transforming-growth-factor-alpha and Uterine-Cervical-Dysplasia

In women with CIN at fertile age and those over 50 years of age, EGFR expression is lower in the presence of Chlamydia trachomatis (Cht) infection. In all Cht infected women over 50 years of age expression of Ki 67 is higher; the increase is significant among women with invasive carcinoma. In these groups of women with CIN and invasive carcinoma TGF-alpha expression is insignificantly augmented. Chronic Cht infection is associated with cervical hypertrophy.

Topics: Adult; Age Factors; Chlamydia Infections; Chlamydia trachomatis; DNA Primers; ErbB Receptors; Female; Hormones; Humans; Immunohistochemistry; Ki-67 Antigen; Middle Aged; Neoplasm Staging; Papillomaviridae; Polymerase Chain Reaction; Transforming Growth Factor alpha; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

We analyzed 149 women (81 with cervical intraepithelial neoplasia and with invasive carcinoma of the cervix and 68--as a control group). The influence of Chlamydia trachomatis (Cht) infection into expression of EGFR, TGF-alpha, Ki 67, HPV 16 and 18 was examined. IS-PCR was used to measure the level of antibodies in the serum. We detected that chlamydial infection may cause cervical hypertrophy in women with and without cervical intraepithelial neoplasia and invasive carcinoma. Infections of both Cht and HPV correlate with high expession of Ki 67 in epithelium. Cht infection also increased the expression of HPV16 in CIN I. These results suggest that Cht infection modifies the activity of viruses. In our research we have confimed that Cht infection increases the expression of EGFR and TGF-alpha. These facts may explain variants other than the HPV-mechanism of cervical carcinogenesis.

Topics: Adult; Antibodies, Bacterial; Carcinoma; Case-Control Studies; Chlamydia Infections; Chlamydia trachomatis; Epidermal Growth Factor; Female; Humans; Ki-67 Antigen; Middle Aged; Neoplasm Invasiveness; Papillomaviridae; Polymerase Chain Reaction; Transforming Growth Factor alpha; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Expression of epidermal-growth-factor receptor (EGFR), transforming growth factor alpha (TGF-alpha) and Ki-67 proliferation antigen in cervical intra-epithelial neoplasms were analyzed. To examine the interrelationship of TGF-alpha, EGFR, Ki-67 and HPV status in dysplasia and carcinoma in situ, formalin-fixed tissue sections of 92 women were immunostained with monoclonal antibodies to EGFR, TGF-alpha and Ki-67. The presence of HPV was assessed by in situ DNA hybridization. The highest positive TGF-alpha expression was seen in the group of mild dysplasia. The difference was significant between the relatively high expression in mild dysplasia and the low occurrence in severe dysplasia and carcinoma in situ as well. The same relation could be found between TGF-alpha expression in papilloma-virus-negative dysplasia and those with the presence of HPV 16/18. In contrast to these findings, the Ki-67 proliferation marker was intensely detectable in severe dysplasia and carcinoma in situ. Ki-67-stained neoplastic cell nuclei were found in a significantly higher percentage of HPV-positive than in HPV-negative lesions. TGF-alpha over-expression is obviously combined with low proliferating activity and vice versa. Irrespective of the grade of dysplasia or HPV status, EGFR was expressed abnormally as compared with normal squamous epithelium. Over-expression of TGF-alpha in mild dysplasia could be associated with the autocrine pathway of cell-growth regulation. In the presence of HPV 16/18 the EGFR/TGF-alpha pathway for growth stimulation is probably not involved.

Topics: Carcinoma in Situ; Cell Division; ErbB Receptors; Female; Humans; Immunohistochemistry; Ki-67 Antigen; Neoplasm Proteins; Nuclear Proteins; Papillomaviridae; Transforming Growth Factor alpha; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Reverse transcription polymerase chain reaction (RT-PCR) revealed that the Fallopian tubes express epidermal growth factor (EGF), transforming growth factor (TGF alpha), and EGF receptor (EGF-R) mRNA. The RT-PCR product was verified by restriction enzyme digestion analysis. Immunohistochemically, EGF, TGF alpha, and EGF-R were localized in Fallopian tubes by use of specific antibodies to human EGF, mature fragments of human TGF alpha, and monoclonal antibodies to the extracellular binding domain of EGF-R. The tubal epithelial cells were the primary site of immunoreactive EGF, TGF alpha, and EGF-R, which were present to a lesser extent in the stromal cells, smooth muscle cell layers, fibroblasts of serosal tissue, and arterial endothelial and smooth muscle cells. Using antibodies generated against the amino and carboxy termini of TGF alpha precursor produced a similar cellular distribution to that observed for mature TGF alpha. The intensity of immunoreactive TGF alpha with these antibodies was similar to that seen with EGF. The ciliated and nonciliated epithelial cells in the ampullary and isthmus regions immunostained with similar intensity for EGF, TGF alpha, and EGF-R. The immunostaining for EGF, TGF alpha, and EGF-R was cycle-dependent, was considerably higher during late proliferative and early-to-mid-secretory phases than during early proliferative and late secretory phases of the menstrual cycle, and was reduced during the postmenopausal period. Specimens obtained 5-12 yr after tubal ligation immunostained for EGF, TGF alpha, and EGF-R similarly to sections from unligated tubes taken during the same phase of the cycle. Quantitative autoradiography of 125I-EGF binding generated a pattern similar to that of immunostaining for EGF-R binding. Net grain density/100 microns 2 calculated for different cell types indicated that the epithelial cells had a significantly higher grain density than did other tubal cell types (p < 0.05) without the cycle dependency seen in the immunohistochemical study. In summary, the results demonstrate that the human Fallopian tube expresses mRNA and contains immunoreactive proteins for EGF, TGF alpha, and EGF-R as well as binding sites for 125I-EGF. The cycle dependency and lower immunostaining in postmenopausal tubes suggest a potential regulation of their expression by ovarian steroids. The results imply the importance of EGF/TGF alpha in a variety of tubal biochemical and physiological functions and possibly early embryon

Topics: Autoradiography; DNA Restriction Enzymes; Endothelium, Vascular; Epidermal Growth Factor; ErbB Receptors; Fallopian Tubes; Female; Gene Expression; Humans; Immunohistochemistry; Male; Muscle, Smooth; Ovarian Neoplasms; Polymerase Chain Reaction; Pregnancy; RNA, Messenger; Transforming Growth Factor alpha; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms