Epidermal Growth Factor Receptor Staining Intensity Research Articles

Role of Epidermal Growth Factor Receptor in Gallbladder Carcinoma and its Association with Various Clinicopathological Parameters: A Cross-sectional Study

Introduction: Carcinoma of gallbladder is an aggressive disease with poor outcome. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor that regulate growth, proliferation and differentiation in cells. Increased EGFR receptor expression has been studied in various cancers like lung, colorectal, breast and pancreatic tumours and antiEGFR antibody has been used successfully for therapeutic and diagnostic purposes. Aim: To evaluate EGFR expression in gallbladder carcinoma and its association with clinicopathological factors to reveal its relation to prognosis. Methods and Methods: The present study was a crosssectional study in which 64 samples were collected of resected specimen of Gallbladder Carcinoma (GBC), from the Department of Pathology, King George’s Medical University, Lucknow, Uttar Pradesh, India, for a period of one year and six months. Haematoxylin-eosin-stained sections were evaluated for tumour type and histopathological grading and TNM staging was done. Immunohistochemistry (IHC) was performed and analysed prospectively using ready to use anti-EGFR as per manufacturer’s protocols. Association between EGFR expression and clinicopathological factors were statistically analysed using Statistical Package for the Social Sciences (SPSS) software version 21.0. Results: EGFR expression was positive in 81.25% (52/64) cases of GBC which showed a highly significant association between tumour grade and stage. About 60% of poorly differentiated GBC displayed strong (3+) staining intensity as compared to 30% of moderately differentiated (3+) and 10% of well differentiated tumours (3+). It suggests that with decreasing differentiation of tumour EGFR staining intensity increases (p<0.001). Positivity rate of EGFR expression were also increased with increase of tumour TNM stage (stage I to stage IV). Strong EGFR expression was associated with decreased overall survival with significant p value (p=0.031, log rank test). Conclusion: EGFR expression is inversely related with tumour differentiation, and overall survival. EGFR expression increases with high TNM staging. So, it can be used as prognostic marker for gallbladder carcinoma and opening a hope towards the new therapeutic options

EGFR cut-off point for prognostic impact in laryngeal squamous cell carcinoma

Background: Various molecular biomarkers, including epidermal growth factor receptor (EGFR), have gained importance as predictors of head and neck cancer disease progression.Aims: This study aimed to investigate the ability of EGFR expression as a prognostic marker for laryngeal squamous cell carcinoma (LSCC).Materials and methods: A total of 31 patients with LSCC with immunohistochemistry (IHC) staining for EGFR were examined. Digital image processing was applied to analyze EGFR staining intensity and percent distribution, which were calculated as the H-score. We used a receiver operating characteristic (ROC) curve to identify the best cut-off point of EGFR expression, with H-score separated into high- and low-grade for cancer recurrence prediction.Results: The cut-off point of EGFR expression for high- and low-grades was an H-score of 170 with a sensitivity of 75% and a specificity of 66.7%. Using this cut-off, 14 (45.16%) and 17 (54.84%) patients were categorized as having high- and low-grades EGFR, respectively. The analysis showed a significant reverse correlation between the EGFR grade and LSCC recurrence (RR, 0.4; 95% CI, 0.17–0.98; p = .02).Conclusions: Our study demonstrated that EGFR grading using H-score with the generated cut-off point by the ROC curve might be further applied as a potential marker for LSCC prognostic prediction.

