TGF-α Expression Research Articles

Tape stripping induces marked epidermal proliferation and altered TGF-α expression in non-lesional psoriatic skin

Psoriasis is a chronic inflammatory disorder characterized by epidermal hyperproliferation. Although recent evidence suggests that T cell activation is a primary trigger for psoriasis lesions, there may be alterations in the keratinocyte growth regulatory pathways which induce epidermal hyperproliferation in psoriatic patients. To test this hypothesis, we investigated the proliferative activity of epidermal keratinocytes 48 h after tape stripping, one of the standard mechanical ways to stimulate the epidermis, in 20 psoriasis patients and in 18 controls. Epidermal cell kinetics were assessed with DNA flow cytometry, the mitotic index, bromodeoxyuridine incorporation, Ki-67 antigen expression and DNA polymerase α expression. The expression of TGF-α and EGF receptors, critical mediators of keratinocyte proliferation, were also investigated immunohistochemically. The results of multiparameter assays showed that the baseline proliferative activity in uninvolved skin was the same in psoriasis patients and normal controls. After tape stripping, although both psoriasis patients and the normal controls showed significant increases in epidermal cell proliferation, the values of all the parameters investigated were significantly greater in the psoriasis patients than in the normal controls. EGF receptors were overexpressed in basal and suprabasal keratinocytes after tape stripping in both the psoriasis patients and the normal controls. In contrast, overexpression of TGF-α was only observed in the patients with psoriasis, which may explain their increased proliferative response to trauma.

Expression of Epidermal Growth Factor and Transforming Growth Factor Alpha during Ulcer Healing: Time Sequence Study

Background: Growth factors such as epidermal growth factor (EGF) and transforming growth factor alpha (TGFα) have been shown to share common receptor (EGFR) and to accelerate ulcer healing due to stimulation of cell proliferation, but the time sequence of expression of EGF and TGFα during ulcer healing has not been investigated. In this study the rate of cell proliferation and the gastric secretion and gene expression of mRNA for EGF and TGFα were determined during ulcer healing. Methods: Gastric ulcers were induced in 150 Wistar rats by serosal application of 100% acetic acid (ulcer area, 14 mm). Some of these animals were also equipped with a gastric fistula for the assessment of gastric secretion during ulcer healing. The animals were killed 0, 2, 4, 6, or 8 days after ulcer induction, and the ulcer area was determined. The mucosal sections with gastric ulcer were immunostained for proliferating cell nuclear antigen (PCNA) and for immunoexpression of EGF, TGFα, and EGFR. The expression of mRNA EGF and mRNA TGFα was also determined in the ulcer margin by reverse transcriptase (RT) polymerase chain reaction (PCR) using specific primers. Results: Two, 4, 6, and 8 days after ulcer induction the gastric ulcer area was gradually reduced from the initial size (day 0) by 47%, 70%. 80%, and 87%. respectively, and this was accompanied by an increase in PCNA with its maximum on day 4. The gastric acid and pepsin secretion was significantly reduced by 75% and 79%, respectively, on day 2 after ulcer induction but then the secretion tended to return to normal value by day 8. The expression of EGF, TGFα, and EGFR was negligible on day 0 but increased significantly during the healing, reaching maximum on day 4. Expression of EGF mRNA was detected on days 2, 4, and 6, and that of TGFα mRNA on days 2, 4. 6. and 8 after ulcer induction, with the most intense signals for both transcripts observed on day 2. Conclusions: 1) The enhancement in cell proliferation during ulcer healing may be mediated by increased release of EGF and TGFα; 2) the expression of EGF and TGFα mRNA precedes the overexpression of these growth factors at the ulcer margin during ulcer healing; and 3) the overexpression of growth factors coincides with the inhibition of gastric secretion and increased blood flow at the ulcer margin, indicating that these factors affect gastric secretion and blood flow in the course of ulcer healing.

