Positive Staining For Epidermal Growth Factor Receptor Research Articles

Investigating the novel CD16A and epidermal growth factor receptor (EGFR) bispecific innate cell engager, AFM24, to leverage the innate immune system: Interim results from the colorectal cancer (CRC) cohort.

e14508 Background: AFM24 is a tetravalent, bispecific innate cell engager that binds EGFR on solid tumors and CD16A on natural killer (NK) cells. AFM24 redirects NK cells to EGFR-expressing (EGFR+) solid tumors, enhancing antibody-dependent cellular cytotoxicity. AFM24 induced lysis of EGFR+ tumor cell lines in vitro independent of EGFR expression level and mutation status. The dose escalation phase (Phase 1) of the presented study (NCT04259450) previously established the recommended Phase 2 dose at 480 mg based on tolerability, receptor occupancy, and pharmacokinetics. Correlative science data revealed an activation and enrichment of immune cells in the tumor microenvironment. Here we present preliminary data from the Phase 2a CRC expansion cohort. Methods: The Phase 2a expansion phase is evaluating 480 mg AFM24 in patients with histologically or cytologically confirmed microsatellite stable, RAS wild type EGFR+ CRC. Patients have relapsed or refractory disease to ≥2 prior lines of therapy including an EGFR targeted therapy. EGFR+ is defined as positive staining for EGFR in ≥1% of tumor cells per local immunohistochemistry assay. The study follows Simon’s two-stage design. The primary endpoint is the overall response rate per RECIST v1.1 by investigator assessment; secondary endpoints include safety and tolerability; efficacy per iRECIST is exploratory. AFM24 is administered intravenously once weekly in a 28-day cycle. Tumor assessments are performed at screening, cycles 2, 4, 6, 8, and every 3 cycles thereafter. Results: As of December 2022, 16 patients with Stage 4 CRC were enrolled and treated with 480 mg AFM24 in the study. The median (range) age was 66 years (51–77); 11 males and 5 females; 9 Asian, 7 White). The median number of prior therapies was 4 (2–7) and the median treatment duration was 5.1 weeks (1.0–22.0). Treatment-related adverse events (TRAEs) were reported in 14/16 patients; infusion-related reactions (IRRs, 12), pruritus (3), lymphopenia (3), and anemia (2) were the most common. AFM24 TRAEs of Grade ≥3 occurred in 6 patients and included lymphopenia (3), decreased neutrophil count (1), increased blood bilirubin (1) and IRRs (1). To date, no objective responses were observed. Seven patients remain on treatment including 1 patient with confirmed stable disease ongoing for 5 months exhibiting a tumor reduction of –17%. Final interim results will be presented. Conclusions: The novel mechanism of action of AFM24 may provide an alternative treatment approach for patients with EGFR+ solid tumors. In this study, AFM24 monotherapy was adequately tolerated in a heavily pretreated population of patients with EGFR+ CRC. AFM24 is also being investigated in combination with atezolizumab and autologous NK cells in various EGFR+ solid tumors. Clinical trial information: NCT04259450 .

Leveraging innate immunity with AFM24, a novel CD16A and epidermal growth factor receptor (EGFR) bispecific innate cell engager: Interim results for the non-small cell lung cancer (NSCLC) cohort.

