Influence of Transforming Growth Factor-alpha on Expression of Matrix metalloproteinase-2 and Matrix metalloproteinase-9 mRNA in Mouse Embryos / 대한산부인과학회잡지

OBJECTIVE: To investigate the influence of transforming growth factor-alpha (TGF-alpha) on the expression of Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) mRNA in mouse embryos. MATERIALS AND METHOD: Eight-cell stage mouse embryos were cultured for 48hours with TGF-alpha at concentrations of 1, 10 and 100 ng/ml. Embryos not treated with TGF-alpha served as control. Reverse transcription-polymerase chain reaction (RT-PCR) has been used to examine the expression of MMP-2 and MMP-9 mRNA in developed blastocysts. Following reverse transcription, strategically designed nested primers, optimized for specificity, were used for amplification from the cDNA equivalent of a single embryo. The products were then verified by restriction enzyme digestion and sequence analysis. Results were analyzed with analysis of variance (ANOVA) and statistical significance was defined as p<0.05. RESULTS: The relative quantities (relative volume x intensity) of MMP-2 mRNA expressed in embryos of 10 and 100 ng/m of TGF-alpha treatment groups were significantly increased than in the control and 1 ng/ml of TGF-alpha treatment group (67.2+/-7.5 and 77.4+/-11.6 vs. 38.6+/-4.5 and 43.4+/-6.1, p<0.001). The relative quantities of MMP-9 mRNA of 100 ng/ml TGF-alpha treatment group was significantly increased than in the control and 1 ng/ml TGF-alpha treatment groups (67.6+/-6.5 vs. 36.6+/-14.2 and 40.2+/-11.3, p<0.001, p<0.01, respectively). CONCLUSION: This study suggests that TGF-alpha itself may induce the expression of MMP-2 and 9 mRNA in mouse embryos.

Expression of TGF-alpha, beta1, beta2 in Pterygial Mast cell

PURPOSE: To evaluate whether TGF-alpha, beta1, beta2 are expressed in pterygial mast cell and the difference between each growth factor exists. METHODS: We prepared 10 pieces each of excised normal conjunctiva, primary pterygium, recurrent pterygium from human eyes and then fixed those in 4% paraformaldehyde solution. The tissues were embedded in paraffin and slide samples taken from those. After that, we observed mast cells stained by immunohistochemistry against each of TGF-alpha,beta1 ,beta2 and compared the staining features between them, and we also confirmed metachromatic staining of the mast cell with toluidine blue. RESULTS: As compared with normal conjunctiva, in primary and recurrent pterygia, those counts of mast cells expressing TGF-alpha, beta1, beta2 were increased respectively with statistical significance and especially, those counts for TGF-beta1 in primary pterygium were 9 times as high as in normal conjunctiva. CONCLUSIONS: Pterygial mast cells are considered to play an important role in fibrovascular proliferation of pterygium by synthesizing and secretion of TGF-alpha, beta1, beta2 . Especially, TGF-beta1 is thought to play a more important role than TGF-alphaandbeta2 in primary pterygium.

The Effect of Transforming Growth Factor-alpha on the Preimplantation Development, Implantation and Epidermal Growth Factor Receptor Expression in Mouse Embryos / 대한산부인과학회잡지

