Epidermal Growth Factor Receptor Content Research Articles

A bivalent single-chain antibody-toxin specific for ErbB-2 and the EGF receptor.

ErbB-2 and EGF receptors are often co-expressed in human tumors and have been shown to synergize in the transformation of cells in experimental model systems. Transactivation of ErbB-2 can occur via ligand-induced heterodimerization with EGF receptor or other members of the ErbB family of receptor tyrosine kinases. We have previously described the potent anti-tumoral activity of the monospecific single-chain antibody-toxins scFv(FRP5)-ETA and scFv(225)-ETA binding to, respectively, ErbB-2 and the EGF receptor. Here we report the construction and functional characterization of a novel bivalent, bispecific single-chain antibody-toxin, scFv2(FRP5/225)-ETA. The fusion protein consists of 2 scFv domains specific for ErbB-2 and the EGF receptor linked to a modified Pseudomonas exotoxin A. ScFv2(FRP5/225)-ETA displayed in vitro cell killing activity on tumor cells overexpressing either ErbB-2 or the EGF receptor similar to that of the monospecific toxins. It was more potent in vitro and in vivo in inhibiting the growth of tumor cells expressing both receptors. Treatment of A431 cells with scFv2(FRP5/225)-ETA led to an increase in EGF receptor and ErbB-2 phosphotyrosine content, most likely via the induction of receptor heterodimers. This may explain the enhanced toxicity of the bispecific antibody-toxin.

A novel action of epidermal growth factor in rat granulosa cells: its potentiation of gonadotrophin action.

It is well known that epidermal growth factor (EGF) induces down-regulation of LH receptors and desensitization to gonadotrophin stimulation in gonadal cells, including granulosa cells. In a previous study we showed that EGF receptor levels in rat granulosa cells were increased up to fourfold after 96 h of culture with human GH in the presence of FSH, and the present study has evaluated the action of EGF on these cells. The induced EGF receptors were identical in size to the pre-existing receptors as assessed by affinity labelling with 125I-EGF. After 48 h in culture, various amounts of EGF (0.5-10 ng) were added and the cells were cultured for a further 48 h. The addition of EGF caused down-regulation of LH receptors in cells expressing high levels of EGF receptors. However, this down-regulation was less than that in control cells. After the cells were washed, cAMP synthesis in response to human chorionic gonadotrophin (hCG) increased by two to three times the control value and this increase was closely correlated with an increase in EGF receptor content. However, stimulation with cholera toxin or forskolin showed no such augmentation, indicating that it may not be due to quantitative alterations in G proteins and their effector systems. Induction of EGF potentiation required long-term exposure to EGF, for at least more than 24 h. In addition, progesterone synthesis was sensitive to stimulation with lower doses of hCG. These findings indicate that the activation of hGH-induced EGF receptors may potentiate gonadotrophin action in granulosa cells.

Immunohistochemical detection of epidermal growth factor receptor (EGF-R) in paraffin sections of breast carcinoma tissue: correlation and clinical significance

Analyses of the level of expression of the epidermal growth factor receptor (EGF-R) of breast cancer tumours may add independent information about the prognosis for individual patients. Furthermore, the use of monoclonal antibodies directed against EGF-R as therapeutic tools (e.g., Mab 425) requires a reliable evaluation of the individual EGF-R content. Various analytical methods have been published, including (1) biochemical detectonn of EGF-R by a radiolabelled physiological ligand, (125I)EGF, (2) enzymatic analyses of EGF-R content (IEMA), (3) immunological analyses of EGF-R content with a monoclonal antibody (ELISA), and (4) immunohistochemical EGF-R detection. Studies with immunohistochemical analyses of EGF-R overexpression in formalin-fixed, paraffin-embedded tumour samples are rare. In a retrospective study, we examined the clinical data from 142 patients and the EGF-R expression in their formalin-fixed, paraffin-embedded tumour samples. The average follow-up was 69 months. EGF-R expression was compared to oestrogen (ER) and progesterone (PgR) receptor expression, histological grade, tumour size, lymph node metastases and menopause. 52 of 142 tumours were EGF-R positive. EGF-R overexpression correlated with high tumour grade, large tumours and elevated numbers of lymph node metastases. There was no significant correlation between ER or PgR and EGF-R expression. Determination of EGF-R overexpression revealed no significant difference in disease-free interval (DFI) or overall survival (OS). In this study, the determination of EGF-R in formalin-fixed, paraffin-embedded tumour samples proved feasible. Unfortunately, this did not add any additional information concerning DFI or OS.