<italic>De novo</italic> expression of transforming growth factor-α in parathyroid gland tissue of patients with primary or secondary uraemic hyperparathyroidism

The factors involved in abnormal parathyroid cell secretory function and growth in patients with primary and secondary hyperparathyroidism are still incompletely understood. We studied the expression of transforming growth factor-α (TGF-α), epidermal growth factor (EGF) and EGF receptor (EGF-R) at the gene message and the protein level in parathyroid tissue obtained from six patients with primary hyperparathyroidism, 15 patients with secondary uraemic hyperparathyroidism and five subjects with normal parathyroid tissue, using in situ hybridization and/or immunostaining technique. We found a consistent expression of TGF-α mRNA and protein in parathyroid endocrine cells of all six cases of primary parathyroid adenoma and in nearly all cases of secondary hyperplasia, in contrast to the absence of expression in normal parathyroid tissue. A marked expression of EGF-R mRNA and protein was also found in four of five tissue samples of primary parathyroid adenoma, in 13 of 15 tissue samples of secondary parathyroid hyperplasia and in most samples of normal parathyroid gland tissue. EGF mRNA and protein expression was undetectable in the majority of parathyroid tissue samples examined. Since TGF-α is known to bind to the EGF-R, the finding of an increased expression of TGF-α at the gene message and the protein level, together with a strong expression of EGF-R, in hyperplastic and adenomatous parathyroid glands suggests that this growth factor interacts with its receptor to promote parathyroid cell proliferation, perhaps by an autocrine mechanism.

Potentiation of diethylstilbestrol‐induced alterations in the female mouse reproductive tract by transforming growth factor‐α transgene expression

Neonatal estrogen exposure causes numerous abnormalities in the female reproductive tract, including carcinogenesis. One mechanism by which neonatal estrogen elicits teratogenic and carcinogenic effects is epigenetic and involves the modulation of a number of estrogen-regulated genes including epidermal growth factor (EGF). Because of the evidence that there is an integral relationship between the EGF family, estrogen action, and the regulation of the growth and differentiation of the reproductive tract, we used transforming growth factor-α (TGFα) transgenic mice to investigate the interaction of constitutive TGFα expression with the potent estrogen diethylstilbestrol (DES) in the induction of reproductive-tract alterations. Our study was designed to determine whether TGFα expression could modulate DES-induced carcinogenesis of the female mouse reproductive tract. The animals were homozygous TGFα transgenic female mice from the MT42 line and the parental CD-1 outbred mice. The presence of the TGFα transgene significantly increased the incidence of DES-induced vaginal adenosis, uterine endometrial hyperplasia, uterine polyps, hypospadia, benign ovarian cysts, and pituitary adenomas. However, constitutive TGFα expression did not promote reproductive-tract neoplasia. This study demonstrates that TGFα participates in the regulation of developmental and morphogenic events in the Müllerian duct and urogenital sinus, suggesting a role for TGFα in the pathogenesis of reproductive-tract diseases. Furthermore, we showed that although constitutive expression of the TGFα transgene did have an effect on the reproductive tract, TGFα overexpression alone could not substitute for DES as a reproductive-tract carcinogen or as a promoter of uterine neoplasia, indicating that DES-induced carcinogenesis requires events in addition to the overexpression of this single peptide growth factor. © 1996 Wiley-Liss, Inc. 1 This article is a US Government work and, as such, is in the public domain in the United States of America.

Expression ofneu and Neu differentiation factor in the olfactory mucosa of rat

The growth and differentiation of olfactory sensory neurons are regulated tightly. We had shown previously, by immunohistochemistry, that transforming growth factor-α (TGF-α) and epidermal growth factor (EGF) receptor are present in the olfactory epithelium of untreated adult rats and that TGF-α is a potent mitogen of olfactory epitheliumin vitro. Expression of EGF receptor and TGF-α was detected primarily in horizontal basal cells and supporting cells but rarely in globose basal cells, which suggested that EGF receptor is not a likely candidate for the mitotic regulator of sensory neurons. In order to expand the search for candidate regulators, we have now examined other members of the EGF family of receptors and ligands. By utilizing reverse transcriptase-polymerase chain reaction (RT-PCR) methodology, we have detected the messenger RNA encoding the protein of theneu gene (p185neu) and Neu differentiation factor (NDF) isoforms in the olfactory mucosa. Immunohistochemical localization of p185neu and NDF indicates expression of these proteins in the olfactory epithelium of adult rats in regions where globose basal cells and immature sensory neurons are found, as well as in the ensheathing cells of the olfactory nerve. The presence ofneu and NDF transcripts in the olfactory tissue and the localization of their encoded polypeptides to proliferative regions of the epithelium suggest involvement of these gene products in the regulated proliferation/differentiation of the sensory neurons.

