Epidermal growth factor receptor expression is associated with rapid tumor cell proliferation in renal cell carcinoma

Epidermal growth factor receptor (EGF-r) expression and tumor cell proliferation rate have been proposed as potential prognostic parameters in renal cell carcinoma (RCC). In this study, immunohistochemical stains using antibodies to EGF-r and the cell proliferation marker Ki-67 (MIB-1) were used to study the relationship between EGF-r expression, tumor cell proliferation, and prognosis in 50 non-papillary RCC extending beyond the renal capsule (pT3). A high Ki-67 labeling index (LI) was associated with poor patient prognosis (P < .05). Thirty-eight cases (76%) expressed strong cell membrane immunoreactivity for EGF-r. There was a tendency toward a shortened survival for EGF-r-positive tumors (P = .08). Tumor growth fraction (Ki-67 LI) was significantly higher in EGF-r-positive tumors than in EGF-r-negative tumors (P < .05), suggesting that rapid tumor proliferation might be responsible for the poor prognosis associated with EGF-r-positive RCC.     

Fibroblast growth factor receptor expression reflects cellular differentiation in human oral squamous carcinoma cell lines

This study examined the expression of fibroblast growth factor receptor 2 (FGFR 2) splice variants, IIIb and IIIc, in normal and malignant human oral keratinocytes and in normal oral fibroblasts by RT-PCR using both exon-specific primers and primers common to both FGFR 2 isoforms. Fibroblasts expressed exclusively FGFR 2/IIIc whilst the normal and malignant keratinocytes co-expressed FGFR 2/IIIb and FGFR 2/IIIc. Well-differentiated keratinocytes expressed proportionally more FGFR 2/IIIb than IIIc whereas the poorly-differentiated cells expressed more FGFR 2/IIIc than IIIb. The normal and malignant keratinocytes, but not fibroblasts, expressed an additional amplification product, which consisted of both IIIb and IIIc of FGFR 2 joined by an extra base pair and with the intronic sequence removed. The results indicate that the expression of FGFR 2 isoforms reflects the degree of cellular differentiation in normal and malignant human oral keratinocytes and that receptor complexes of FGFR 2/IIIb and IIIc may regulate ligand-receptor interactions.     

Epidermal growth factor receptor and transforming growth factor alpha expression in papillary and nonpapillary renal cell carcinoma: correlation with metastatic behavior and prognosis

Papillary renal carcinomas are a cytogenetically unique subset of renal carcinomas that have been reported to be clinically less aggressive. We have examined 19 papillary tumors for immunohistochemical expression of the epidermal growth factor receptor (EGF-R) and its ligand, transforming growth factor alpha (TGF-alpha). EGF-R and TGF-alpha expression was also studied in 149 nonpapillary tumors and 7 mixed papillary/solid tumors. EGF-R and TGF-alpha expression were compared to histology, stage, metastatic behavior, and survival. Formalin-fixed, paraffin-embedded nephrectomy specimens collected between 1977 and 1986 were stained with antibodies to EGF-R and TGF-alpha. Patients with papillary tumors were found to present with earlier stage disease and had significantly longer survival. Papillary tumors had a significantly lower rate of EGF-R positivity than solid pattern tumors (21% versus 73%, P < 0.001). Intermediate or strong cell membrane immunoreactivity for EGF-R was associated with high tumor grade and poor disease-specific survival. EGF-R positivity in the primary tumor was associated with the presence of metastatic disease and with metastatic spread to lung versus bone. Tumor parenchymal TGF-alpha staining was present in 50% of the cases and was not associated with stage or grade. Unrelated to tumor parenchymal TGF staining, tumor vessels stained for TGF-alpha in 56% of the cases. Vessel TGF-alpha staining was absent in papillary tumors (P < 0.001). The improved clinical behavior of papillary tumors as compared to nonpapillary renal tumors may be related, in part, to their relatively lower levels of EGF-R expression.     