Epidermal growth factor receptor content in rat prostatic adenocarcinoma: effects of endocrine treatment.

Epidermal growth factor receptor (EGF-R) was studied in Dunning prostatic cancer models using competitive binding assays and solution hybridization assay. EGF-R-binding capacity and mRNA were demonstrated in a hormone-sensitive R3327 prostatic tumor from both control and castrated animals while no such activity was found in the hormone-independent AT-1 tumors. Castration induced no quantitative changes in the EGF-R. Estrogen treatment induced a significant reduction of the binding capacity of EGF-R and its mRNA. It was concluded that EGF-R is present in the androgen-sensitive Dunning prostatic tumor models (R3327), but that the androgen-insensitive, undifferentiated AT-1 tumor lacks EGF-R expression. Endocrine treatment has no significant effect on the EGF-R in these tumor models.

Effects of suramin on gastric mucosal ulceration, EGF and EGF-receptor content

1.1. The antiulcer activity (ethanol or indomethacin-induced ulcers) and the antisecretory effects (pylorus-ligated rats) of various selective and non selective calcium antagonists were studied.2.2. Flunarizine and pirenzepine reduce the ethanol-ulcer length whereas diltiazem and cimetidine are weakly active and verapamil, nifedipine and nicardipine are ineffective.3.3. All tested compounds except verapamil prevent the development of indomethacin-induced ulceration.4.4. All substances, except flunarizine decrease the total H+ output in Shay rats.5.5. The activities of the different compounds are discussed in terms of their mode of action.

Steroid-growth factor interaction in human prostate cancer. 1. Short-term effects of transforming growth factors on growth of human prostate cancer cells

In order to betweer define potential mechanisms of growth regulation in human prostate cancer cells, we have compared biological responses (such as short-term response to both transforming growth factor α and β; TFGα and TFGβ) in relation to hormone sensitivity of LNCaP, DU145, and PC3 cells. Androgen receptor (AR) and epidermal growth factor receptor (EGF-R) content of each cell line was also investigated. In addition, expression of EGF, TGFα, and TGFβ was evaluated through immunofluorescent staining. Growth of androgen non-responsive PC3 cells was stimulated by TGFα (about 35%) and inhibited by TGFβ more than 50%), with respect to controls, after 48h exposure. Conversely, AR-positive, hormone-responsive LNCaP cells proved to be poorly sensitive, at least short-term, to either growth factor. Furthermore, high levels of both EGF-R and TGFα, and a fairly high amount of EGF, were found in DU145 cells and, to a lesser extent, in LNCaP cells; in contrast, PC3 cells exhibited low expression levels of both receptors (EGF-R) and ligands (EGF, TGFα), but displayed remarkable TGFβ binding and relatively high levels of endogenous TGFβ. Overall, these results suggest a differential sensitivity to TGFα and TGFβ by prostate cancer cells; TGFα response seems not to be proportional to the EGF-R content of individual cell lines. (Steroids 59: 412–420, 1994)

Epidermal growth factor receptor content in human renal cell carcinomas.

The expression of epidermal growth factor receptor (EGFR) mRNA has been demonstrated in human renal cell carcinomas (RCC), but few reports quantitate EGFR in RCC and correlate EGFR content with clinicopathologic findings. Using 125I-EGF as a ligand, the maximum binding of EGF in membrane preparations from RCC (EGFR content) was studied by Scatchard analysis. A single class of binding sites for EGF was observed in 74% of RCC and 50% of normal renal tissues. The EGFR content was increased significantly in RCC compared with normal tissues. In all cases in which EGFR was undetectable, there was no evidence of distant metastasis, venous invasion, or regional lymph node involvement, and these patients had a better clinical outcome than patients with detectable EGFR. The EGFR content was significantly lower in nuclear Grade 1 tumors than in tumors of higher nuclear grades. No significant difference between EGFR content and other clinicopathologic findings was detected. The determination of EGFR content in RCC may become an important prognostic factor for the biologic behavior of RCC.

Hormone receptors and cathepsin D levels in human breast epithelial cells transformed by chemical carcinogens and c-Ha-ras transfection.

