size of cells and altered nuclear details. Grossly unilateral large cauliflower like neoplastic growth at the base of the horn was observed. Differentiation of tumours were based on histopathology and Immunohistochemistry. Well differentiated SCCs (n=4; 50%) were characterized by severe keratinization of horn epithelium with concentric arrangement forming keratin pearls also called as “cell nests”. Moderately differentiated SCCs (n=2; 25%) characterized by small keratin pearl formations and mitotic figures. Poorly differentiated SCCs of horn (n=2; 25%) revealed absence of distinctive keratin pearls although deep invasion from primary site was observed. Tissue samples revealed strong immunohistochemical staining of Pan-CK, p53 and EGFR and negative to p16. Highest immunohistochemical expression was observed in Pan-CK which confirmed the tumours were of epithelial origin and EGFR immunoexpression was confirmatory for malignancy and degree of metastasis.

Evaluation of EGFR in prognostic characterization in histopathological variants of oral squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of the Erb B family contributing to proliferation, invasion, and metastasis. EGFR overexpression is frequently associated with poor clinical outcome in malignant neoplasms.• To evaluate and compare immunoexpression of EGFR in histopathological variants of oral squamous cell carcinoma (OSCC).• To hypothesize the role of EGFR in determining biological behavior and prognostic course of histopathological variants of OSCC. The study comprised a total of 40 cases including 10 cases each of Squamous cell carcinoma, Verrucous carcinoma, Adenosquamous cell carcinoma, and Adenoid squamous cell carcinoma. EGFR immunoexpression was observed qualitatively as low (1), moderate (2) and strong (3) and quantitatively as score 1 for <10%, 2 for 10%-50%, and 3 for >50% positive cells. The resulting data were analyzed using SPSS software version 19. Data have been expressed as mean and standard deviation. Differences between the different variables were analyzed using ANOVA, and Pearson's Chi-square. (p ≤ 0.05). The study results revealed that the EFGR immunoexpression was highest in adenosquamous cell carcinoma followed by adenoid squamous cell carcinoma then conventional squamous cell carcinoma followed by lowest immunoexpression in verrucous carcinoma. The results were statistically significant. (p ≤ 0.05). Expression of EGFR could be established as a valuable biomarker with significant association in predicting aggressive potential and treatment response in various histopathological variants of OSCC. Further studies where EGFR could be linked to predictive indicators and tumor prognosis could be undertaken.

The immunoexpression of epidermal growth factor receptor in cutaneous squamous cell carcinoma.

Although cutaneous squamous cell carcinomas (cSCCs) account for only 20–25% of non-melanoma skin cancers (NMSCs), they are responsible for most deaths attributable to NMSCs. Apart from SCC seric level, which increases in late-stage disease, no other predictive biomarker for cSCC exists. Epidermal growth factor receptor (EGFR) serves as a predictive biomarker and therapeutic target in numerous malignancies. EGFR immunoexpression is highly elevated in head and neck mucosal SCC. However, its immunoexpression pattern, its relationship with prognosis and survival, and the effect of EGFR targeted therapy in advanced cSCC have not been clarified. We assessed EGFR immunoexpression in 18 cases of cSCC and correlated our findings with the clinicopathological features. Immunohistochemical stainings with anti-EGFR monoclonal antibodies were practiced and the membrane and cytoplasmic immunostaining intensity and quality in the tumors and the non-lesional epithelium were analyzed. Membrane EGFR immunoexpression within the tumors increased with the tumor grade. EGFR overexpression was more frequently found in head and neck cSCCs. We did not find a direct relationship between cytoplasmic EGFR immunoexpression and clinicopathological findings and prognosis. Our results confirm that increased EGFR immunoexpression correlates with aggressive cSCC phenotypes and underline the need for novel treatments for these patients.