Magnetic resonance imaging of esophageal squamous cell carcinoma using magnetite particles coated with anti-epidermal growth factor receptor antibody

This is a retrospective review of 29 posttraumatic pediatric and adolescent patients with surgically documented triangular fibrocartilage complex tears. All patients complained of ulnar wrist pain. Fifteen patients (52%) sustained distal radius fracture at the time of the original injury. Twenty-three (79%) of the triangular fibrocartilage complex tears were Palmer 1B lesions. There were 31A, 11C, and 21D lesions. All 1B, 1C, and 1D tears were repaired. Coexisting pathology was present in 25 patients (86%). This pathology included ulnar styloid nonunion, distal radioulnar joint instability, ulnocarpal impaction, distal radius deformity, and intercarpal ligament tears, which were treated by ulnar styloid nonunion excision, distal radioulnar joint stabilization, ulnar shortening, radius corrective osteotomy, and intercarpal ligament debridement, respectively. The length of the follow-up period averaged 21 months. Three patients were lost to follow-up. Outcomes were graded by a modification of the Mayo wrist score. Twenty-four patients (89%) had excellent results, 3 had good results.     

Epidermal growth factor receptor expression in oligodendroglial tumors

The pretreatment characteristics of 210 patients with multiple myeloma, observed between 1980 and 1994, were evaluated as potential prognostic factors for survival. Multivariate analysis according to Cox's proportional hazard model identified in the 160 dead patients with myeloma, among 26 different single prognostic variables, the following factors in order of importance: beta 2-microglobulin; bone marrow plasma cell percentage, hemoglobinemia, degree of lytic bone lesions, serum creatinine, and serum albumin. By analysis of these variables a prognostic index (PI), that considers the regression coefficients derived by Cox's model of all significant factors, was obtained. Using this it was possible to separate the whole patient group into three stages: stage I (PI < 1.485, 67 patients), stage II (PI: 1.485-2.090, 76 patients), and stage III (PI > 2.090, 67 patients), with a median survivals of 68, 36 and 13 months (P < 0.0001), respectively. Also the responses to therapy (P < 0.0001) and the survival curves (P < 0.00001) presented significant differences among the three subgroups. Knowledge of these factors could be of value in predicting prognosis and in planning therapy in patients with multiple myeloma.     

Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter

BACKGROUND: Squamous cell carcinomas of the head and neck (SCCHN), unlike normal mucosal squamous epithelial cells, overexpress epidermal growth factor receptor (EGFR) messenger RNA and protein. EGFR protein is required to sustain the proliferation of SCCHN cells in vitro. To determine whether EGFR expression contributes to tumor growth, we investigated the effect of suppressing EGFR expression in tumor xenografts through in situ expression of antisense oligonucleotides. METHODS: Intratumoral cationic liposome-mediated gene transfer was used to deliver plasmids capable of expressing sense or antisense EGFR sequences into human head and neck tumors, which were grown as subcutaneous xenografts in nude mice. The oligonucleotides were expressed under the control of the U6 RNA promoter. RESULTS: Direct inoculation of the EGFR antisense (but not the corresponding sense) plasmid construct into established SCCHN xenografts resulted in inhibition of tumor growth, suppression of EGFR protein expression, and an increased rate of apoptosis (programmed cell death). Sustained antitumor effects were observed for up to 2 weeks after the treatments were discontinued. CONCLUSION: These results suggest that interference with EGFR expression, using an antisense-based gene therapy approach, may be an effective means of treating EGFR-overexpressing tumors, including SCCHN.     

Vascular endothelial growth factor expression in head and neck squamous cell carcinoma

BACKGROUND: Angiogenesis is an essential process required for growth and metastasis in cancer. In breast, gastric, and prostate cancer, vascular endothelial growth factor (VEGF) has been implicated in angiogenesis; however, little is known about VEGF in HNSCC. In this study, we hypothesize that VEGF is present in elevated levels in HNSCC and may therefore play a role in promoting angiogenesis. METHODS: We obtained tumor tissue from 63 HNSCC patients undergoing primary resection. All tissue samples were analyzed by immunohistochemistry (IHC) techniques for the presence and localization of VEGF; however, only 36 had sufficient amounts of tissue for quantitative analysis of VEGF by ELISA. Nine control specimens taken from patients undergoing uvulopalatopharyngoplasty were also analyzed. RESULTS: In all 63 of our patient samples we found VEGF to be present and localized to the cancer cells and endothelial cells. The poorly differentiated cancer cells stained more intensely in comparison with the well-differentiated ones. There was a 20-fold increase in the patient levels when compared with controls levels (P > or =0.05). Analysis by enzyme-linked immunosorbent assay revealed elevated mean levels of VEGF (241 +/- 326 pg/mg total protein [TP]) with a range of 2 to 1484 pg/mg TP. The control specimens had mean levels of 13 +/- 11 pg/mg TP and a range of 1 to 78 pg/mg TP. Patients who exhibited higher levels of VEGF tended to have a higher rate of disease recurrence (P < or =0.048) and shorter disease-free interval (P < or =0.05). CONCLUSIONS: The expression of VEGF in elevated levels in the HNSCC tumor microenvironment appears to be associated with more aggressive disease. Based on our results, VEGF may be an important angiogenic factor associated with cancer cells and endothelial cells in HNSCC. Further studies are needed to better define the role of VEGF in HNSCC and its role as a potential target for therapeutic intervention.     