The objective of this work was to determine whether transformation of the human breast epithelial cell line MCF-10F by the chemical carcinogens 7, 12-dimethylbenz(a)anthracene (DMBA) or benzo(a)pyrene (BP), or c-Ha-ras oncogene transfection, influence the expression of epidermal growth factor receptor (EGFR), estrogen (ER) or progesterone (PR) receptors, and the content of cathepsin-D (Cath.D). MCF-10F control cells did not express any of the phenotypes of neoplastic transformation, whereas carcinogen-treated cells and clones derived from the latter formed colonies in agar-methocel, and exhibited increased chemotaxis and chemoinvasion. Clone BP-1E was also tumorigenic in SCID mice. The BP1 cell line transfected with mutated c-Ha-ras oncogene, named BP1-Tras, became more aggressive after transfection and decreased the latency time to tumorigenesis. Radioligand binding and immunocytochemical reactions were utilized for determining the receptors and Cath.D content of control and carcinogen-treated cells and their derived clones. MCF-10F cells contained 37 fmol/mg of protein of EGFR, ER and PR were undetectable, and Cath.D content was 70 fmol/mg protein. EGFR content was significantly higher in D3-1 and BP1-E cell lines vs the control MCF-10F and the other DMBA and BP clones, correlating positively with the emergence of the transformation phenotype. Whereas EGFR levels were not significantly different in BP1-Tras cells when compared with BP1-E, the former were more tumorigenic in SCID mice, an observation suggesting an alternative pathway in these cells in the formation of tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor content in normal and carcinomatous gastric and colonic tissue.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are polypeptides which bind to the EGF receptor (EGFr) and may play a role in cell growth and carcinogenesis. Our study investigated the content of EGF, TGF-alpha, and EGFr in tumors of the stomach and the colon in comparison with the surrounding mucosa. EGF was detected in half of the stomach specimens with concentrations between 1 and 9 ng/g weight irrespective of histology. In the colon no EGF was found in the tumor or normal mucosa. In the stomach normal mucosa contained higher TGF-alpha concentrations (mean 22.4 ng/g) than the tumors (mean 11.8 ng/g), but the difference was not statistically significant because of a wide variation in mucosal values. By contrast, the colon mucosa displayed significantly higher TGF-alpha concentrations than the tumor tissues (33 ng/g versus 12 ng/g; P < 0.01). EGFr content in the gastric mucosa was lower compared to gastric carcinoma (48 fmol/g versus 75 fmol/g) yet not significantly different. In contrast, colorectal tumor specimens disclosed significantly higher concentrations than the mucosal tissues (mean of 155 fmol/g versus 80 fmol/g; P < 0.01). In conclusion, TGF-alpha should not be considered a tumorigenic but a physiological growth factor in the stomach and colon. An elevated EGFr content in colorectal tumors in comparison with the normal mucosa could lead to a growth advantage by an autostimulating mechanism.

BIOCHEMICAL AND IMMUNOHISTOCHEMICAL DETECTION OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR (EGF-R) IN BREAST-TUMOR SPECIMENS

Analyses of the level of expression of the epidermal growth factor receptor (EGF-R) of breast cancer tumors may add independent information about the prognosis of individual patients. Furthermore, the use of monoclonal antibodies directed against EGF-R as therapeutic tools (e.g., Mab 425) requires a reliable evaluation of the individual EGF-R content. Various analytical methods have been published, including (Scarff RW and Torloni H: World Health Organization, Geneva, 1968), biochemical detection of EGF-R by a radiolabeled physiologic ligand [I-125]EGF, (Early Breast Cancer Trialists' Collaborative Group: Lancet 329: 1-15, 1992) biochemical analyses of EGF-R content with a monoclonal antibody, and (McGuire WL and Clark GM: N Engl J Med 326: 1756-1761, 1992) immunohistochemical EGF-R detection. We measured the EGF-R content in membrane pellets derived from routine processing for evaluation of estrogen (ER, ER-EIA) and progesterone receptor (PgR; PgR-EIA) in 185 breast cancers and 18 benign breast samples, using a single-point saturation assay (RBA). Simultaneously, ER (ER-ICA), PgR (PgR-ICA), and EGF-R immunohistochemistry was performed on frozen sections of the same tumors. Various cell lines and normal skin tissue samples served as EGF-R positive or negative controls. The results of the two different EGF-R analyzing methods were compared with other biological characteristics of the tumors. 37% of the tumors were EGF-R positive. There was an inverse correlation between the ER or PgR and the EGF-R content. EGF-R overexpression correlated with high tumor grade. Analyses of EGF-R content in membrane pellets of breast cancer samples by single point saturation assay as well as the evaluation of tumor sections by immunohistochemistry can be performed routinely. The results obtained with both analytical methods did not differ significantly. but the immunohistochemistry proved to be more difficult to perform and to interpret. Thus, we prefer to perform both analytical methods simultaneously to provide information potentially useful for clinical management of individual cancer patients.