Immunoexpression of Epidermal Growth Factor Receptor (EGFR) in Malignant Surface Epithelial Tumours of Ovary

Ovarian cancer is the deadliest gynaecological cancer and approximately 70% are diagnosed in an advanced stage with 5 years survival rate of only 35%. The aim of this study was to find out the distribution of epidermal growth factor receptor (EGFR) immunoexpression in different histological types and grades of malignant surface epithelial tumours of ovary. A total 54 cases of malignant surface epithelial tumours of ovary from North Okkalapa General and Teaching Hospital and Thingangyun Sanpya General Hospital from August 2015 to September 2016 were included. This study included 30 cases (56%) of serous tumour, 18 cases (33%) mucinous tumour, 5 cases (9%) clear cell tumour and one case (2%) of malignant Brenner tumour. Of the 54 cases, 11 cases (20%) were well differentiated, 33 cases (61%) moderately differentiated and 10 cases (19%) poorly differentiated tumours. Different histological types and grades of malignant surface epithelial ovarian tumours were determined for EGFR immunoexpression by peroxidase antiperoxidase method. Out of 54 cases, 31 cases (57.4%) were found to be positive for EGFR immunoexpression and 23 cases (42.6%) showed negative immunoexpression. Among 31 positive cases of EGFR, 54.8% were serous, 32.3% mucinous, 9.7% clear cell and 3.2% were malignant Brenner tumour. The highest EGFR immunoexpression was found in malignant serous, tumour (54.8%). Regarding the histological grades of the 31 positive cases, EGFR immunoexpression was found 9.7% in well differentiated, 64.5% moderately differentiated and 25.8% in poorly differentiated tumours. Increased EGFR immunoexpression was observed predominantly in higher histological grades of ovarian cancers. Since, high EGFR levels have a negative prognostic role in ovarian cancers, further studies with long-term follow-ups are required to determine the prognosis and management of patients with malignant surface epithelial ovarian tumours.

Immunohistochemical Expression of Epidermal Growth Factor Receptor in Hepatocellular Carcinoma.

Epidermal growth factor receptor (EGFR) signaling plays an important role in various cancers, including hepatocellular carcinoma (HCC). We aimed to evaluate immunoexpression of EGFR in HCC and surrounding non-tumor liver tissue and to correlate it to multiple clinicopathologic data. We analyzed 60 patients with HCC for multiple clinicopathologic characteristics and survival. Presence of the immunosignal and the percentage of positive tumor cells at the whole tumor tissue sample and adjacent cirrhotic liver tissue were semi-quantitatively determined. Nineteen patients (31.67%) were female and 41 (68.33%) were male ranging in age from 31 to 85 years, median 61.88±10.51. Mean survival time for female patients was 8.86±1.76 months, for male 13.03±1.50 months and overall survival was 11.6051±1.19 months. The most patients had: T2 status (41.67%), no enlarged lymph nodes (90%), vascular invasion (63.33%) and well differentiated (43.33%) tumors. EGFR immunoexpression was determined in range from 0% to 100% in both tumor and non-tumor tissue with mean value of 39.58% in tumor and 86.86% in cirrhotic tissue (p<0.00). Higher percent of tumor EGFR positive cells were found in cases with higher T status, higher levels of AFP and poorly differentiated carcinoma, but not significantly. Lower percent of tumor EGFR positive cells were found in patients with vascular invasion and enlarged lymph nodes, but also not significantly. EGFR expression in tumor tissue significantly influenced survival of the patients (p<0.05). The study showed that expression of EGFR in lower percentage of tumor cells was associated to favorable prognosis, making it a potential prognostic marker and therapeutic target.

Immunoexpression of EGFR and EMMPRIN in a series of cases of head and neck squamous cell carcinoma

BackgroundThe epidermal growth factor receptor (EGFR) and the extracellular matrix metalloproteinase inducer (EMMPRIN) have been identified as oncologically important targets. This study aimed to evaluate the immunoexpression of EGFR and EMMPRIN in a series of cases of head and neck squamous cell carcinoma (HNSCC). MethodsForty-five cases of HNSCC were selected for this study and evaluated with anti-EGFR and anti-EMMPRIN antibodies. The percentage of positive cells was determined assessing to the following categories: score 1 (staining in 0–50% of cells), score 2 (staining in 51–75% of cells), and score 3 (staining in >75% of cells). Immunostaining intensity was graded according to the following parameters: score 1 (absent/weak expression) and score 2 (strong expression). ResultsFor EGFR, a predominance of high median scores was observed in cases of both histological grades of malignancy and in different clinical stages (p>0.05). For EMMPRIN, a statistically significant difference was observed between the histological grades of malignancy (p=0.030). Regarding the immunostaining intensity of EMMPRIN, it was observed a predominance of score 1 in cases with stages I/II, whereas most cases with stages III/IV presented score 2 (p=0.032). Considering the anatomical location, most cases of buccal floor presented higher median score of EMMPRIN in comparison with the other sites (p=0.015). ConclusionsThese findings suggest that both proteins are potential targets for cancer therapy and EMMPRIN can be used as a prognostic marker of a more aggressive biological behavior in patients with HNSCC.