Epidermal growth factor family and renal cell carcinoma: expression and prognostic impact

OBJECTIVE: Expression and prognostic impact of some exponents of the epidermal growth factor (EGF) family in renal cell carcinoma (RCC) were examined. MATERIALS AND METHODS: EGF, transforming growth factor-alpha (TGF-alpha), EGF receptor (EGF-R), and c-erb B-2 were determined immunohistochemically in formalin-fixed paraffin-embedded tumor samples of 30 patients with locally confined RCCs. The prognostic significance of these growth factors and their receptors as well as of tumor stage and malignancy grade was examined with respect to survival and tumor recurrence by following up the fate of the patients after nephrectomy (mean follow-up time 5.2 years). RESULTS: The members of the EGF family and their receptors studied were expressed to a variable degree in all RCCs investigated. However, using log-rank tests in Kaplan-Meier plots only tumor stage (p < 0.0007) and malignancy grade (p < 0.007) but none of the growth factors or receptors studied (p > 0.05, respectively) exhibited prognostic significance with respect to both survival and disease-free period. On the contrary, there was a significant correlation between EGF and TGF-alpha (p < 0.001), EGF and EGF-R (p = 0.028), EGF-R and c-erb B-2 (p = 0.0009), and-inversely related-between TGF-alpha and tumor stage (p = 0.047) and between EGF-R and malignancy grade (p = 0.03). The coexpression of the factors studied also showed no prognostic relevance. CONCLUSION: The expression of these members of the EGF family seems not to bear evaluable prognostic information for clinical use in the case of RCC.     

Absence of epidermal growth factor receptor expression in squamous cell carcinoma of the uterine cervix is an indicator of limited tumor disease

The expression of growth factors is considered as an important diagnostic and prognostic feature in tumor pathology. We investigated the value of the immunohistochemical EGF-receptor expression (EGF-R) in 30 squamous cell carcinomas of the uterine cervix, treated by radical hysterectomy and lymphadenectomy according to the Wertheim-Meigs-Okabayashi technique. Immunohistochemical reactions were performed on 4 microm sections from paraffin-embedded tissue, using an indirect peroxidase method. The staining results were evaluated semiquantitatively as negative (n=9; 30%) or as slightly, moderately or severely positive (n=21; 70%). The EGF-R-negative tumors were found in less advanced tumor stages. None had invaded into the parametrium (100%), eight were staged as T1 (89%), seven as N0 (78%), and seven showed no evidence for lymphangiosis carcinomatosa (78%). The respective values for the EGF-R-positive tumors ranged from 52% to 67%. However, only the difference in parametral invasion (EGF-R-negative: 0%, EGF-R-positive: 38%) was statistically significant (p=0.0306), probably due to the small number of cases. The EGF-R-expression was not correlated to histomorphological tumor grading. The results of this study indicate an inverse correlation between EGF-R expression and tumor spread. Assuming that this trend could be confirmed by a larger group of patients, immunostaining for EGF-R in a tumor biopsy could be useful to adapt surgical strategies and adjuvant therapy in the individual patient. Moreover, the EGF-R is an interesting target for immunotherapeutic approaches in squamous cell cervical carcinoma.     

Overexpression of scatter factor and its receptor (c-met) in oral squamous cell carcinoma