Expression of IGF-1, TGF-α and p53 protein in imprint smears of bronchial biopsy specimens of lung cancer: Orphanidou D, Athanasiadou P, Toumbis M, Rasidakis A, Petrakakou E, Dimakou K et al. Department of Respiratory Medicine, Medical School University, Chest Diseases Hospital, 152 Mesogion Ave., Athens 115 27. Oncol Rep 1996; 3: 75–80

Expression of IGF-1, TGF-α and p53 protein in imprint smears of bronchial biopsy specimens of lung cancer: Orphanidou D, Athanasiadou P, Toumbis M, Rasidakis A, Petrakakou E, Dimakou K et al. Department of Respiratory Medicine, Medical School University, Chest Diseases Hospital, 152 Mesogion Ave., Athens 115 27. Oncol Rep 1996; 3: 75–80

Cell proliferation and expression of EGF, TGF-alpha, and EGF receptor in the developing primary palate.

Growth factors such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) play an important role in cell proliferation during embryogenesis. The purposes of the study were to characterize the expression patterns of EGF and TGF-alpha and their receptor, EGF receptor (EGF-R), and to analyze regional patterns of cell proliferation during primary palate morphogenesis when facial primordia outgrow and fuse to form the premaxillary and upper lip regions. The expression of all molecules was studied with indirect immunohistochemistry with conventional and/or confocal microscopes in normal days 10 and 11 CD1 mice. 5-Bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) were used as markers of cell proliferation. EGF, TGF-alpha, and EGF-R were found to have similar distribution patterns at all stages examined. In the anterior region of the face, the molecules were intensely localized at the tips and peripheral regions of the medial and lateral nasal prominences. Upon fusion of the facial prominences, all three molecules were present mainly at the fusion area and the tips and peripheral areas of the maxillary and nasal prominences. BrdU and PCNA were found to have distribution patterns similar to those of EGF, TGF-alpha, and EGF-R, with intense staining at the tips and peripheral regions of the facial prominences. These results show that EGF, TGF-alpha, and their receptor were expressed more intensely in regions of the developing primary palate where cell proliferation was most pronounced, and suggest that EGF, TGF-alpha, and EGF-R may play a role in cell proliferation during morphogenesis of the primary palate.

Detection of transforming growth factor-α protein and messenger RNA in hepatobiliary diseases by immunohistochemical and in situ hybridization techniques

Transforming growth factor-α (TGF-α) is a cytokines related to cell proliferation and transformation. Immunoreactive TGF-α protein is expressed in regenerating hepatocytes and interlobular bile ducts as well as in hepatocellular carcinoma. Although TGF-α is thought to play an important role in the intrahepatic biliary tree, its role in cellular physiology is poorly understood. This study investigates the expression of TGF-α and its messenger RNA (mRNA) in various hepatobiliary diseases. The authors showed by immunohistochemistry that TGF-α and its receptor, epidermal growth factor receptor (EGFR), were expressed in interlobular bile ducts, proliferating bile ductules, and most hepatocytes in various hepatobiliary liver tissues. They also showed by Western blot analysis that TGF-α protein was present in hepatic bile samples obtained from patients with obstructive jaundice. In situ hybridization showed that TGF-α mRNA was localized in hepatocytes of some pathological liver tissues, but it was absent in biliary epithelial cells of the same tissues. These findings suggest that TGF-α protein is produced by hepatocytes, and hepatocyte stimulation occurred as autocrine growth regulation. The release of TGF-α into hepatic bile caused biliary proliferation and transformation through EGFR, present on the existing cell surface membrane of biliary epithelial cells.

Expression of epidermal growth factor family proteins and epidermal growth factor receptor in human endometrium