High-dose atorvastatin ameliorates the uterine microenvironment in streptozotocin-induced diabetic rats

The aim of this study was to investigate whether atorvastatin can ameliorate the uterine microenvironment in diabetes mellitus. Six non-diabetic (control) and 12 diabetic mature female Sprague–Dawley albino rats were used in this study. Diabetes was induced by intraperitoneal injections of 60 mg/kg streptozotocin, and 10 mg/kg/day of oral atorvastatin was administered for 4 weeks via orogastric tubes. The animals were euthanized, and blood samples were collected via cardiac puncture for biochemical analysis. Bilateral hysterectomy was performed for the histopathologic examination. Endometrial gland degeneration and stromal fibrosis scores concomitant with epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) immunoexpressions were analyzed. The endometrial gland degeneration scores, stromal fibrosis scores and VEGF immunoexpression was significantly lower, and the EGFR immunoexpression was significantly higher in the atorvastatin-treated diabetic rats when compared to the non-treated diabetic group, suggesting that atorvastatin ameliorates the uterine microenvironment in diabetes mellitus.

Quantitative and qualitative analysis of epidermal growth factor receptor expression in pericoronal follicles in predicting proliferative potential

Objective. The odontogenic epithelium in pericoronal follicles (PFs) are known to proliferate to form cysts and tumors. This epithelium is mostly composed of the reduced enamel epithelium (REE) and odontogenic rests (OR). The objective of the present study was to evaluate the epidermal growth factor receptor (EGFR) immunoexpression in these PFs to assess their proliferative potential. Study design. The immunoexpression of EGFR in 30 PFs were assessed by two independent observers for intensity, percentage and the location of the EGFR staining. Results. EGFR immunoexpression was noted in 100% of the follicles. A greater proportion of the follicles showed strong intensity (70%). It was noted that nearly 54% of the follicles demonstrated more than 50% of cells with EGFR immunolabelling. EGFR showed combined cytoplasm and membrane staining (40%) and cytoplasm only staining (37%). The analysis of the REE and OR individually for the above-mentioned parameters did not show statistical significance. Conclusion. The increased intensity and overall positivity of the epithelium in follicles shows that odontogenic epithelium is responsive to EGFR mediated growth factors. The predominant combined staining pattern is suggestive of increased potential for the epithelium to undergo cystic or neoplastic proliferation.

EGFR immunoexpression, RAS immunoexpression and their effects on survival in lung adenocarcinoma cases.

The impacts of epidermal growth factor receptor (EGFR) immunoexpression and RAS immunoexpression on the survival and prognosis of lung adenocarcinoma patients are debated in the literature. Twenty-six patients, who underwent pulmonary resections between 2002 and 2007 in our clinic, and whose pathologic examinations yielded adenocarcinoma, were included in the study. EGFR and RAS expression levels were examined by immunohistochemical methods. The results were compared with the survival, stage of the disease, nodal involvement, lymphovascular invasion, and pleural invasion. Nonparametric bivariate analyses were used for statistical analyses. A significant link between EGFR immunoexpression and survival has been identified while RAS immunoexpression and survival have been proven to be irrelevant. Neither EGFR, nor RAS has displayed a significant link with the stage of the disease, nodal involvement, lymphovascular invasion, or pleural invasion. Positive EGFR immunoexpression affects survival negatively, while RAS immunoexpression has no effect on survival in lung adenocarcinoma patients.