Differential Immunoreactivity of Epidermal Growth Factor Receptor in Benign, Dysplastic and Malignant Prostatic Tissues

To investigate epidermal growth factor receptor (EGFr) presence in the prostate, monoclonal antibody (clone EGFR1) immunohistochemical examination of radical prostatectomy specimens was performed (n = 37). All prostatic specimens contained benign prostatic hyperplasia (BPH) and/or dysplasia (prostatic intraepithelial neoplasia or PIN), as well as prostatic carcinoma (CaP). Areas of dysplasia were further categorized as to the basal cell layer and the luminal cell area. BPH, PIN, and CaP tissues in each specimen were analyzed by a single observer and graded on a scale from 0–4+. Fifteen samples were also analyzed for EGFr content utilizing a Cell Analysis Systems (CAS 200) image cytometer.EGFr immunoreactivity of BPH basal cells was significantly higher than EGFr immunoreactivity in areas of CaP (p <0.001). EGFr staining of BPH basal cells was also significantly higher than that seen in PIN luminal cells (p <0.001). Immunoreactivity of EGFr in PIN basal cells was significantly higher than in PIN luminal cells (p <0.001). EGFr staining of basal cells in BPH tissues was higher than that seen in the PIN basal cell layer but the difference was not statistically significant (p = 0.06). The amount of staining present in PIN luminal cells was also significantly greater than in CaP tissues (p = 0.002).Quantitative image analysis utilizing the CAS 200 image cytometer was performed on BPH and CaP areas exclusively. EGFr immunoreactivity in basal cells of the BPH tissues was significantly greater than that seen in CaP tissues (p <0.001).The decreased EGFr immunoreactivity in CaP may reflect a differentiating role for EGFr in normal tissues. Loss of EGFr influence may be associated with an increased proliferative state in PIN and CaP. Destruction or alteration of the epidermal growth factor receptor by a protease, such as prostatic specific antigen, may also explain our findings. At the present time the meaning of the different amounts of EGFr in the various types of prostate tissues is unknown.

Measurement of human epidermal growth factor receptor in the endometrium during the menstrual cycle

To evaluate a potential physiologic role of the epidermal growth factor receptor in the endometrium, we measured the receptor content at different times in the menstrual cycle. Endometrial biopsy specimens were obtained from 28 normal women during the proliferative or secretory phase of the menstrual cycle, and the epidermal growth factor receptor content was determined. When the number of epidermal growth factor binding sites were evaluated as a function of time within each phase, a difference between phases became evident. The level of receptor increased during the proliferative phase with a maximum just before ovulation (p = 0.0128, r = 0.748). The epidermal growth factor receptor level decreased during the secretory phase, reaching a minimum before menses (p = 0.0001, r = 0.843). We conclude that the endometrial epidermal growth factor receptor content is cycle dependent, being maximal during the periovulatory period and minimal just before or during menses. These findings further suggest a physiologic role for epidermal growth factor in the proliferation and differentiation of the endometrium.

Progesterone Regulates Epidermal Growth Factor Receptor on Mucous Secreting Cells in the Rabbit Endocervix*

During postnatal differentiation, epidermal growth factor (EGF) receptor is expressed by all major cell types of the cervix. Computer-assisted image analysis confirmed the highest concentration of EGF receptor is in the epithelial cells. Flow cytometric analysis of subpopulations of epithelial cells from estrous rabbits showed the mucous secreting cells had the highest concentration of EGF receptor, i.e. 1-1.5 x 10(5) receptors per cell. Because the mucous secreting cells are targets for steroid hormones it seemed likely that steroids regulate EGF receptor expression. To investigate this possibility, hormone-dependent changes in EGF receptor expression were quantified by flow cytometry. Ovariectomy and the treatment of ovariectomized animals with estradiol altered forward angle light scatter and side scatter signals which correlated with cell size and secretory granule content, respectively. However, the number of epithelial cells and the number of EGF receptors per cell were unaffected. Progesterone treatment of ovariectomized animals dramatically reduced the number of EGF receptors on the mucous secreting cells, accounting for a 43% reduction in the total EGF receptor content of the epithelium. The treatment of neonates with diethylstilbestrol did not change the number of EGF receptors in endocervical epithelial cells when examined in adulthood. However, the number of mucous secreting cells was decreased, thereby reducing the EGF receptor content of the epithelium 19-36% compared to estrous and estradiol-treated animals. These results provide the first evidence that progesterone regulates EGF receptor on mucous secreting cells in the endocervix and that diethylstilbestrol treatment alters the EGF receptor content of the epithelium by altering its cellular composition.