2533 Background: Patients with EGFR mutant NSCLC who progress on or after small molecule EGFR inhibitors have only limited treatment options. AFM24 is a tetravalent, bispecific innate cell engager that binds EGFR on solid tumor cells and CD16A on NK cells to redirect and enhance antitumor antibody-dependent cellular cytotoxicity, thus acting independently of the EGFR downstream signaling pathway and EGFR expression levels. The Phase 1 dose escalation phase of the presented study (NCT04259450) established the recommended Phase 2 dose of AFM24 monotherapy at 480 mg based on tolerability, receptor occupancy, and pharmacokinetics (PK). Correlative science data revealed an activation and enrichment of immune cells in the tumor microenvironment. Methods: The Phase 2a expansion phase is evaluating 480 mg AFM24 in patients with EGFR mutant NSCLC, relapsed or refractory to ≥1 prior lines of therapy; EGFR-positivity is defined as positive staining for EGFR in ≥1% of tumor cells per local immunohistochemistry assay. The study follows Simon’s two-stage design. The primary endpoint is overall response rate per local RECIST v1.1; secondary endpoints include safety, PK, and immunogenicity. Efficacy per iRECIST is an exploratory endpoint. AFM24 is administered intravenously once weekly in a 28-day cycle. Tumor assessments are performed at initial screening, cycles 2, 4, 6, 8, and every 3 cycles thereafter. Results: As of December 2022, 14 patients (median [range] age 55 [37–82]; 12 male; 11 Asian, 3 White) were enrolled; the median number of prior therapies was 2.5 (1–12). Median treatment duration with AFM24 was 6.7 weeks (1.0–26.1). Best objective response in 10 evaluable patients was confirmed partial response in 1 patient (change from baseline –45%); 4 patients exhibited stable disease, 1 was confirmed. Tumor shrinkage occurred in 2 patients with stable disease (–6%, –18%). The tumor control rate was 50%. Treatment-related adverse events (TRAEs) were reported in 13 patients; infusion related reactions (IRRs, 12), dermatitis acneiform, neutrophil count decreased, decreased appetite, and myalgia (2 each) were most common. Grade ≥3 TRAEs occurred in 4 patients and included decreased neutrophil count (2), lymphopenia, and IRR (1 each). Grade 5 pneumonitis was observed in 1 patient with disease progression and multiple comorbidities; relation to AFM24 could not be ruled out. As of January 2023, enrollment is ongoing; results of the interim analysis will be presented. Conclusions: AFM24 demonstrated clinical activity and acceptable safety in heavily pretreated patients with EGFR mutant NSCLC. The novel mechanism of action of AFM24 could add to the therapeutic options for patients with EGFR expressing tumors and is under clinical evaluation as a single agent and in combination with atezolizumab or autologous NK cells. Clinical trial information: NCT04259450 .

Prognostic Impact of Low-Level p53 Expression on Brain Astrocytomas Immunopositive for Epidermal Growth Factor Receptor.

Although the expression of p53 and epidermal growth factor receptor (EGFR) is associated with therapeutic resistance and patient outcomes in many malignancies, the relationship in astrocytomas is unclear. This study aims to correlate p53 and EGFR expression in brain astrocytomas with overall patient survival. Eighty-two patients with astrocytomas were enrolled in the study. Semi-quantitative p53 and EGFR immunohistochemical staining was measured in tumor specimens. The mean follow-up after astrocytoma surgery was 18.46 months. The overall survival rate was 83%. Survival was reduced in EGFR-positive patients compared with survival in EGFR-negative patients (p < 0.05). However, no significant differences in survival were detected between patients with high and low p53 expression. In patients with low p53 expression, positive EGFR staining was associated with significantly worse survival compared with patients with negative EGFR staining (log-rank test: p < 0.001). Survival rates in positive and negative EGFR groups with high p53 protein expression were similar (log-rank test: p = 0.919). The IC50 of an EGFR inhibitor was higher in GBM cells with high p53 protein expression compared with the IC50 in cells with low p53 expression. Combined EGFR and p53 expression may have prognostic significance in astrocytomas.

Tumor-Associated Macrophages are Correlated with Tamoxifen Resistance in the Postmenopausal Breast Cancer Patients

Tumor-associated macrophages (TAMs) have been correlated with increased angiogenesis and poor prognosis in breast cancer. However, the precise role of TAMs in tamoxifen resistance remains unclear. We used immunohistochemical method to examine the expression of epidermal growth factor receptor (EGFR) and CD163+ macrophages in 100 breast cancer tissues. The clinical and biological features of 100 patients were estrogen receptor (ER)-positive and human epidermal growth factor receptor 2(Her-2)-negative tumors. The tamoxifen resistant tissues (n = 48) were the surgical excision samples from patients who developed recurrence or metastasis at the time of adjuvant tamoxifen treatment. The tamoxifen resistant tissues were contrast to tamoxifen sensitive tissues (n = 52). Positive staining for EGFR and CD163+ macrophages were observed in 21 samples (43.8 %) and in 26 samples (54.2 %) respectively in tamoxifen resistance group, which were higher than that of tamoxifen sensitive group (P = 0.001 and P = 0.000279 respectively). Significant positive correlations were found between the expression of EGFR and CD163+ macrophages (r = 0.567, P < 0.01). CD163+ macrophages were positively correlated with tumor size, lymph node metastasis and obesity. Obesity was also related to tamoxifen resistance (P < 0.05). The patients with higher density of CD163+ macrophages infiltration suffered from shorter time to develop recurrence or metastasis (P < 0.05). TAMs may be associated with tamoxifen resistance. Further studies are needed to investigate the potential mechanism between TAMs and tamoxifen resistance.