The biological significance of epidermal growth factor (EGF)—related proteins in the development and progression of endometrioid endometrial carcinoma was studied. Expression of EGF-related proteins including EGF, transforming growth factor-α (TGF-α), cripto (CR), amphiregulin (AR), and EGF receptor (EGFR) were immunohistochemically examined. Results were then correlated with clinicopathologic findings and steroid receptor status in 12 specimens with normal endometrium, 13 with endometrial hyperplasia, and 40 with endometrioid endometrial carcinoma. EGFR, EGF, TGF-α, and CR iinmunoreactivities were observed in 58.3%, 66.7%, 91.6%, and 66.7% of normal endometrial specimens; 100%, 15.4%, 100%, and 30.8% of endometrial hyperplasia specimens; and 67.5%, 32.5%, 65.0%, and 65.0% of endometrial carcinoma specimens, respectively. AR immunoreactivity was not observed in any of the normal, hyperplastic, or neoplastic endometrium. The presence or absence of EGFR or TGF-α in endometrial carcinoma correlated with surgical stage, depth of myometrial invasion, and findings from peritoneal washing cytology. EGF expression significantly correlated with the age of the patients and that of CR with surgical stage and peritoneal washing cytological findings. There was a significant correlation between EGFR and TGF-α expression, and between EGF and TGF-α. Coexpression of EGFR and TGF-α, EGFR and CR, and TGF-α and CR in carcinoma specimens significantly correlated with advanced surgical stage, deeper myometrial invasion, and positive peritoneal washing cytology. In normal as well as hyperplastic endometrium, endometrial glands immunohistochemically positive for TGF-α were generally positive for ER, but in poorly differentiated endometrial carcinoma, cells positive for TGF-α tended to be negative for ER. The results of the present study show that among EGF-related proteins, expression of TGF-α and CR seem to be associated with the progression of human endometrioid endometrial carcinoma. Additionally, expression of TGF-α became increasingly estrogen independent with increasing histological carcinoma grades.

Proliferation of intrahepatic bile-duct epithelium in biliary atresia

Proliferating cell nuclear antigen (PCNA) and transforming growth factor α (TGFα) are considered as markers of cell proliferation. The expression of PCNA and TGFα was evaluated immunohistochemically using anti-PCNA antibody and TGFα in 31 patients with biliary atresia (BA) (15 jaundice-free and 16 with persistent jaundice) and 6 control infants. The labeling indices (LI) for PCNA- and TGFα-positive bile-duct epithelium in BA were 14.1±14.0% and 51.4±33.7%, respectively, which was significantly higher than in the controls (P <0.01). In BA, the number of PCNA-immunoreactive cells was higher in the peripheral bile ductules than in the central bile ducts of the portal tract (P <0.01). LI was not related to patient age at the time of hepatic portoenterostomy in two groups divided at the age of 60 days. Patients in the persistent jaundice group had greater expression of PCNA and TGFα (21.7±16.0% and 76.9±20.7%, respectively) compared to those in the jaundice-free group (6.0±2.7% and 24.3±20.9%, P <0.001). PCNA and TGFα expression in the bile-duct epithelium of the portal tract was closely related to prognosis in BA patients, and thus could be useful as a prognostic marker.

Short-term effects of pure anti-oestrogen ICI 182780 treatment on oestrogen receptor, epidermal growth factor receptor and transforming growth factor-alpha protein expression in human breast cancer

Expression of oestrogen receptor (ER), epidermal growth factor receptor (EGFR) and transforming growth factor-α (TGFα) proteins was assessed by immunocytochemistry on primary breast cancer specimens obtained before and following short-term (7-day) presurgical exposure to pure anti-oestrogen (7α- [9- (4,4,5,5,5-pentafluoropentylsulphinyl) nonyl] estra-1,3,5, (10)-triene-3,17 β-diol, ICI 182780) treatment and compared with no-treatment controls. Paired needle-core and mastectomy samples were obtained from 21 patients. Effects of ICI 182780 (10 −7M) on MCF7 breast cancer cell ER, EGFR and TGFα expression were also examined over 14 days. ER protein was significantly suppressed by ICI 182780 in vivo (P = 0.009) and comparative analysis of short term ICI 182780 effects in vitro, using ER-positive MCF7 cells, gave largely equivalent results. EGFR and TGFα protein levels were unaltered by treatment. ICI 182780 suppresses ER without a concomitant rise in either EGFR or TGFα.