OBJECTIVE: To investigate the influence of transforming growth factor-alpha (TGF-alpha) on preimplantation development, implantation and epidermal growth factor receptor (EGFR) expression in mouse embryos. MATERIALS AND METHODS: Eight-cell stage mouse embryos were cultured for 48 hours with TGF-alpha at concentrations of 1.0, 10 and 100 ng/ml. Embryos not treated with TGF-alpha served as control. The percentages of embryos which developed to blastocyst stage, expanded, hatched blastocyst stage and in vitro implantation at 48 hours were determined. Riverse transcription-polymerase chain reaction (RT-PCR) has been used to examine the expression of EGFR in developed hatched blastocysts. Following reverse transcription, strategically designed nested primers, optimized for specificity, were used for amplification from the cDNA equivalent of a single embryo. The products were then verified by restriction enzyme digestion and sequence analysis. RESULTS: The percentages of embryos which developed to blastocyst stage were significantly higher following incubation with TGF-alpha at concentration of 10 ng/ml(p<0.05). The percentages of embryos which developed to expanded blastocyst stage were significantly higher in TGF-alpha treatment group at concentration of 100 ng/ml(p<0.05). The percentages of embryos which developed to hatched blastocyst stage were significantly higher following incubation with TGF-alpha at concentration of 10 ng/ml and 100 ng/ml(p<0.05). The percentages of implanted blastocyst in vitro were significantly higher following incubation with TGF-alpha at concentrations of 100 ng/ml compared to the control(p<0.05). The mRNA concentration of EGFR in embryos treated with 100 ng/ml of EGF was significantly higher than those of the control and other EGF treatment groups(p<0.005, p<0.05, p <0.05, respectively). CONCLUSION: TGF-alpha may stimulatory role in embryonic development, implantation and expression of EGFR in embryo itself. These results suggest that TGF-alpha may act directly on the mouse embryo and favor its implantaion, irrespective of the presence or absence of the endometrium.

Effect of Transforming Growth Factor-beta1 on Expressions of Epidermal Growth Factor and Transforming Growth Factor-alpha in DU145 Androgen-Independent Prostate Cancer Cells / 대한비뇨기과학회지

PURPOSE: This study was designed to identify the possible mechanism of insensitivity of DU145 prostate cancer cells to the transforming growth factor (TGF)-beta1-mediated growth inhibition. MATERIALS AND METHODS: DU145 cells were treated with 4, 40, 100 pM TGF-beta1 for 3, 6, 9 days. Initially we performed the growth assay. After that, we analysed the change of cell cycle using fluorescence flow cytometry. At each time point, Western blot analysis with cell pellets was performed to investigate the change of expressions of epidermal growth factor(EGF), TGF-alpha, EGF receptor(EGFR) and TGF receptorII(TbetaR-II) proteins. RESULTS: The growth rate of TGF-beta1-treated cells was initially suppressed, but over time returned to control level. Flow cytometric analysis revealed that TGF-beta1-treated cells showed an increase in apoptotic/G1 phases, and concurrent decrease in S, G2/M phases until 6days. On day 9, however, TGF-beta1-treated cells showed a persistent increase of apoptotic unclei in spite of recovery of apoptotic/G1, S and G2/M phases. Western blot analysis showed that the intensity of EGF or TGF-alpha band decreased in dose-sependent manner on day 6. However, the intensity of each band increased up to the control level on day 9. the expression of EGFR or TbetaR-II protein did not change after treatment of TGF-beta1. CONCLUSIONS: these results suggest that EGF and TGF-alpha sould mediate in part the escape fron the inhibitory effect of TGF-beta1 in DU145 cells.

An Immunohistochemical study on the Expression of EGFR, TGF-alpha and Ki-67 in the Uterine Cervical Neoplasia / 대한산부인과학회잡지

OBJECTIVE: Cervical carcinoma of the uterus, the most common maliganacy among women in Korea, which its etiology and pathogenesis are not yet determined. Recently, since it has been found about the function of the growth factor and its receptor, involved in the regulation of cellular growth and differentiation, many studies have been undertaken about the role of growth factors and its receptors in the growth and differentiation of the tumor cell. METHODS: In this study, we examined the expression of EGFR, TGF-alpha and Ki-67 in 50 CINs and 20 invasive cervical cancers using immunohistochemical stain. RESULTS: Positive rate of EGFR was 92% in CIN, 80% in invasive cancer, negative rate of TGF-alpha was 74% in CIN, 80% in invasive cancer and Ki-67 labelling index(LI) in normal basal cell, CIN I-II, CIN III were 5+/-0.7, 13+/-2.5, 65+/-5.4 repectively and in invasive cancer, LI was over 90. from this result as cervical carcinoma progresses, the expression of EGFR and Ki-67 increase while that of TGF-alpha decreases. CONCLUSION: As cervical carcinoma progress, the expression of EGFR and Ki-67 increase while that of TGF-alpha decreases. Further studies on the expression of EGFR and TGF-alpha and its growth-stimulation mechanism in cervical carcinoma are warranted to establish the pathogenesis of the cervical carcinoma.