HYPOTHESIS: Scatter factor (SF) is a pleiotropic growth factor that recently has been shown to induce epithelial cell proliferation, random motility, and invasion via interaction with its receptor, a tyrosine kinase encoded by the c-met proto-oncogene. Studies involving a variety of solid tumors have suggested that overexpression of the SF/c-met ligand-receptor pair is associated with the acquisition of a malignant phenotype. We hypothesize that SF and c-met are overexpressed in epithelial malignancies of the head and neck including squamous cell carcinoma (SCC) of the oral cavity. STUDY DESIGN: Immunohistochemical staining of randomly selected normal, dysplastic, and malignant oral tissues. METHODS: Formalin-fixed, paraffin-embedded tissues were obtained from the Department of Oral Pathology at Shands Hospital (University of Florida), Gainesville, Florida. Examples of mild dysplasia, severe dysplasia, well-differentiated SCC, moderately differentiated SCC, and poorly differentiated SCC were randomly selected from the dictated reports of one of two staff oral pathologists. Histologically normal margins of each specimen served as normal controls. The tissues were immunohistochemically stained using commercially available antibodies against SF and c-met. Appropriate negative controls were run with each batch to ensure staining specificity. Evaluation of staining intensity was carried out using a computerized image analysis system. A one-way analysis of variance (ANOVA) with pairwise multiple-comparison procedures (Fisher method) was used to analyze the data. RESULTS: Statistically significant differences (P < .0001) in the intensity of staining were noted between the malignant and normal and the malignant and dysplastic tissues for both SF and c-met. No differences were appreciated when staining of normal and dysplastic sections of the SF-stained tissue were compared. CONCLUSIONS: The results suggest that the SF/c-met ligand-receptor pair is overexpressed in SCC of the oral cavity.     

Epidermal growth factor (EGF) and EGF receptor in hypospadias

Environmental oncology is a discipline concerned with studies of multi-aspect relationships between environment and living organisms exposed to the modifying influence of carcinogenic agents. It also deals with general biological regularities involved in neoplasm development as well as their prevention in different species including man, animals and plants. Various investigations conducted at the Laboratory and supported with Russian and foreign grants (1991-1996) are briefly discussed. Among them are biotesting environmental carcinogens (aminoanthraquinons, by-products of drinking water chlorination, development of new testing systems and objects of detection involved in identification of genotoxic substances (criteria for formation of short-term test batteries and evaluation of perspectives, methods and results), investigation of xenobiotic metabolic activation (enzyme imprinting in adult animals), search for anticarcinogens (classification of carcinogenesis inhibitors, development of testing systems for modifiers selection), and establishing environment-related regularities of tumor growth. Vistas in environmental oncology development are discussed.     

Epidermal growth factor induces terminal differentiation in human epidermoid carcinoma cells

In this study, spermatogenesis in the adult Djungarian hamster is described. Undifferentiated spermatogonia topographically arranged as Asingle (A(s)), Apaired (Apr), and Aaligned (Aal) spermatogonia were observed, as were six generations of differentiating spermatogonia (A1, A2, A3, intermediate, B1, and B2). The differentiating spermatogonia divided at regular intervals during the cycle of the seminiferous epithelium. Mitosis of these cells was observed at the transition from stage IX to stage X (mitosis of A1 into A2 spermatogonia), at the transition from stage XII to stage I, at the transition from stage II to stage III, at the transition from stage IV to stage V, at the end of stage VI, and at approximately the middle of stage VII. Cellular associations in the cycle of the seminiferous epithelium are described. The seminiferous epithelium was divided into 12 stages, based upon the developmental steps in spermiogenesis, and the frequency of these stages was determined. The duration of the cycle of the seminiferous epithelium, determined by [3H]thymidine incorporation, was shown to be 7.90 +/- 0.01 (mean +/- SEM) days.     

Epidermal growth factor receptors and their ligands in non-small-cell lung carcinoma

The study was carried out in 178 women without grave obstetrical or extragenital diseases. In group 1 labor pain was relieved by prolonged epidural anesthesia with 2% lidocaine solution (2-2.5 mg/kg), in group 2 prolonged epidural anesthesia with 1% lidocaine solution (1 mg/kg) and 0.01% clofelin (1 microgram/kg) was administered. Central hemodynamics, heart rhythm, external respiration function, uterine contractility, and fetal intrauterine status were assessed. The findings indicate that none of the methods had a negative impact on the vital parameters of women and newborns at any stage of anesthesia. However, a combination of epidural clofelin (1 microgram/kg) with lidocaine permits an appreciable decrease in the doses of both drugs without decreasing the efficacy of anesthesia. This method has a favorable effect on the course of labor: the mouth of the womb opens sooner at a lower uterine activity and there are no negative effects on the fetus and newborn.     