Regulation of Mastomys ECL Cell Function by Transforming Growth Factor Alpha

Little progress has been made in the understanding of the pathobiology of gastric neoplasia over the past 4 decades. This reflects the paucity of information available regarding the biology of gastric mucosal cell proliferation. More recently it has become apparent that growth factor regulation of cell proliferation is of considerable relevance in initiating mucosal mitogenesis. We have recently identified the histamine secreting enterochromaffin-like (ECL) cell as a pivotal cellular regulator of gastric acid secretion. In addition to its critical role in initiating acid secretion, we have proposed that the ECL cell may produce agents responsible for the regulation of mucosal cell proliferation. We have therefore hypothesized that such a function may be subserved by production of transforming growth factor alpha (TGFα). TGFα is known to play a significant role both in normal physiology and in the transformation of naive cells into a neoplastic form. We therefore proposed that increased levels of gastrin induced by low acid states might stimulate TGFα secretion and that this agent might be capable of regulating ECL cell DNA synthesis and cell proliferation. We used the mastomys rodent to generate anin vivohy- pergastrinemia model using long-term histamine-2 receptor blockade (loxtidine 1 mg/kg/day). In order to evaluate the cell-specific effects, we developed a pure isolated ECL cell system from the mastomys stomach. This utilized pronase digestion (1.0 mg/ml) and EDTA exposure (1 mM) of the mucosa followed by particle size separation with countercurrent elutriation and density purification on a Nycodenz step gradient. ECL cells were obtained with a purity of 90–95%. Histamine secretion from ECL cells was measured by radioimmunoassay (RIA). TGFα content was measured by RIA, and TGFα expression was measured by RNAse probe protection assay. DNA synthesis was quantified by measuring bromo-deoxyuridine (BrdU) incorporation into cultured cells. TGFα levels were increased in fundic mucosa after 16 weeks of hypergastrinemia (from 4.3 ± 0.6 to 32.6 ± 2.6 fmole/mg protein,P< 0.05). TGFα message was identified in the ECL cells by RNAse probe protection assay, and was fourfold amplified in ECL cell tumors after 16 weeks of exposure to hypergastrinemia. Gastrin stimulated (10 nM) histamine secretion in isolated naive ECL cells was inhibited by TGFα (IC502 × 10−10M). DNA synthesis was stimulated by gastrin (EC502 × 10−11M) and TGFα (EC505 × 10−9M). These data are consistent with the proposal that elevated gastrin levels are associated with ECL cell TGFα production and that TGFα stimulates ECL cell DNA synthesis.

Adenocarcinoma of duodenum and ampulla of Vater: clinicopathology study and expression of p53, c-neu, TGF-alpha, CEA, and EMA.

Oncogenes, tumor suppressor genes, and growth factors are being explored as to their role in the initiation and progression of most neoplasms, but little information exists on the expression of oncoproteins or growth factors in adenocarcinoma of the duodenum or ampulla of Vater. This report covers expressions of p53, c-neu, TGF-alpha, CEA, and EMA in duodenal adenocarcinoma and ampullary adenocarcinoma, as well as correlations between expressions and tumor stage, histological grade and patient survival. The expression of p53, c-neu, TGF-alpha, CEA, and EMA has been studied in 15 duodenal adenocarcinomas and in eight ampullary adenocarcinomas by avidin-biotin-peroxidase complex indirect immunoperoxidase technique. The positive reaction for p53, c-neu, TGF-alpha, CEA, and EMA in duodenal adenocarcinoma was 20%, 60%, 60%, 73%, and 100%, respectively, and in ampullary adenocarcinoma, 13%, 100%, 50%, 63%, and 100%. Among the duodenal tumors, C-neu and p53 expression was noted more frequently in groups with high histological grades. Patients with c-neu positive duodenal adenocarcinoma had a shorter survival than the patients with c-neu negative duodenal adenocarcinoma (P < 0.01). C-neu product may serve as an unfavorable prognostic indicator in duodenal adenocarcinoma. No statistically significant correlation was found between the expressions of CEA, EMA, p53, and TGF-alpha and patient survival, tumor stage, or histological grade in either duodenal or ampullary adenocarcinomas.

白板症の免疫組織化学的検討

The correlation of epithelial dysplasia with the expression of TGF-α was evaluated in oral leukoplakia. For that purpose, the expression of TGF-α and proliferating cell nuclear antigen (PCNA) was examined immunohistochemically in thirty cases of tongue leukoplakia with epithelial dysplasia (mild dysplasia: 11 cases, moderate dysplasia: 10 cases, and severe dysplasia: 9 cases). In addition, the expression of these molecules in normal tongue epithelium and leukoplakia without epithelial dysplasia was also investigated.The results revealed that TGF-α was scarcely stained in normal epithelium. Whereas, in leukoplakia it was expressed in cells above the basal cell layer. PCNA was distributed chiefly in the basal cell layer in normal epithelium, while it was more widely distributed in leukoplakia. Both PCNA and TGF-α positivities have an increasing tendency in accordance with the grade of epithelial dysplasia.