Significance of Ki-67 and p53 immunoexpression in the differential diagnosis of oral necrotizing sialometaplasia and squamous cell carcinoma

Necrotizing sialometaplasia (NS) is a benign condition that usually involves the hard palate and can be mistaken for invasive squamous cell carcinoma (SCC). In this study, we have demonstrated that p53 and Ki-67 staining may assist in the differential diagnosis of NS from SCC. Thirteen cases of NS and 20 cases of oral cavity SCC were randomly selected from our surgical pathology archive from 1992 to 2009. Each case was additionally stained with Ki-67, p53, BCL-2, p16, and epidermal growth factor receptor (EGFR) antibodies. All 13 cases of NS were negatively stained for BCL-2, EGFR, and Ki-67. Three cases (23%) showed weak and focal positive nuclear staining for p53. Two cases (15%) showed positive staining for p16. In 16 well-differentiated SCC cases, p53 was positive in 12 cases (75%); BCL-2, p16, EGFR were positive in 3 cases (18%); and Ki-67 was positive in all cases (100%). In 4 moderately differentiated SCC cases, p53 expression was positive in all cases. Two tumors (50%) had a positive expression of BCL-2. Three cases (75%) had a positive p16 staining, and 1 (25%) had a positive EGFR staining. All cases were positive with high nuclear staining greater than 35% of cells for Ki-67. Ki-67 and p53 showed more intense staining and increased in moderately differentiated SCC comparing with well-differentiated SCC and NS. BCL-2, EGFR, and p16 had the same pattern of staining with the same extent in NS and SCCs. The diagnosis of NS may be difficult and may be supplemented via immunohistochemistry by demonstrating focal or absent p53, low to absent Ki-67 (<10% of cells). Although Ki-67 and p53 staining are generally more intense and are increased in malignancy, these findings may be helpful adjuncts in the differential diagnosis of NS from SCC in appropriate clinical setting.

Expression of epidermal growth factor receptor in adult human airway epithelium--application of AMeX method

To elucidate the role of epidermal growth factor (EGF) in the maintenance and repair of airway epithelial cells in adult humans, we investigated immunohistochemically whether EGF receptor (EGFR) is expressed in these cells. In the present study, we employed the AMeX method (Sato et al., 1986) for tissue preparation. We first examined the expression of EGFR in peripheral lung tissue and bronchial tissue obtained at surgery from thirteen adult patients with lung carcinoma. The results showed that there was no positive staining for EGFR in the bronchial surface epithelium, bronchial glandular cells, bronchiolar epithelium or alveolar lining cells. There was also no expression of EGFR in cells comprising areas of basal cell hyperplasia and epidermoid metaplasia in the bronchus, or alveolar cell hyperplasia and columnar cell metaplasia in fibrotic lung tissue. Second, we examined the expression of EGFR in regenerating distal airway epithelial cells, which were experimentally produced by xenotransplantation of human lung tissue into the subcutaneous tissue of nude mice. There was also no expression of EGFR at any stage of regeneration from one week through six weeks after the transplantation. It is concluded that EGFR is not expressed, at least at an immunohistochemically detectable level, by airway epithelial cells of adult humans, not only in the quiescent state but also under conditions in which epithelial cells are stimulated to replicate. Thus, it appears unlikely that the EGF/EGFR system plays an important role in either maintenance or repair of airway epithelial cells in adult humans.