The Effects of Transforming Growth Factor beta1 on Apoptosis in Rat Hepatocellular Carcinoma

Based upon the concept that carcinogenesis is associated with apoptosis, specific therapies designed to enhance the susceptibility of cancer cells to undergo apoptosis could be developed. Thus, in this paper, it was designed to investigate whether, using rat animal model with chemical-induced hepatocellular carcinoma, TGF-1 in vivo could induce apoptosis in cancer. The chemical hepatocarcinogenic procedure of Solt-Farber method was used on Sprague-Dawley rats. Experimental groups were divided into group A treated with the standard Solt-Farber regimen of diethylnitrosamine (DEN) and 2-Acetaminofluorene (AAF), group B TGF-, group C TGF-1, and group D adriamycin after hepatocellular carcinoma developed. For detection of apoptotic cells, apoptotic indices were examined by the in situ end DNA labelling method. The expression of proliferating cell nuclear antigen was examined by immunohistochemical staining. Apoptosis of rat hepatocellular carcinoma cells increased significantly to 4.92+/-2.32/HPF in the group C compared with the control group (A) (2.54+/-1.13/HPF; P<0.05). Two distinctly different populations of proliferating hepatocellular carcinoma cells were identified. The cells at G1/S boundary (weak granular staining) increased to 15.75+/-6.19/HPF and 6.45+/-2.93/HPF in the groups C and D, respectively, but decreased to 2.42+/-2.06/HPF in the group B compared with the control group (A) (6.38+/-2.18/HPF; p<0.05). The cells at S phase (strong granular staining) increased to 3.37+/-2.69/HPF in the group B but decreased to 0.32+/-0.47/HPF in the group D (p<0.05). In conclusion, these results indicate that the TGF-1 may be used as an effective anticancer agent.

Expression of Epidermal Growth Factor Related Peptides, EGF-R, and c-erbB-2 and Their Relationship with the Prognostic Factors in Gastric Carcinoma

Recent investigations have revealed that autocrine growth factors and their receptors are closely related and play an important role in controlling cancer cell growth. We performed an immunohistochemical study on the expression of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGF-R), c-erbB-2, and PCNA labelling index in 60 cases of human gastric carcinomas. TGF-alpha was detected in 38 cases (63.3%), EGF in 26 cases (43.3%), EGF-R in 44 cases (73.3%), and c-erbB-2 in 18 cases (30%). These growth factors, EGF-R and c-erbB-2, were found more often in advanced gastric cancers. The PCNA labeling index was significantly higher in tumors with the expression of EGF-R or c-erbB-2. Tumors with simultaneous expression of EGF, TGF-alpha, EGF-R and c-erbB-2 was associated with a high PCNA labeling index. A correlation was observed between the synchronous expression of growth factors and its receptors and histological differentiation. The results suggest that the expression of EGF, TGF-alpha, EGF-R and c-erbB-2 are closely related and plays an important role in the growth and progression of human gastric carcinoma.

Clinical Significance of Expression of Epidermal Growth Factor, Epidermal Growth Factor Receptor, Transforming Growth Factor-alpha in Aural Cholesteatoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Aural cholesteatoma is characterized by hyperproliferation of keratinizing squamous epithelium in the middle ear cleft. Although the exact mechanism of bone destruction in aural cholesteatoma is still not clear, it was recently reported that a variety of cytokines, including epidermal growth factor (EGF), epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) were over-expressed in aural cholesteatoma. The aim of this study is to demonstrate that there is over-expression of EGF, EGFR, and TGF-alpha in cholesteatoma and to evaluate the relationships between their expressions and clinical severity of the disease. MATERIALS AND METHODS: Expressions of EGF, EGFR, TGF-alpha were evaluated by immunohistochemical staining of cholesteatoma tissue and normal external auditory canal skin. The degree of expression were measured either by subjective observation and semi-quantitative image analysis. Both subjective scores and density scores were compared with clinical variables, such as the presence of preoperative otorrhea, complication, ossicular destruction, and the stage of cholesteatoma. RESULTS: The expression of EGF and TGF-alpha were more increased, particularly in the suprabasal layer of cholesteatoma epithelium than the normal skin. When the ossicular destruction and more extended cholesteatomas were present, the expressions if EGF and TGF-alpha were increased in the cholesteatoma tissues. CONCLUSION: The degree of expression of EGF and TGF-alpha in cholesteatoma may represent the clinical severity of the disease.