P4.08 - Expression of Epidermal Growth Factor Receptor in Human Endometrial Hyperplasia and Carcinoma

ABSTRACT According to researches, there are many discordant data about the prognostic significance of epidermal growth factor receptor in endometrium. The intensity of Epidermal Growth Factor Receptor (EGFR) expression in human endometrial hyperplasia and carcinoma was the focus of our study. 45 patients have been investigated clinically and morphologically. Of them, 27 patients of reproductive age, 8 patients of gestational age and 10 patients of postmenopausal period. Clinical examination revealed endometrial hyperplasia manifested by metrorrhagia in 35 (27 + 8) patients. For morphological study the material was collected by endometrial scrap. Histological and immunohistochemical studies were performed as well. The numeric data obtained were processed statistically using the SPSS-12 program. Based on the results, expression of epidermal growth factor receptor was diagnosed in 100% of the patients. Of them, mild EGFR expression was documented in 42.2% (p 0.1). In complex endometrial hyperplasia with atypia (only one case of atypical hyperplasia), EGFR was revealed with high intensity. The results of the study suggest that in complex hyperplasia mild EGFR expression predominates, while sharp EGFR expression is mostly typical of complex hyperplasia. At the same time, EGFR staining intensity increases with the severity of hyperplasia. With endometrial carcinoma (endometrioid carcinoma, adenocarcinoma), a drastic intensity of EGFR expression is observed.

Cetuximab in advanced non-small cell lung cancer (NSCLC): the showdown?

Cetuximab in advanced non-small cell lung cancer (NSCLC): the showdown?

Expression of epidermal growth factor receptor and human epidermal growth factor receptor 2 in periocular squamous cell carcinomas of horses.

To determine whether epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are expressed in periocular squamous cell carcinomas (SCCs) of horses. Biopsy specimens of SCCs from 46 horses. Pathology records were searched retrospectively for biopsy specimens of periocular SCCs obtained from horses. Slides of the specimens were reviewed histologically to confirm the SCC diagnosis and stained for EGFR and HER2 by immunohistochemical methods. For both EGFR and HER2, the immunohistochemical staining intensity and percentage of stain-positive cells on the slides were determined. 43 of 46 (93%) SCCs were immunoreactive for EGFR. The median score for EGFR staining intensity was 4 (range, 2 to 12), and the median number of mitotic figures was 8 mitotic figures/10 hpfs (range, 0 to 34 mitotic figures/10 hpfs). Mitotic index was not correlated with the percentage of EGFR stain-positive cells or staining intensity. Of the 43 EGFR-immunoreactive SCCs, 38 had stain present primarily in the cytoplasm and 5 had stain equally distributed between the cytoplasm and cell membranes. Thirty-five of 46 (76%) SCCs were immunoreactive for HER2. Mitotic index was not correlated with the percentage of HER2 stain-positive cells or staining intensity. Of the 35 HER2-immunoreactive SCCs, the stain was present primarily in the cytoplasm and 7 had stain equally distributed between the cytoplasm and cell membranes. Results indicated that most periocular SCCs of horses expressed EGFR and HER2, which suggested that equine periocular SCCs might respond to treatment with EGFR inhibitors.

Prognostic Significance of Human Papillomavirus (HPV) Status and Expression of Selected Markers (HER2/neu, EGFR, VEGF, CD34, p63, p53 and Ki67/MIB-1) on Outcome After (Chemo-) Radiotherapy in Patients with Squamous Cell Carcinoma of Uterine Cervix

The aim of the retrospective study was to evaluate prognostic significance of human papillomavirus (HPV) status and expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2/neu), vascular endothelial growth factor (VEGF), CD34 antigen, tumor suppressors p63 and p53, and Ki67/MIB-1 in squamous cell carcinoma of the uterine cervix (SCCC) treated with radiotherapy or chemoradiotherapy. Seventy-two consecutive patients with SCCC, diagnosed and treated with (chemo-) radiotherapy with a curative intent at the University Hospital Hradec Kralove between August 1998 and August 2008, were enrolled in the study. The median follow-up period was 57months (range 5-152). The tested biological factors were evaluated by polymerase chain reaction (HPV status) and by immunohistochemistry (remaining above mentioned markers) from archival paraffin embedded original diagnostic tumor samples. A statistical significant correlation was observed between low expression of p63 and poor overall survival (p = 0.001), although the complete response probability was influenced with borderline statistical significance (p = 0.05). However, the results could be affected by the statistical error due to the small number of p63 negative patients. HPV positivity and EGFR staining intensity was associated with higher complete response probability (p = 0.038 and p = 0.044, resp.). All other results were not significant. Neither HPV positivity nor EGFR staining intensity were reflected in the overall survival evaluation. In conclusion, the presented study did not confirm any apparently significant association of the suggested markers with prognosis of SCCC in patients treated with (chemo-) radiotherapy.