Epidermal growth factor receptor protein expression and gene amplification in the chemorefractory metastatic embryonal carcinoma

Testicular cancer is the most common cancer in young male patients. The combination of cisplatin-based chemotherapy and surgery has resulted in high cure rates. However, a small percentage of patients have cancers that are refractory to chemotherapy; treatment options for these patients are limited, and their prognosis is generally poor. Further studies are needed to explore the molecular pathogenesis pathways and potential targets of therapy for this group of highly aggressive tumors. We analyzed 21 patients who presented with metastatic embryonal carcinoma, were treated with chemotherapy, and subsequently underwent retroperitoneal lymph node dissection. Immunostaining for epidermal growth factor receptor (EGFR) was performed on paraffin-embedded tissue sections containing tumor from these specimens, using the avidin–biotin–peroxidase method. EGFR gene amplification was performed by interphase fluorescence in situ hybridization (FISH). Immunohistochemically, 9 of 21 cases (43%) demonstrated positive EGFR staining; 12 of 21 cases (57%) had absent or very limited EGFR expression. FISH revealed EGFR amplification in 1 case (5%), polysomy in 15 of 21 cases (71%), and normal disomy pattern in 5 of 21 cases (24%). A significant correlation between EGFR protein expression level and its chromosome polysomy/amplification was established (P=0.02). Our study showed that EGFR protein is frequently expressed in a subset of patients with chemorefractory metastatic embryonal carcinoma. EGFR chromosomal polysomy/amplification may be one of the mechanisms that cause increased EGFR protein expression, and could potentially be used as indication for anti-EGFR therapy.

New Horizons in Chemotherapy: Platforms for Combinations in First-Line Advanced Non-small Cell Lung Cancer

The treatment of advanced non-small cell lung cancer has evolved substantially during the last decade. Chemotherapy with a platinum-based doublet prolongs survival and improves quality of life in patients with good performance status. Recently, the addition of bevacizumab and the use of epidermal growth factor receptor inhibitors in appropriately selected patients have further improved the outcome of patients with advanced non-small cell lung cancer. Newer targeted agents are being developed and tested in the clinical arena at a rapid pace. In addition, the identification by clinical or molecular criteria of patient populations that benefit the most from these agents is under active investigation. In contrast, the development of newer cytotoxic agents, with innovative mechanisms of action, has been comparatively disappointing. Whether standard cytotoxic drugs are required as newer biologic agents are more frequently used or whether a more active and safer chemotherapy can be used as a template for combinations with biologic agents remains an important research topic.

MAPK overexpression is associated with anthracycline resistance and increased risk for recurrence in patients with triple-negative breast cancer

BackgroundTriple-negative breast cancer is estimated to account for 15%–20% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular factors in patients with triple-negative breast cancer. Patients and methodsTumor specimens from 109 patients with receptor-negative (estrogen receptor and progesterone receptor) breast cancer were analyzed for mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR) and phosphoinositol-3-kinase (PI3K) expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables, was investigated. ResultsFifteen (13.8%), 38 (34.9%) and 33 patients (30.3%) had positive staining for EGFR, MAPK and PI3K, respectively. MAPK was associated with anthracycline resistance (P=0.008) and lower MAPK score was significantly associated with shorter disease-free survival (P=0.029). Survival following relapse was significantly worse for those with a higher MAPK score (P=0.03). ConclusionMAPK is a significant prognostic and predictive factor in patients with triple-negative breast cancer. Furthermore, the level of staining among those with a positive MAPK expression may play a prognostic role at different stages of relapse. Further translational research is required to elucidate molecular mechanisms of tumor proliferation in this subset of patients.

Reactivity of integrin-linked kinase in human mesothelial cell proliferation

Integrin-linked kinase (ILK) is a protein kinase that links integrins and growth factors to a range of signalling pathways. ILK expression and activity are increased in a variety of human cancers. However, little is known regarding the role of ILK in malignant pleural mesothelioma (MPM). In this study, we assessed the expression of ILK in samples of human MPM, and compared it with the expression of epidermal growth factor receptor (EGFR). Thirty-four samples of human malignant mesothelioma were stained with a polyclonal antibody against ILK. Two independent observers evaluated the morphological pattern and intensity of staining. The findings have been compared with the patient's characteristics. Most MPM and mesothelial cell proliferation samples (87.9%) showed cytoplasmic ILK staining of varying intensity. Normal mesothelial cells and normal lung parenchyma did not stain for ILK at all. Conversely, the percentage of positive EGFR staining was somewhat lower (75.8%). The ILK-positive patients were significantly older than the ILK-negative patients. Here we report for the first time that ILK is indeed expressed in malignant mesothelioma. For further validation of a causal association between ILK and neoplastic mesothelial transformation, these immunohistochemical results should be supplemented with clinical and molecular biological data.