Comparison of estrogen receptor and epidermal growth factor receptor content of primary and involved nodes in human breast cancer

Estrogen receptors (ER) and epidermal growth factor receptors (EGFR) in the tumor cells of breast cancer tissues (primary tumors) and metastatic lymph nodes (involved nodes) were analyzed by immunocytochemical study in 19 patients; 12 were ER positive, and seven were ER negative. Microscopic study was used to determine the percentage of positive cells and the staining index. The percentage of EGFR-positive cells and the EGFR staining index were higher in the ER-negative primary tumors than ER-positive primary tumors. In ER-positive cases, both the number of ER-positive cells and ER content per cell was less in the involved nodes than in the primary tumors, whereas the number of EGFR-positive cells and EGFR content per cell was greater in affected nodes. On the other hand, in the ER-negative cases the number of EGFR-positive cells and EGFR content per cell remain almost unchanged between the primary tumors and involved nodes. The authors supposed a probability, in this study, that estrogen may exert inhibitory action on EGFR production through binding to ER.

Density-Dependent Regulation of Epidermal Growth Factor Receptor Expression

Previous studies have demonstrated that binding of peptide growth factors such as epidermal growth factor (EGF) decreases as cell density increases. We now report that binding of EGF to MDA 468 breast carcinoma cells is reduced as cells increase in density with time in culture. Cells at low density bound more EGF per cell than cells at higher density. The reduction of EGF binding was due to a reduction in receptor number. Metabolic labeling of MDA 468 cells with [35S]-methionine followed by immunoprecipitation of the EGF receptor (EGFR) indicated that the amount of total receptor protein was decreased. Using RNA blot hybridization, we found that high-density cells contained decreased amounts of EGFR transcripts. Northern analysis revealed that both the 10- and 5.6-kilobase mRNA transcripts encoding the EGFR were decreased. These data suggest that increasing cell density with time in culture results in modulation of EGFR content, with changes at the level of both protein and mRNA expression.

Epidermal growth factor receptor status in four carcinoma of the cervix cell lines

We have evaluated aspects of the EGF receptor content of four human cell lines derived from patients with previously untreated carcinoma of the cervix. Scatchard analysis revealed that three of the lines possessed approximately 2×105 low-affinity and 2×104 high-affinity receptors, whereas the fourth line had approximately 9×104 low-affinity receptors and 9×103 high-affinity receptors. Immunocytochemical staining using the monoclonal antibody EGFR1 showed wide intra- and inter-line variation in staining intensity. Flow cytometric analysis of EGFR1 demonstrated a fivefold difference in staining intensity between lines. Thirteen cloned derivatives of one of the lines exhibited a 200% variation in EGFR1 staining intensity. There were no differences in radiosensitivity in four of the cloned lines with different EGF receptor levels. Southern blotting analysis did not reveal any rearrangement or amplication of the EGF receptor gene. These three different methods for determining receptor content produced variations in the ranking of receptor number across the four cell lines. These studies with cervix carcinoma cell lines demonstrate the presence of varied levels of EGF receptors according to the methodology used. This may reflect differences in biological characteristics of the cell lines evaluated.

Expression of epidermal growth factor receptor in normal colorectal mucosa, adenoma, and carcinoma

Using the monoclonal antibody EGF-R1, the expression of epidermal growth factor receptor (EGFR) was investigated immunohistochemically in normal colonic mucosa distant from and adjacent to colonic neoplasms, in 25 adenomas and in 144 unselected colorectal carcinomas. EGFR expression was an inconsistent phenomenon in each of these conditions. It was not expressed in 23/44 non-neoplastic mucosa specimens distant from and in 26/44 mucosae adjacent to colon tumours; 15/25 adenomas and 71 (49.3%) of the carcinomas failed to contain detectable amounts of EGFR. In contrast, large amounts of EGFR were found in 4 non-neoplastic mucosae at both locations, in 3 adenomas and in 11 (7.6%) carcinomas. The remaining cases showed complex patterns of EGFR-expression. In comparing mucosae close to and distant from a colonic tumour, only minor differences in EGFR content were observed. The intra-individual comparison of the mode of EGFR expression in non-neoplastic and neoplastic epithelium revealed an overexpression of EGFR in carcinomas in about one third of the 44 cases examined. One third showed no obvious differences, and one third showed lower levels of EGFR expression within the tumour. We conclude that the mode of EGFR expression in normal and neoplastic colon epithelium is variable and reflective of inter-individual constitutive differences rather than of abnormalities in gene regulation. Statistical analysis failed to reveal correlations between the mode of EGFR expression and tumour grade, type or Dukes stage.