Differential Expression of Transforming Growth Factor-α and Epidermal Growth Factor during Postnatal Development of Rat Submandibular Gland

The concentration and the localization of transforming growth factor (TGF)-α and epidermal growth factor (EGF) in the submandibular glands (SMGs) of male Wister rats of different ages (postnatal 0 to 10 weeks of age) were examined. Highest levels of TGF-α were seen early, at postnatal day 0; the levels dropped thereafter in an age-dependent manner, while EGF was not detectable before the third postnatal week. Immunoreactive localization of EGF was restricted to the granules of the granular convoluted tubule (GCT) cells in the mature SMGs, whereas TGF-α was observed throughout postnatal development over the entire duct system. TGF-α was demonstrated in the cytoplasm at early stages when the GCT granules were not observed and was also located on the granules at the late stage, as was the case for EGF, indicating that TGF-α is colocated with EGF in the mature SMG. These results demonstrate the differences between the expression of TGF-α and that of EGF in the developing rat SMG.

The expressions and changes of TGF—α,β Genes in human colorectal cancerous, paracancerous and normal mucosal tissues

Transforming growth factor α,β(TGF α,β) acted as positive and negative growth regulators respectively play an important role in the development and progression of colorectal carcinoma. In this study, the dot, Northern and Southern blot analysis were used to explore the expressions and changes of TGF-α,β genes of colorectal cancerous, paracancerous and normal mucosal tissues in 12 cases. The order of the expressions of TGF-a mRNA from high to low is cancerous, paracancerous and normal tissues in turn. In one case, the expression of TGF-α mRNA was much higher in paracancerous tissues, even than that in the cancerous tissues. The order of expressions of TGF-β mRNA from high to low was contrary to that of the TGF-α mRNA. That is from normal, paracancerous and cancerous tissues in turn. In two cases of patients, the expression of TGF-β mRNA were higher in paracancerous tissues than that in normal tissues. We also found that the amplification of TGF-α gene may be lead to the high expression of TGF-β mRNA were not known. These results indicate that the higher expression of TGF-α and the lower expression of TGF-β in cancerous tissues and the higher expressions of TGF-α, β in paracancerous tissues of some cases may be correlated with the development and progression of the colorectal carcinoma by autocrine or paracrine growth regulation.

Immunolocalization of transforming growth factor-α in normal and diseased human gastric mucosa

Roles for transforming growth factor—α (TGFα) in the stomach include cell migration and proliferation, inhibition of acid secretion, and cytoprotection. The authors have previously shown increased TGFα expression in rat gastric mucosa in response to acute gastric injury. They also have shown that TGFα immunoreactivity is increased in the gastric mucosa of four patients with Ménétrier's disease. To further characterize TGFα immunoreactivity in human gastric mucosa, the authors have performed immunohistochemical analysis with an anti-TGFα monoclonal antibody on human gastric biopsies ( n = 25) showing either normal ( n = 8), mild reactive/ reparative change in common conditions with or without associated gastritis ( n = 13), and exaggerated mucosal change in proliferative conditions (Ménétrier's disease, hypertrophic lymphocytic gastritis, and hyperplastic polyps) ( n = 17). All normal biopsies showed a predictable pattern of TGFα immunostaining, with significant positivity found only in foveolar cells at the luminal surface and parietal cells, sparing foveolar cells in the gastric pits, mucous neck cells and chief cells of the gastric glands. Three patients with mild foveolar hyperplasia without associated inflammation did not deviate from the normal pattern except in foci of reactive epithelial change. Ten of 11 patients with chronic active gastritis, in addition to this normal staining pattern, demonstrated significant immunoreactivity in deeper foveolar cells and mucous neck cells showing reactive epithelial changes, defined as the presence of nuclear enlargement and nucleolar prominence with or without mucin depletion. Three cases of ulceration with associated reactive epithelial changes also showed increased immunoreactivity. Furthermore, five cases of Ménétrier's disease with massive foveolar hyperplasia and minimal inflammation (MFH) and six cases with hypertrophic lymphocytic gastritis (HLG) have been studied, and both show full-thickness TGFα immunoreactivity restricted to the gastric epithelium. This pattern of staining is indistinguishable from that observed in two cases of hyperplastic polyps but differs significantly from that observed in cases of mild foveolar hyperplasia. These results further define patterns of TGFα immunostaining in normal, reactive/reparative and exaggerated proliferative human gastric biopsies, confirm participation of TGFα in the response to gastric mucosal injury, and provide additional support for a possible role for TGFα in the pathogenesis of proliferative gastric disorders including Ménétrier's disease, hypertrophic lymphocytic gastritis, and hyperplastic gastric polyps.