Expression of p53, mdm-2, nm23 and TGFalpha in Primary and Second Primary Cancers in Multiple Head and Neck Cancers / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Development of second primary cancer is an important biological characteristic of head and neck squmaous cell carcinoma. In the past, the development of second primary cancer has been explained by the field cancerization theory. However, recent reports support the common common clonal origin theory. Common clonal origin theory states that following the initial transformation, the progeny of the transformed clone spread through the mucosa and gives rise to the geographically distinct but genetically related tumor. The objective of this study is to compare the expression pattern of p53, mdm-2, nm23 and TGFalpha which are proteins involved in the development, growth and metastasis of tumor in primary and second primary cancers of multiple head and neck cancer. MATERIALS AND METHODS: Expression of p53, mdm-2, nm23 and TGFalpha were analysed by immunohistochemical study of 12 paraffin embedded sections from 6 patients (3 synchronous tumors, 3 metachronous tumors) who were surgically treated for multiple head and neck cancer. RESULTS: p53, mdm-2, nm23 and TGFalpha were expressed in the same pattern in 3 patients (50%) of primary and second primary cancers. CONCLUSION: In our study, we observed the same expression patterns in 3 cases; however, it was difficult to conclude based on this result alone the clonality relationship between primary and second primary cancer. We suggest that further studies using molecular biological techniques are needed to identify the early genetic events of carcinogenesis.

A Study on the Expression of Transforming Growth Factor-alpha, Epidermal GrowthFactor and Epidermal Growth Factor Receptor in Thyroid Tumors / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Cell proliferation and differentiation are regulated by growth factors and growth factor receptors. Inappropriate expressions of growth factors and altered responsiveness of growth factor receptors may influence the biological and clinical phenotype of tumor. The purpose of this study is to investigate the relationship between the expressions of TGF-alpha, EGF, EGFR and clinical behaviors in thyroid tumors. MATERIALS AND METHODS: The material consisted of 19 papillary carcinomas, 8 follicular carcinomas, 6 anaplastic carcinomas, 8 follicular adenomas and 5 normal thyroid tissues. The authors performed immunohistochemical staining for TGF-alpha, EGF and EGFR. RESULTS: Positive staining for TGF-alpha was found in 84.2% of papillary carcinomas, 100% of follicular carcinomas, 83.3% of anaplastic carcinomas and 25% of follicular adenomas. EGF was positive in 57.8% of papillary carcinomas, 25% of follicular carcinomas, 0% of anaplastic carcinomas and 25% of follicular adenomas. EGFR was positive in 52.6% of papillary carcinomas, 85.7% of follicular carcinomas, 83.3% of anaplastic carcinomas and 75% of follicular adenomas. There was no statistical relationship between regional lymph node metastasis, primary tumor size, patient's age and positive expression rates for TGF-alpha, EGF and EGFR. CONCLUSION: TGF-alpha expression was statistically higher in the malignant thyroid tumors than in benign thyroid tumors. However, the expression of EGFR was shown to be higher in thyroid tumors than in the normal thyroid tissues, but there was no statistical difference between benign and malignant tumors. EGF expressions demonstrated no statistical significance in thyroid tumors.