Epidermal Growth Factor Receptor Expression As Prognostic Marker in Patients With Anal Carcinoma Treated With Concurrent Chemoradiation Therapy

To investigate the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment tumor biopsy specimens of patients with anal cancer treated with concurrent 5-fluorouracil and mitomycin C-based chemoradiation therapy (CRT). Immunohistochemical staining for EGFR was performed in pretreatment biopsy specimens of 103 patients with anal carcinoma. EGFR expression was correlated with clinical and histopathologic characteristics and with clinical endpoints, including local failure-free survival (LFFS), colostomy-free survival (CFS), distant metastases-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). EGFR staining intensity was absent in 3%, weak in 23%, intermediate in 36% and intense in 38% of the patients. In univariate analysis, the level of EGFR staining was significantly correlated with CSS (absent/weak vs intermediate/intense expression: 5-year CSS, 70% vs 86%, P=.03). As a trend, this was also observed for DMFS (70% vs 86%, P=.06) and LFFS (70% vs 87%, P=.16). In multivariate analysis, N stage, tumor differentiation, and patients' sex were independent prognostic factors for CSS, whereas EGFR expression only reached borderline significance (hazard ratio 2.75; P=.08). Our results suggest that elevated levels of pretreatment EGFR expression could be correlated with favorable clinical outcome in anal cancer patients treated with CRT. Further studies are warranted to elucidate how EGFR is involved in the response to CRT.

SELECT: Randomized phase III study of docetaxel (D) or pemetrexed (P) with or without cetuximab (C) in recurrent or progressive non-small cell lung cancer (NSCLC) after platinum-based therapy.

7502 Background: SELECT investigated whether the addition of C to standard chemotherapy improved progression-free survival (PFS) in patients (pts) with recurrent or progressive NSCLC after failure of platinum-based therapy. Methods: SELECT was a multicenter, open label, randomized phase III trial. Per investigator choice, pts received either P (500 mg/m2) or D (75 mg/m2) on day 1 and then were randomized within each group to chemotherapy plus C (400/250 mg/m2) (initial/weekly) or chemotherapy alone. Therapy was given for up to six 3-week cycles; pts randomized to C continued weekly monotherapy until disease progression or unacceptable toxicity. The primary objective was PFS for PC vs. P as determined by an Independent Review Committee (IRC). Secondary endpoints included overall survival (OS), objective response rate (ORR) and duration of response (DOR) by IRC, and safety. Preplanned subgroup analyses for epidermal growth factor receptor (EGFR) staining intensity by immunohistochemistry and histology were performed. Results for PC vs. P only are presented. Results: Between Jan 2005 and Feb 2010, 938 total pts were randomized. Baseline demographics were comparable between PC (n=301) and P (n=304): median age 64 years; male 60%; Caucasian 88%; KPS 80-100/60-70 84%/16%; squamous/non-squamous 24%/76%. Median PFS (months) PC: 2.89 and P: 2.76 (hazard ratio [HR] =1.03 [95% confidence interval (CI)=0.87-1.21]; p=0.76). Median OS (months) PC: 6.93 and P: 7.79 (HR=1.01 [95% CI=0.86-1.20]; p=0.86). ORR PC: 6.6% and P: 4.3% (odds ratio =1.59 [95% CI=0.78-3.26]; p=0.20). Median DOR (months) PC: 4.17 and P: 6.93 (HR=1.58 [95% CI=0.74-3.36]; p=0.24). There were no statistical differences in efficacy based on histology or EGFR staining intensity. More drug-related AEs/SAEs were observed in the PC arm, with differences mainly attributable to skin toxicities, GI (diarrhea/stomatitis), and hypomagnesemia. Conclusions: The addition of C to P did not improve efficacy in this pt population. Further biomarker analyses are planned. The safety profiles for C and P were consistent with existing data and no new safety signals were observed.