251 Expression of insulin like growth factor-I receptor and transforming growth factor-alpha in malignant effusion smears

The aim of this study was to investigate the expression of Insulin like Growth Factor-I receptor (IGF-Ir) and Transforming Growth Factor-alpha (TGF-α) in 42 effusion smears, using an immunocytochemical technique. We have studied 18 peritoneal and 24 pleural effusion smears from patients with endometrial (5), ovarian (7), colorectal (3), liver (3), breast (14) and lung (10) carcinomas. Fifteen effusion smears from patient with benign diseases were used as control group. IGF-Ir immunoreactivity was detected in 15/24 (62.5%; of pentoneal and 14/24 (58.3%) of pleural effusion smears. TGF-α immunoreactivity was observed in 12/18 (66.7%) of peritoneal and 10/18 of pleural effusion smears. Benign effusion smears were found to be negative for IGF-Ir and TGF-α immunoreactivity. These results suggest that the expression of IGF-Ir and TGF-α In malignant effusion smears plays an important role for the prediction of biologically high malignant potential

Expression of transforming growth factor alpha in the liver before and after interferon alfa therapy for chronic hepatitis B

The effect of interferon alfa (IFN-α) therapy on the expression of transforming growth factor alpha (TGF-α) in the liver during chronic hepatitis B was investigated. Serial liver biopsy specimens were evaluated from 35 patients who had participated in a randomized, controlled trial of recombinant human IFN-α for the treatment of chronic hepatitis B. Percutaneous liver biopsy specimens obtained before and 1 year after entry in the trial were sectioned and stained with a monoclonal antibody to TGF-α in an avidin-biotin-peroxidase-complex system. The expression of TGF-α in each section was evaluated blindly (with respect to treatment group and order of biopsies) and was numerically scored. There was no significant difference in TGF-α expression before or after therapy between 13 patients receiving daily IFN-α, 13 receiving alternate-day IFN-α, and 9 receiving no therapy. Sustained clearance of HBV-DNA and DNA polymerase activity occurred in 8 of 26 treated patients (“responders”); the 18 other patients were “nonresponders”. Expression of TGF-α before IFN-α therapy was significantly higher in responders than in nonresponders; after IFN-α therapy, TGF-α expression decreased significantly among responders compared with nonresponders and untreated controls. Thus, the level of expression of TGF-α in the liver, which was correlated with the severity of inflammation in the liver in this study, appeared to be predictive of the response to IFN-α therapy in chronic hepatitis B, with a higher level of expression indicating a greater likelihood that the patient would respond.

Expression of transforming growth factor alpha in the liver before and after interferon alfa therapy for chronic hepatitis B

The effect of interferon alfa (IFN-α) therapy on the expression of transforming growth factor alpha (TGF-α) in the liver during chronic hepatitis B was investigated. Serial liver biopsy specimens were evaluated from 35 patients who had participated in a randomized, controlled trial of recombinant human IFN-α for the treatment of chronic hepatitis B. Percutaneous liver biopsy specimens obtained before and 1 year after entry in the trial were sectioned and stained with a monoclonal antibody to TGF-α in an avidin-biotin-peroxidase-complex system. The expression of TGF-α in each section was evaluated blindly (with respect to treatment group and order of biopsies) and was numerically scored. There was no significant difference in TGF-α expression before or after therapy between 13 patients receiving daily IFN-α, 13 receiving alternate-day IFN-α, and 9 receiving no therapy. Sustained clearance of HBV-DNA and DNA polymerase activity occurred in 8 of 26 treated patients (“responders”); the 18 other patients were “nonresponders.” Expression of TGF-α before IFN-α therapy was significantly higher in responders than in nonresponders; after IFN-α therapy, TGF-α expression decreased significantly among responders compared with nonresponders and untreated controls. Thus, the level of expression of TGF-α in the liver, which was correlated with the severity of inflammation in the liver in this study, appeared to be predictive of the response to IFN-α therapy in chronic hepatitis B, with a higher level of expression indicating a greater likelihood that the patient would respond. (Hepatology 1995; 22:1021-1026.).