Expression of epidermal growth factor receptor in squamous cell carcinomas of the anal canal is independent of gene amplification

Immunohistochemical detection of expression of the epidermal growth factor receptor (EGFR) has been utilized to identify eligible patients with solid malignant tumors, including colorectal adenocarcinoma, for monoclonal antibody therapy (eg, cetuximab). The EGFR status in squamous cell carcinoma of the anal canal, an uncommon malignancy traditionally treated with chemoradiation, has not been well investigated. In this study, 38 primary squamous cell carcinomas of the anal canal were immunohistochemically examined for EGFR expression and analyzed by fluorescence in situ hybridization (FISH) for EGFR gene copy numbers. The results showed a variable degree of EGFR expression in 21 (55%) tumors, among which 13 (62%) cases exhibited a 2+ to 3+ staining pattern according to the Dako EGFR phamDx interpretation guide. There were no significant differences among tumors stratified by stage, degree of keratinization, or tissue block storage times. FISH analysis showed that none of the 34 cases with interpretable results had EGFR gene amplification. Increased gene copy numbers due to polysomy 7 were seen in seven of 18 (39%) cases that expressed EGFR protein and four of 16 (25%) cases that did not (P=0.3876). Ten (56%) tumors with positive EGFR staining showed a balanced disomy 7 pattern and one case with monosomy 7 exhibited strong EGFR expression (3+). These results demonstrate that EGFR is overexpressed in more than one-half of the squamous cell carcinomas of the anal canal through mechanisms other than gene amplification. These observations may have important therapeutic implications since EGFR-based targeted therapies have shown promise for other malignant neoplasms.

Prognostic significance of tumor angiogenesis, Ki 67, p53 oncoprotein, epidermal growth factor receptor and HER2 receptor protein expression in undifferentiated nasopharyngeal carcinoma--a prospective study.

This study prospectively examines the prognostic role of p53 oncoprotein (p53), Ki67-antigen (Ki67), tumor angiogenesis (MVD), epidermal growth factor receptor (EGFR), and HER2 receptor protein (HER2) expression in Chinese with undifferentiated nasopharyngeal carcinoma (NPC). Seventy-eight Chinese were recruited from October 1995 to July 1997 at the Prince of Wales Hospital, Hong Kong. Pretreatment immunohistochemical preparations of the primary tumor were made, and clinical data were collected prospectively until October 30, 2000. The markers were correlated with overall survival (OS), disease-free survival (DFS), time to progression (TTP), and UICC stage. On univariate analysis, EGFR expression correlated with poorer OS (p =.0001), DFS (p =.01), shorter TTP (p =.0001), and advanced T stage (p =.036). Strong EGFR expression, when compared with weak or moderate, was associated with poorer OS (p =.04) and shorter TTP in a subgroup of patients with UICC stage III-IV disease. HER2 expression was associated with advanced UICC stage (p =.006). The presence of p53 expression correlated with poorer DFS (p =.01) and a trend toward shorter TTP (p =.06). No correlation was found with Ki67-antigen or MVD. On multivariate analysis, only EGFR expression was significantly linked to shorter OS and TTP. EGFR expression in undifferentiated NPC is associated with a poor clinical outcome. A prognostic role of p53 and HER2 expression is suggestive but not consistently defined in this study. The relatively high prevalence of positive staining for EGFR supports the use of molecular targeted therapy in this disease.

Expression, action, and regulation of transforming growth factor alpha and epidermal growth factor receptor during embryonic and perinatal rat testis development.