Circulating platelet-derived endothelial cell growth factor increases in hepatocellular carcinoma patients

BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that is expressed in various cancer tissues. Little is known regarding plasma PD-ECGF levels in patients with chronic liver disease such as chronic hepatitis (CH), cirrhosis, and hepatocellular carcinoma (HCC) with cirrhosis. The expression of PD-ECGF in HCC tissues also remains to be clarified. METHODS: Plasma PD-ECGF levels in patients with chronic liver disease were determined with an enzyme-linked immunoadsorbent assay system using the mouse monoclonal antibodies specific to PD-ECGF. These were cross-sectionally compared among groups of normal persons, CH, cirrhosis, and HCC patients. The HCC patients were classified into two groups based on TNM stage: early and advanced stage disease groups. PD-ECGF expressions in HCC tissues were immunohistologically examined. RESULTS: The plasma PD-ECGF levels from the normal individuals and those with CH, cirrhosis, and HCC specimens were 4.2+/-0.5, 4.3+/-0.6, 4.6+/-1.1, and 6.0 +/-2.5 U/mL, respectively. The plasma PD-ECGF concentration was highest in HCC (P < 0.05). No significant difference was found among the normal subjects, CH, and cirrhosis specimens. Plasma PD-ECGF concentrations were significantly higher in the advanced stage disease HCC group compared with the early stage disease group (6.75+/-2.62 U/mL vs. 4.19+/-0.34 U/mL) (P < 0.05). Immunohistochemical expression of PD-ECGF in HCC cells increased significantly compared with normal liver cells (P < 0.05). CONCLUSIONS: Circulating PD-ECGF plasma level might be a new tumor marker for progression in patients with HCC. Immunohistological findings correspond to elevation of the plasma PD-ECGF in HCC patients. It is possible that increased production of PD-ECGF in HCC cells causes abundant neovascularization.     

Epidermal growth factor receptor immunoreactivity in gallbladder and extrahepatic biliary tract tumours

BACKGROUND: Brain dysfunction is common in patients with advanced liver disease; it is often manifested as hepatic encephalopathy, but its cause is not clearly understood. METHODOLOGY: Intracranial blood flow velocity parameters, including peak systolic velocity, end diastolic velocity and mean velocity of both middle cerebral arteries were measured by transcranial Doppler ultrasonography in 37 patients with cirrhosis without encephalopathy (16 Child's A, 10 Child's B and 11 Child's C) and 12 normal controls. The cause was alcohol-related in 24 and non-alcohol-related in 13. RESULTS: No significant differences in any of the Doppler parameters were detected in Child's group A when compared with controls. However, a statistically significant decrease in middle cerebral artery blood flow velocity was evident when Child's B and C patients without clinically apparent encephalopathy were compared with controls irrespective of the cause. Our results demonstrate that intracranial blood flow is abnormal in patients with advanced liver disease without clinically apparent encephalopathy.     

Expression of the opioid growth factor, [Met5]-enkephalin, and the zeta opioid receptor in head and neck squamous cell carcinoma

Heterogeneity of DNA content in multiple hepatocellular carcinomas (HCCs) was investigated by flow cytometry in 62 tumours from 26 patients who had undergone surgical treatment for multiple synchronous HCCs. Heterogeneity of DNA content was defined (a) when tumours had a different DNA ploidy pattern or (b) when the difference in the DNA index of the aneuploid clone was more than 0.1. A tumour with DNA aneuploidy was observed in 17 (66%) of the 26 patients. Heterogeneity of the DNA content was demonstrated in 12 (46%) out of 26 patients: in ten cases by definition (a) and in two cases by definition (b). Histological examination revealed that, of the 12 patients with a heterogeneous tumour DNA content, seven (58%) had a heterogeneous and the remaining five (42%) had a homogeneous type and grade of differentiation among the tumours, showing the absence of a relationship between histological heterogeneity and DNA content. The present results suggest the clinical relevance of DNA content analysis for identifying the clonal origin of multiple HCCs.     

Epidermal growth factor receptor and its inhibition in radiotherapy: in vivo findings

Increasing evidence shows that dysregulated epidermal growth factor receptor (EGFR) signalling plays an important part in neoplasia. When over expressed or mutated, EGFR is frequently associated with more aggressive tumour growth, poor patient prognosis and resistance of tumours to cytotoxic agents, including radiation. The present studies with murine carcinomas showed that there is an inverse correlation between the level of EGFR and tumour radiocurability. Likewise, the present clinical study in patients with head and neck cancer shows that EGFR over expression correlates with poorer tumour response to radiotherapy. Adding EGFR to tumour cells in vitro protected cells against the cytotoxic action of radiation, whereas blocking EGFR with anti-EGFR antibodies enhanced cell radiosensitivity. A casual relationship between EGFR and increased cellular resistance to radiation was established by transferring the EGFR gene into low EGFR-expressing radiosensitive tumour cells, which then become radioresistant. Radiation activated EGFR and its downstream signalling pathways in radioresistant but not in radiosensitive tumours, and this effect was associated with increased resistance to radiation, and enhanced repopulation in irradiated tumours. Increasing evidence shows that blockage of EGFR or interference with any of the steps in its signal transduction cascade can counteract negative outcomes of EGFR signalling, which has recently been explored as a therapeutic strategy in cancer treatment. The present findings demonstrate that treatment of human tumour xenografts with C225, an anti-EGFR monoclonal antibody, dramatically enhanced tumour response to radiation. Overall, the findings show that over expression of EGFR may serve as a predictor of tumour treatment outcome by radiotherapy and as a therapeutic target to enhance the efficacy of radiotherapy.     