Prognostic Significance of Histologic Features, DNA Content, Expression of Proliferating Cell Nuclear Antigen (PCNA), c-fos Protein and Transforming Growth Factor (TGF)-alpha and -beta in Giant Cell Tumor of Bone / 대한암학회지

PURPOSE: This study was attempted to investigate the prevalence of the expression of c-fos protein, TGF-alpha and -beta, PCNA , DNA ploidy pattern and histopathological parameters of giant cell tumor (GCT) of bone and to correlate with prognosis and to extend our understanding on tumorigenesis of GCT. MATERIALS AND METHODS: Twenty eight cases of paraffin-embedded tissue were studied, classified as recurrent (5 cases) and non-recurrent group (12cases) within the limits of the cases which afforded surgical material on first operation. RESULTS: No significant difference was observed in cellularity of stromal cells, atypia of stromal and giant cells, presence of hemorrhage and necrosis between recurrent and non-recurrent group. However, presence of more than 10 mitotic figures in 10 high power fields in recurrent group was significantly higher than non-recurrent group (p<0.05). The immunoreactivity for PCNA was seen only in nuclei of stromal cells, whereas nuclei of giant cells showed negative staining. The positivity of PCNA revealed no significant difference between non-recurrent (mean; 40.9%) and recurrent group (34.4%). The expression of c-fos oncogene was seen in 5 cases (100%) in recurrent group, and 8 cases (66.7%) in non-recurrent group, and no significant difference was seen. No significant difference of expression of TGF-alpha was seen in 5 cases (100%) in recurrent group and in 11 cases (91.7%) in non-recurrent group. The expression of TGF-beta in stromal cells was significantly higher in non-recurrent group (80%) compared to recurrent group (100%) (p<0.05). In DNA analysis out of 18 cases, 4 cases (22.2%) were aneuploidy and 14 cases (77.8%) were diploidy. Among 4 aneuploidy cases, 3 cases (75%) had no recurrence, and 1 case (25%) had metastasis to lung and expired. No significant difference of DNA ploidy pattern was seen between the recurrent and non-recurrent group. CONCLUSION: Presence of more than 10 mitotic figures in 10 high power fields and less expression of TGF-beta are related to higher possibility of recurrence and it is suggested that the number of mitotic figure (more than 10/10HPF) and expression of TGF-beta could be helpful parameters in predicting recurrence of GCT.

Stimulation of c-myc protooncogene expression by transforming growth factor a in human ovarian cancer cells

To investigate whether transforming growth factor alpha (TGF alpha) treatment of human ovarian cancer cells was associated with the induction of c-myc protooncogene, the expression of this gene in NIH:OVCAR-3 cells was examined. TGF alpha induced increase in c-myc mRNA level, with a peak after 1 h of treatment; this stimulation was dose-dependent, with an optimal concentration of 5 ng/ml TGF alpha. Its primary action is probably at the transcription level since the half-life of c-myc mRNA measured in the presence of actinomycin D was not modified by TGF alpha treatment. In addition, TGF alpha stimulation of c-myc mRNA did not require protein synthesis since it was not suppressed by cycloheximide treatment. Antisense phosphorothioate oligonucleotide to c-myc specifically inhibited the TGF alpha-stimulated c-Myc protein expression and growth of NIH:OVCAR-3 cells. Our results indicate that induction of c-myc expression by TGF alpha plays an important role in the growth of NIH:OVCAR-3 cells.

Expression of TGF-alpha, p53 and PCNA in Laryngeal Dysplasia / 대한이비인후과학회지

BACKGROUND: Transforming growth factor(TGF-alpha) is a polypeptide which is structurally related to epidermal growth factor(EGF) and binds to the epidermal growth factor receptor(EGFR). TGF-alpha utilizes EGFR to increase the activation of tyrosine kinase to involve in signal transduction of cellular growth. TGF-alpha synthesis occurs in a variety of neoplastic cells. p53 is a tumor-suppressor gene. There is a strong corrleation between immunohistochemical p53 positivity and p53 mutations in lung and laryngeal carcinoma. PCNA is expressed by cycling cells in late G1, S and G2 phase, and may be used to indicate the degree of cellular proliferation. OBJECTIVES: To evaluate whether TGF-alpha, p53 and PCNA can be used as an indicator to malignant transformation of dysplasia in larynx or not. MATERIALS AND METHODS: The authors investigated the TGF-alpha score, p53 immunoreactivity and PCNA proliferating index by immunohistochemical staining in 30 laryngeal dysplasia from 1992 to 1995. RESULTS: Dysplasia with malignant transformation showed values of 5.46 for TGF-alpha, 29.2 for PCNA proliferating index and 37.5 for p53 immunoreactivity. Dysplasia without malignant transformation showed values of 1.88 for TGF-alpha, 8.6 for PCNA proliferating index and 4.5 for p53 immunoreactivity. Conclusions: The results suggest that TGF-alpha, p53 and PCNA could be an useful indicator to predict the progression of laryngeal dysplasia.