The objective of the current study was to extend previous observations and examine the expression pattern and effects of transforming growth factor alpha (TGFalpha) and epidermal growth factor receptor (EGFR) on embryonic testis morphogenesis and growth. The expression of TGFalpha was determined after morphological sex determination (seminiferous cord formation at embryonic day 13 [ED13]) through perinatal testis development (postnatal day 5 [PD5]) with a quantitative reverse transcription-polymerase chain reaction procedure. Expression of messenger RNA (mRNA) for TGFalpha appeared to be more dynamic during testis development when compared with the expression of mRNA for EGFR. Message for TGFalpha was reduced at ED16 and PD4, and was elevated at PD0 during testis development. In contrast, EGFR mRNA levels were negligible at ED15 and were elevated constitutively from ED16 through PD5. Immunohistochemistry was conducted at ED14, ED16, ED19, PD0, PD3, and PD5 to localize cellular expression of both TGFalpha and EGFR. At ED16, positive staining for EGFR was localized to the cords, and by ED19, was mainly in the cords with slight expression in the interstitium. From PD0 to PD5, positive staining for EGFR was detected in the germ, Sertoli, and interstitial cells. Immunohistochemistry for TGFalpha detected localization at ED14 and ED16 to the Sertoli cells and to specific cells in the interstitium. From ED19 through PD5, TGFalpha was detected in the Sertoli, germ, and interstitial cells, and in endothelial cells within the interstitium. To determine the effects of TGFalpha on embryonic testis growth and seminiferous cord formation, ED13 testis organ cultures were treated with sense and antisense TGFalpha oligonucleotides. Antisense TGFalpha inhibited testis growth by 25%-30% in ED13 testis organ cultures when compared with sense oligonucleotide control pairs. To examine the effects of TGFalpha on perinatal testis growth, PD0 testis cultures were treated with different doses of TGFalpha. TGFalpha increased thymidine incorporation into DNA in PD0 testis cultures. Therefore, TGFalpha appears to have actions on both embryonic and perinatal testis growth. The regulation of TGFalpha and EGFR mRNA levels were examined using PD0 testis cultures treated with hormones that stimulate testis growth. Follicle-stimulating hormone (FSH) stimulated (P < .05) and testosterone tended to stimulate (P < .07) mRNA expression of EGFR. Epidermal growth factor stimulation of PD0 testis cultures did not affect levels of mRNA expression for EGFR, but did suppress expression of mRNA for TGFalpha. These results taken together demonstrate that TGFalpha can act to regulate early embryonic and perinatal testis growth. Furthermore, TGFalpha and EGFR expression can be regulated through growth stimulatory hormones such as FSH and testosterone.

Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression.

To determine whether cancer patients with tumor suppressor gene abnormality survive for a shorter time when their growth was stimulated by growth factors, we examined 290 non-small cell lung cancer (NSCLC) specimens for p53 and epidermal growth factor receptor (EGFR) protein expressions using immunohistochemical staining. The distribution of cases by pathological stage of tumor was 155 cases of stage I, 30 cases of stage II, 96 cases of stage III and 9 cases of stage IV. Pathological types were 142 adenocarcinomas, 127 squamous cell carcinomas, 17 large cell carcinomas and 4 other types of malignancy. Immunohistochemical staining was performed on the formalin fixed, paraffin-embedded materials with monoclonal antibodies DO-7 and clone EGFR.133. positive staining for EGFR was seen in 124 (42.8%) cases. More EGFR positive cases were found in squamous cell carcinomas than in non-squamous cell carcinomas (p=0.0121). Staining for p53 protein was observed in 147 (50.7%) specimens. Multivariate proportional hazard model analyses revealed EGFR protein expression as a risk factor in the patients with NSCLC (p=0.0240). Patients negative for both EGFR and p53 survived for a longer period of time (p=0.0427).

Co-overexpression of p53 protein and epidermal growth factor receptor in human papillary thyroid carcinomas correlated with lymph node metastasis, tumor size and clinicopathologic stage.

Expressions of p53 protein and epidermal growth factor receptor (EGFR) were immunohistochemically investigated in 111 patients with papillary thyroid carcinomas (PTC) in order to evaluate their co-expression in relation to lymph node metastases (LNM), tumor size and clinicopathologic stage. In PTC, positive staining for p53 in dewaxed sections was present in nuclei or cytoplasm, or in both, whereas surface linear or cytoplasmic staining for EGFR was observed with varying degrees of extent and intensity. Positive reaction (more than 10% of tumor cells positive) was observed in 65 cases (58. 5%) for p53, and in 87 cases (78.4%) for EGFR. A significant correlation was found between p53 protein and EGFR overexpressions (p<0.01). Notably, p53-positive cases always exhibited positive staining for EGFR. Forty-four patients (39.6%) exhibited concomitant LNM, most of whom had both p53 and EGFR expression in primary foci. Statistical analysis revealed that co-expression of p53 protein and EGFR was significantly correlated with LNM, tumor size and clinicopathologic stage, but no correlation was found between their co-expression and age or sex. Our findings suggest that overexpression of p53 protein or EGFR in PTC tends to be associated with a high frequency of LNM, increased tumor size and advanced clinicopathologic stage, and that co-expression of both p53 protein and EGFR may predispose to growth and progression of PTC. Our findings also suggest that p53 protein and EGFR expressions may be clinicopathologic and prognostic indicators of PTC.