EGFR and microvessel density in canine malignant mammary tumours

The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor which has been shown to have an important role in human breast cancer. Its role appears to be associated with increased angiogenesis and metastasis. In order to clarify its role in canine mammary tumours (CMT), 61 malignant neoplasms were studied by using immunohistochemistry, comparing expression of EGFR, microvessel density (MVD) by CD31 immunolabelling and characteristics of tumour aggressiveness. High EGFR immunoexpression was statistically significantly associated with tumour size, tumour necrosis, mitotic grade, histological grade of malignancy and clinical stage. High CD31 immunoreactivity was statistically significantly associated with tubule formation, histological grade of malignancy and clinical stage. A positive correlation between EGFR and CD31 immunoexpression (r=0.843; P<0.001) was also observed. Results suggest that an over-expression of EGFR may contribute to increased angiogenesis and aggression in malignant CMT, presenting the possibility of using EGFR inhibitors in the context of metastatic disease treatment.

Immunohistochemical expression of the epidermal growth factor receptor (EGFR) in colorectal carcinoma: relation with clinicopathological parameters

AbStrACt: Introduction: the study of tissue immunostaining of the epidermal growth factor receptor (eGFr) may contribute with the understanding of its role in the prognosis of colorectal carcinoma. Objective: to analyze the immunohistochemical expression of eGFr in colorectal carcinoma tissues and transitional tumor-mucosa and mucosa adjacent to neoplasia, and its relation with cancer. method: the study was conducted with 40 patients with colorectal carcinoma who had surgery with curative intent in order to analyze the immunoexpression of eGFr with anti-eGFr. We used parametric and nonparametric tests. results: the immunohistochemical expression of EGFR in tumor samples showed a significant difference as to the level of immunostaining in tissue specimens of transi -tional tumor-mucosa (p=0.01) and the level of immunoreactivity in tissues of the adjacent mucosa (p=0, 04). the immunoexpression of EGFR showed no significant relation with the size of the tumor, angiolymphatic invasion, neural invasion, cellular differentiation, level of carcinoma infiltration in the intestinal wall, lymph node metastases and liver metastases. Conclusions: The EGFR showed a more

EGFR Nuclear Import in Gallbladder Carcinoma: Nuclear Phosphorylated EGFR Upregulates iNOS Expression and Confers Independent Prognostic Impact

The understanding of epidermal growth factor receptor (EGFR) deregulation in carcinogenesis remains incomplete. We investigated the implications of EGFR gene status and EGFR nuclear translocation in gallbladder carcinoma (GBCA). Subcellular localization of EGFR and phosphorylated EGFR (pEGFR) was analyzed by fractional immunoblotting and confocal immunofluorescence in GBCA cell lines. pEGFR binding to iNOS promoter was assessed by chromatin immunoprecipitation with iNOS promoter activity evaluated by luciferase assay. EGFR, pEGFR, and iNOS were immunohistochemically assessable for localization and level in the training set of 104 GBCAs on tissue microarrays, with 76 cases analyzed for EGFR gene by chromogenic in situ hybridization (CISH) and mutant-enriched PCR targeting exons 19 and 21. The prognostic impact of nuclear pEGFR (N-pEGFR) immunoexpression was reaffirmed on whole sections of 58 GBCAs in the test set. Nuclear expression of EGFR and pEGFR was substantiated in vitro with augmented activity of iNOS promoter elicited by pEGFR binding upon EGF treatment. Despite no mutation, EGFR amplification, identified in 11 cases (15%) by CISH, strongly correlated with cytoplasmic EGFR expression (P < 0.001) but not with disease-specific survival (DSS). Immunoexpression of nuclear EGFR (N-EGFR), cytoplasmic pEGFR, and N-pEGFR was strongly related to that of iNOS (all ≤0.005). N-pEGFR independently predicted worse DSS in both training (P = 0.0468, HR = 2.024) and test sets (P = 0.0223, HR = 5.573). N-EGFR and N-pEGFR express in GBCA, conferring clinical aggressiveness partly through iNOS transactivation. Lacking response-predicting mutation, EGFR gene status, albeit amplified in 15% of GBCA, is neither related to nuclear EGFR translocation nor prognostically useful.