Expressions of the Tumor Associated Proteins and Their Correlation with the Pathologic Features in Childhood Hepatoblastoma

Hepatoblastoma is a rare malignant liver tumor found in children. Its biological characteristics and prognostic factors have not been well known. We investigated 29 cases of hepatoblastoma, registered in university hospitals in Seoul from 1984 to 1996. By the immunohistochemical method, p53, Waf-1 (p21), bcl-2, heat shock protein 70 (hsp70), c-jun, transforming growth factor-alpha (TGF-alpha) expressions were studied. Those data were compared with clinico-pathologic features; age, sex, tumor size, tumor stage and histologic subtypes. Expression of p53 and bcl-2 were each observed separately in single cases. Expression of c-jun was more frequently noted in patients at higher stages. Expression of TGF-alpha decreased in the order of pure fetal, mixed, embryonal and small cell anaplastic subtypes. Cumulative survival rate was lower in females than in males and in patients with a higher tumor stage. According to histologic subtypes, survival rates decreased in the order of pure fetal, mixed, embryonal and small cell anaplastic subtypes. Survival rate was lower in patients with c-jun expression. Group of TGF-alpha labelling index under 19 showed a lower survival rate than that over 19. In conclusion, we found that tumor associated proteins, c-jun and TGF-alpha, are closely related to the prognosis of hepatoblastoma but p53 and bcl-2 may not be related to it.

A comparison Study of Expression of Transforming Growth factor - alpha in Keratoacanthomas and Squamous Cell Carcinomas / 대한피부과학회지

BACKGROUND: Transforming growth factor-(TGF-alpha) is a acidic, heat-stable, 50 amino acid polypeptide which is related to cellular proliferation, malignant transformation, and angiogenesis. There are many similarities between keratoacanthoma(KA) and squamous cell carcinoma(SCC). So, it is often difficult to differentiate keratoacanthoma and squamous cell carcinoma, clinically and histologically. OBJECTIVE: Our purpose was to examine the patterns of TGF-alpha expression on KA and SCC using immunohistochemical staining and to evaluate the usefulness of the immunohistochemical staining with antihuman TGF-alpha antibody on differentiation between KA and SCC. METHODS: Formalin-fixed, paraffin-embedded specimens that had confirmed to KA(n=12) or SCC(n=10) were performed by immunoperoxidase staining with monoclonal antihuman TGF-alpha antibody RESULTS: All of KA dmonstrated a diffuse pattern within tumor lobules, but, at the peripheral rim of cells, showed unstained pattern. In contrast to KA, 40% of the SCC had patchy infiltration within tumor lobules, and 60% of the SCC had diffuse pattern which was similar to the pattern found in KA. All of SCC showed well-defined staining at peripheral cells. CONCLUSION: Immunohistochemical staining with antihuman TGF-alpha antibody could be used on differentiation between KA and SCC.

A comparison Study of Expression of Transforming Growth factor - alpha in Keratoacanthomas and Squamous Cell Carcinomas / 대한피부과학회지

BACKGROUND: Transforming growth factor-(TGF-alpha) is a acidic, heat-stable, 50 amino acid polypeptide which is related to cellular proliferation, malignant transformation, and angiogenesis. There are many similarities between keratoacanthoma(KA) and squamous cell carcinoma(SCC). So, it is often difficult to differentiate keratoacanthoma and squamous cell carcinoma, clinically and histologically. OBJECTIVE: Our purpose was to examine the patterns of TGF-alpha expression on KA and SCC using immunohistochemical staining and to evaluate the usefulness of the immunohistochemical staining with antihuman TGF-alpha antibody on differentiation between KA and SCC. METHODS: Formalin-fixed, paraffin-embedded specimens that had confirmed to KA(n=12) or SCC(n=10) were performed by immunoperoxidase staining with monoclonal antihuman TGF-alpha antibody RESULTS: All of KA dmonstrated a diffuse pattern within tumor lobules, but, at the peripheral rim of cells, showed unstained pattern. In contrast to KA, 40% of the SCC had patchy infiltration within tumor lobules, and 60% of the SCC had diffuse pattern which was similar to the pattern found in KA. All of SCC showed well-defined staining at peripheral cells. CONCLUSION: Immunohistochemical staining with antihuman TGF-alpha antibody could be used on differentiation between KA and SCC.