Transforming growth factor beta 1 induces squamous carcinoma cell variants with increased metastatic abilities and a disorganized cytoskeleton

Previous studies indicated that mouse transformed keratinocytes undergo an epithelial-fibroblastic conversion when cultured in the presence of TGF-beta1. This conversion is associated in vivo with a squamous-spindle carcinoma transition. We derived epithelioid (A6, FPA6) and spindle (B5) clonal cell variants from a squamous carcinoma cell line (PDV) after treatment with TGF-beta1. FPA6 cells were isolated from the ascites fluid of an A6-tumor-bearing mouse. FPA6 and A6 cell lines produced in nude mice mixed carcinomas with a squamous and poorly differentiated component. Both cell lines coexpressed keratins and vimentin and synthesized E-cadherin protein, although FPA6 cells cultured at early passages (FPA6-ep) had reduced levels of E-cadherin mRNA and increased synthesis of keratin K8, a marker of malignant progression. Immunofluorescence analysis revealed that FPA6-ep cells exhibited a disorganized cytoskeleton with keratins forming focal juxtanuclear aggregates and loss of F-actin stress fibers and cortical bundles, and E-cadherin was localized in the cytoplasm out of cell-cell contact areas. Sporadic cells in A6 and PDV cultures also presented those anomalous keratin structures, suggesting that FPA6 cells originated from a subpopulation of A6 tumor cells that metastasized into the peritoneal cavity. The analysis of the spontaneous and experimental metastatic potentials of the cell lines showed that epithelioid and fibroblastic cell variants had acquired metastatic abilities compared to PDV which was nonmetastatic. The FPA6-ep cell line exhibited a highly aggressive behavior, killing the animals at about 17 days after intravenous injection of the cells into athymic mice. The phenotype of FPA6-ep cells was unstable and reverted at later passages in which the normal organization of keratin and F-actin in filaments and the localization of E-cadherin at cell-cell contacts were restored. This phenotypic reversion occurred concomitantly with a reduction of the experimental metastatic potential of FPA6 cells.     

Epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor in labial salivary glands in Sj?gren's syndrome

OBJECTIVE: Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) affect cells through binding to a shared EGF receptor (EGF-R), which is a transmembrane protein with tyrosine kinase activity. They exert trophic effects on vascular endothelial, salivary acinar, and ductal and mucosal epithelial cells. In Sj?gren's syndrome (SS) focal sialadenitis leads to salivary gland tissue damage, diminished salivary flow, and changes in the oral epithelium, a complex referred to as xerostomia. We compared the localization of EGF, TGF-alpha, and EGF-R in labial salivary glands in SS and in healthy controls. METHODS: Labial salivary gland tissues of 12 patients with SS and 7 healthy controls were stained with the immunohistochemical peroxidase-antiperoxidase method for EGF, TGF-alpha, and EGF-R. RESULTS: Immunoreactivity for both EGF and TGF-alpha was found in endothelial cells of blood vessels and in some ductal epithelial cells. TGF-alpha, but not EGF, was also found in some acinar cells. EGF-R was found in endothelial, acinar, and salivary duct epithelial cells. There was no difference in the expression of EGF-R between diseased and healthy specimens, but both EGF and TGF-alpha were diminished in SS. CONCLUSION: The interrelated localization of EGF-R and its ligands, EGF and TGF-alpha, suggests an autocrine, juxtacrine, and paracrine mitogenic/trophic role for them and thus a role in the maintenance of the secretory and excretory cells of the normal salivary glands. The trophic effects on acinar cells seem not to be mediated by EGF, but more likely by TGF-alpha. The diminished expression of EGF and TGF-alpha indicates a failure of this trophic system in SS, which may contribute to the acinar atrophy and secondary changes thereof, including atrophy of the oral mucosa.