Impact of EGFR immunoexpression on STAT3 activation and association with proinflammatory/regulatory cytokine pattern in laryngeal squamous cell carcinoma

Stimulation of epidermal growth factor receptor (EGFR) results in the activation of signal transducer and activator of transcription-3 (STAT3), a transcriptional factor associated with carcinogenesis. Proinflammatory cytokines are capable of activating a tumor cell death program by reducing EGFR tyrosine phosphorylation. This study aimed to identify EGFR expression in laryngeal carcinoma and determine the relationship with STAT3 and proinflammatory/regulatory cytokine secretion. An analysis of EGFR expression (membranous EGFR-m and cytoplasmic EGFR-c) was performed in tumor tissues by immunohistochemical (IHC) staining in 45 medical cases of laryngeal carcinoma. STAT3 expression in freshly isolated tumor and non-cancerous normal epithelial cells by RT-PCR was analyzed in 24 patients after total larynx resection. The concentrations of TNFalpha, IL-2, IL-6, IL-8 and IFNgamma secreted by purified peripheral blood mononuclear cells (PBMCs) or contained in whole blood samples were measured by ELISA. The relationship between EGFR and mRNA STAT3 expression as well as the level of secreted cytokines was investigated. In our study, 93.3% tumors expressed EGFR-m and 37.8% EGFR-c. It also revealed a statistically significant dependence of the EGFR status on STAT3 expression in neoplastic tissues. Tumors with IHC EGFR-m positive staining >50% of the total number of cells, as well as with EGFR-c positive staining, were characterized by the most frequent presence of STAT3 expression. Our data demonstrate a significant negative relationship between EGFR-m expression and TNFalpha concentration, and a positive connection between membranous EGFR and IL-8 or IFNgamma levels recorded in isolated PBMCs. Furthermore, this study revealed a significant relationship between EGFR-c immunoexpression and IL-8 or IFNgamma concentration. Our findings have confirmed a key role of EGFR in determining the proliferative and malignant potential of laryngeal carcinoma.

Epidermal Growth Factor Receptor Expression in Serous Ovarian Carcinoma: An Immunohistochemical Study With Galectin-3 and Cyclin D1 and Outcome

This study investigated the expression of epidermal growth factor receptor (EGFR), galectin-3 and cyclin D1 in a cohort of ovarian serous carcinomas with regard to outcome and clinicopathologic parameters. Formalin-fixed paraffin-embedded archival tissues of fifty ovarian serous carcinomas were stained with anti-bodies to EGFR, Gal-3, and cyclin D1 by automated immunohistochemistry. Additionally, 10 benign serous cystadenomas and 10 typical serous borderline ovarian tumors were included in the study. Immunostaining was scored with regard to quantity and intensity of positively stained nuclei. Staining patterns were recorded. The EGFR expression was scored negative in all serous cystadenomas and serous borderline ovarian tumors. Membranous and cytoplasmic EGFR immunoreactivity was determined in 64% of ovarian serous carcinomas; it was related to high grade (P=0.0005) and poor outcome (P=0.0137) but not with stage (P=0.5118). Galectin-3 and cyclin D1 immunostaining decreased from serous cystadenomas and serous borderline ovarian tumors to the carcinomas significantly (P=0.0022 and P=0.0083, respectively). Galectin-3 immunostaining of any pattern (nuclear and cytoplasmic as well as merely cytoplasmic taken together) was not related to grade or stage in cancers; mere cytoplasmic expression was associated with poor outcome (P=0.0097). Cyclin D1 immunoreactivity in predominantly nuclear pattern was increased in low-grade carcinomas (P=0.0378) but was not related to stage and outcome (P=0.6578 and P=0.0675, respectively). This study indicates that with regard to EGFR and cytoplasmic galectin-3 immunoexpression, multiple marker testing may be an adjunct in the identification of high-risk ovarian serous cancers.

Prognostic value of tumour associated antigen immunoreactivity and apoptosis in cerebral glioblastomas: an analysis of 168 cases.

AIMS: To evaluate a possible association between clinical outcome in patients with glioblastoma and expression of some immunohistochemical variables and apoptosis. METHODS: 168 selected patients with cerebral glioblastomas were studied...