Expression of p53, c-myc, Transforming Growth Factor-alpha and -beta in Human Epithelial Ovarian Tumors

The author examined expression of tumor-related antigens, such as p53 tumor supressor protein, c-myc, TGF-alpha, and TGF-beta proteins in 75 cases of surgically resected epithelial ovarian tumors. Peroxidase immunohistochemistry was used to determine the frequency of expression, the relationship among expression of these antigens and histopathological spectrums, and clinical stage, and their potential prognostic significance. The results are summarized as follows. A positive correlation was found between expression of p53(P=0.02), c-myc(P=0.03), and TGF-alpha(P=0.001) and histological degrees of malignancy(benign, borderline, or malignant) in epithelial ovarian tumors. A significant correlation was found between expression of p53 and histological degrees of malignancy in serous ovarian tumors(P=0.003) and mucinous tumors (P=0.049). A significant correlation was also found between expression of c-myc and the histological grade of serous carcinomas(P=0.02). A correlation between expression of these antigenic proteins and clinical stage of epithelial ovarian tumors was not demonstrated. Expression of p53 and c-myc was closely correlated with expression of TGF-alpha irrespective of the histological degrees of malignancy and type of epithelial ovarian tumors(0.4 < or = K < or = 0.7). The results of this study support the ideas that expression of c-myc and TGF-alpha might be a useful prognostic indicator in human ovarian carcinomas, and expression of p53 could be another indicator of prognosis, as the expression of p53 is characteristic in that the expression is mostly seen in invasive ovarian carcinomas.

Immunohistochemical Study of TGFalpha , EGF and EGF Receptor on the Epithelial Tumors of the Skin / 대한피부과학회지

BACKGROUND: Several reports have demonstrated that TGFalpha and EGF are mitogenic for keratinocytes. Whenther its expression on epithelial tumors is a marker of malignancy or signifies an important step in the development of neoplasia is poorly understood. EGF receptors are also present in normal epidermis and epithelial tumors but their physiological roles are not yet understood. OBJECTIVE: Our purpose was to examine the staining patterns of TGFalpha, EGF and EGF receptors on the npithelial tumors of the skin, and to investigate kinetics of expression of EGF receptors. METHODS: We performed immunoperoxidase staining(ABC technique) with monoclonal anti-TGFalpha antibody, polyclonal anti-EGF antibody and polyclonal anti-EGF receptor antibody on the formalinfixed, paraffin-embedded tissue specimens of benign, premalignant and malignant skin tumors. RESULTS: The density of the expression of TGFalpha and EGF was not correlated with the degree of the malignancy of the epithelial tumors and is neither constant in any kind of the tumors. However the infiltrative type of basal cell carcinoma(BCC) is stronger that its solid type on the expression of TGFalpha and EGF. All benign tumors demonstrated a diffuse pattern within tumor lobules. pression of TGFalpha and EGF. All benign tumors demonstrated a diffuse pattern within tumor lobules. Focal TGFalpha immunostaining was seen in three of 10 squamous cell carcinomas(SCC) and four of 10 BCCs. TGFalpha immunostaining was absent from the outermost one to two layers of tumor lobules of all keratoacanthomas. The specimens which increased the expression of TGFalpha and EGF tended to decrease the expression of EGF receptor. CONCLUSION: These data suggest that the density of immunohistochemical expression of TGFalpha and EGF may be not dependent on the differentiation of tumor cells, and the pattern of immunohistochemical expression of TGFalpha can differentiate SCC from benign tumors such as keratoacanthoma. FGF receptor may be occupied by both of TGFalpha and EGF. With the receptors being occupied, a down regulation of the receptors may occur which results in decreased EGF receptor expression.