Expression of human epidermal growth factor and its receptor in esophageal cancer

The expression of human epidermal growth factor (hEGF) was examined immunohistochemically in 86 esophageal cancer lesions, comprising 67 primary tumors and 19 metastatic lymph nodes. In the normal esophagus, the parabasal and intermediate cell layers showed a weak expression of hEGF, however, hEGF-positive tumor cells were detected in 62 (92.5 per cent) of the 67 primary esophageal carcinomas and in 18 (94.7 per cent) of the 19 metastatic lymph nodes. In this study, the immunoreactivity of hEGF was classified into 4 grades according to the number of stained tumor cells. A significant correlation was observed between the histologic type and the grade of hEGF immunoreactivity (Chi-square test, p less than 0.01). hEGF immunoreactivity in well differentiated squamous cell carcinomas was significantly higher than in other squamous cell carcinomas, although there were no correlations between other pathological findings and hEGF immunoreactivity. Patients with hEGF immunoreactivities of grades II or III had much worse prognoses than those with grades 0 or I (p less than 0.05). In 22 esophageal carcinomas and 10 normal esophageal mucosae, EGF receptor (EGFR) contents were measured by the competitive binding assay. The average EGFR content (101.3 +/- 35.7 fmol/mg protein, mean +/- SE) of the esophageal carcinomas was significantly higher than that (5.3 +/- 1.2) of the normal esophageal mucosae (p less than 0.05). Moreover, in hEGF negative tumors, EGFR contents were lower than in hEGF positive tumors. These results suggest that hEGF and EGFR show increased production in squamous cell carcinomas and could to be useful prognostic factors in patients with esophageal cancer.

Epidermal growth factor receptor and thyrotropin response in human thyroid tissues

The content of epidermal-growth-factor receptor (EGFr) and its relation to TSH-response were examined in 27 malignant thyroid tumors (5 follicular, 6 papillary, 5 medullary, 11 anaplastic carcinomas) and in 30 tumor-like lesions (21 hyperplastic goiters and 9 toxic adenomatous goiters). Normal 12 thyroid tissues adjacent to benign tumors with no evidence of macroscopic or microscopic abnormalities were used as control. All thyroid plasma membranes tested showed specific EGF binding. In membranes from toxic adenomas (2.18 +/- 0.73 fmoles/mg protein) and papillary carcinomas (2.80 +/- 0.80) the EGF binding was similar to that of normal thyroid membranes (2.32 +/- 0.73). Hyperplastic goiters showed an EGF binding (4.4 +/- 0.82) slightly higher than normal tissue. The highest and the lowest EGF binding values were found in anaplastic (11.8 +/- 2.78) and medullary (0.50 +/- 0.39) carcinomas, respectively. An inverse correlation between EGFr content and TSH-response was found when anaplastic thyroid tumors were compared to tumor-like lesions. However no correlation was observed in medullary carcinomas which also failed to respond to TSH and in papillary carcinomas which partially respond to thyrotropin.

Localization of human epidermal growth factor receptor in cervical intraepithelial neoplasias.

Immunohistochemical staining of epidermal growth factor receptor (EGF-R) with a monoclonal antibody was performed in 43 biopsies of cervical tissue. The distribution of the receptors in normal cervical tissue differs from that of cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma of the cervix. Whereas the staining reaction in normal squamous epithelium was confined to the basal and deep parabasal cell layer, in all cervical intraepithelial neoplasias, with or without human papilloma virus association, a homogeneous EGF-R staining reaction could be observed throughout the entire lesion. This means that the dysplasia cells of a CIN I-III, like the tumor cells of a squamous cell carcinoma, have a raised EGF-R content, which in the normal squamous epithelium is usually only found in the basal and deep parabasal cells that are capable of dividing. No EGF-R staining reaction could be detected in the higher, differentiated cell layers of the normal squamous epithelium of the cervix.