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

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.

Expression modes and clinical manifestations of latent membrane protein 1, Ki‐67, cyclin‐B1, and epidermal growth factor receptor in nonendemic nasopharyngeal carcinoma

We aimed to identify clinical significance of latent membrane protein 1 (LMP1), Ki-67, cyclin-B1, and epidermal growth factor receptor (EGFR), in nonendemic nasopharyngeal carcinoma (NPC). The relation between expression of the markers in 45 NPC specimens and clinicopathological and survival variables was statistically analyzed. LMP1 was present in 33% of the tumors, and its presence was associated with advanced nodal and disease stages. Overexpression was defined as labeling index > or = median value for Ki-67, > or = 15% for cyclin-B1, and > or =50% for EGFR, and it was displayed in 50%, 55%, and 80% of the specimens, respectively. Strong EGFR staining intensity and not overexpression of the 3 markers was the variable with statistically significant impact on treatment outcomes in terms of worse local and locoregional tumor control rates. Our results suggest that the evaluation of EGFR staining intensity in patients with NPC may identify a subgroup of patients with poor prognosis.

Epidermal growth factor receptor expression in pre-invasive and early invasive bronchial lesions

The 1999 World Health Organization/International Association for the Study of Lung Cancer histological classification of preneoplastic bronchial lesions has been shown to be reproducible but little is known about its biological significance. The current study evaluated the correspondence between the morphological changes of the bronchial epithelium and epidermal growth factor receptor (EGF-R) expression. Thirteen normal bronchial epithelia, 19 hyperplasia, 16 metaplasia, 10 mild dysplasia, one moderate dysplasia, 10 severe dysplasia (SD), 14 carcinoma in situ (CIS) and 11 microinvasive tumours were assessed. A global EGF-R score obtained by the sum of the positivity score plus the EGF-R staining intensity score was calculated for each lesion. A global EGF-R score of >5 was reached only in one metaplasia, in six SD, in six CIS and in six microinvasive tumours. There was no difference in EGF-R expression between normal, hyperplastic and metaplastic epithelia versus mild dysplasia or between severe dysplasia versus CIS and microinvasive tumours but there was a statistically significant difference between mild versus severe dysplasia. This study demonstrates that epidermal growth factor receptor expression rate changes with the stage of the bronchial lesion, increasing from normal epithelium to carcinoma in situ and microinvasive tumours with a statistically significant difference between mild versus severe dysplasia.

In situ evaluation of the relationship between epidermal-growth-factor-receptor status and tumor-cell proliferation in colon carcinomas.

The association between the expression of the epidermal-growth-factor receptor (EGFR) and tumor proliferation was studied in 69 resected human adenocarcinomas of the colon. EGFR was detected immunohistochemically using the monoclonal antibody (MAb) EGFRI. Tumor-cell proliferation was assessed with the MAb Ki-67 directed against a proliferation-associated nuclear antigen expressed only in proliferating cells. The percentage of Ki-67-positive tumor cells (Ki-67 index) was evaluated by the point-counting method. Forty-seven carcinomas contained detectable EGFR immunoreactivity. Statistical analysis failed to reveal correlations between the EGFR status and T, N and M stages or tumor differentiation. The mean Ki-67 index did not differ between EGFR-positive and -negative carcinomas. Seven tumors contained clearly distinguishable areas with different EGFR staining intensity. In these tumors with a locally heterogeneous EGFR expression, tumor proliferation also did not correlate with EGFR immunoreactivity. These in situ observations suggest that EGFR expression may not play an important role in the growth regulation of human colonic carcinomas.