Prognostic influence of the co-expression of epidermal growth factor receptor and c- erbB-2 protein in human lung adenocarcinoma

The epidermal growth factor receptor (EGFR) is structurally similar to the c- erbB-2 oncogene protein. One hundred and nineteen specimens of primary human lung adenocarcinoma were investigated immunohistochemically for the expression of EGFR and the c- erbB-2 protein. Positive staining for EGFR was evident in 55 (46%), and c- erbB-2 protein in 33 (28%) cases. Of the 119 cases, the number staining positively for both the EGFR and c- erbB-2 protein totalled 16 (13%). The incidence of both the expression of EGFR and the c- erbB-2 protein was greater in patients with metastasis1 (M1) than in those with MO ( P < 0.01). The 5-year survival rates of patients with EGFR positivity and those with EGFR negativity were 51% and 42% respectively, however, the results did not show statistical significance. On the other hand, the 5-year survival rates of patients with c- erbB-2 positivity and c- erbB-2 negativity were 30% and 52%, respectively, with statistical significance ( P < 0.05). Of the cases with EGFR positivity the 5-year survival rates of patients with c- erbB-2 positivity ( n = 16) and negativity ( n = 39) were 33% and 59%, respectively, with statistical significance ( P < 0.05). In contrast, for the EGFR negative cases, the 5-year survival rates of patients who were positive ( n = 17) and negative ( n = 47) for c- erbB-2 expression were 27% and 46%, respectively, which were not significantly different. Our data thus suggested that erbB oncogenes may play an important role in both the development of cancer and the prognosis of adenocarcinoma of the lung.

Immunohistochemical expression of epidermal growth factor receptor in benign and malignant lesions of the breast.

The expression of epidermal growth factor receptor (EGFR) was studied in benign and malignant tumors of the breast using a monoclonal antibody of this receptor. The benign lesions were obtained from mastopathy (14 cases), fibroadenoma (12 cases), and malignant lesions, and from papillo-tubular (17 cases), solid-tubular (15 cases), and scirrhous carcinomas (10 cases). The highest incidence of positive EGFR staining was found in the scirrhous carcinomas (70%). The incidence was moderate in tubular carcinomas (60-65%), and low in solid or papillary type (13-35%). Immunolocalization of EGFR staining was divided into 1) luminal-border positive type, 2) cell-membrane positive type, and 3) cytoplasm positive type. In benign lesions, EGFR expression was usually of the luminal border or cell membrane positive type. A heterogeneity of EGFR staining was found in malignant tumors, but evidence suggests in scirrhous carcinoma that EGFR expression is positively correlated with tumor cell proliferation.

Immunohistochemical expression of epidermal growth factor receptor in salivary gland tumours

Immunohistochemical localization of epidermal growth factor receptor (EGFR) in normal salivary glands and tumours (108 cases) was studied using a monoclonal antibody. In the normal salivary glands, EGFR was occasionally detected in ductal segments of intercalated, striated, and excretory ducts, but not in acinar cells. The frequency of positive EGFR staining in salivary gland tumours was not high: pleomorphic adenoma, 33.8%; mucoepidermoid tumour, 25.0%; adenolymphoma, 44.4%; and sialoadenocarcinoma, 66.6%. Pleomorphic adenomas showed positive staining for EGFR on the luminal side of luminal cells and in squamous metaplastic cells of tumour tissue. Some modified myoepithelial cells were also reactive whereas outer spindle tumour cells were unstained. Adenolymphomas regularly exhibited positive EGFR staining in the cell membrane; mucoepidermoid carcinoma displayed positive staining in cell membranes in epidermoid tumour cells and cytoplasmic staining in mucous-secreting tumour cells. Sialocarcinomas revealed cell membrane staining and whole cytoplasmic staining for EGFR. The immunohistochemical localization of EGFR could be classified into two types, one the cell membrane-positive type found in epithelial tumour cells, and the second the cytoplasmic positive type seen in normal ductal cells, the luminal tumour cells of pleomorphic adenomas and mucous-secreting tumour cells.