transforming-growth-factor-alpha and Condylomata-Acuminata

Epithelial growth factor receptor (EGFR) sends signals to the proliferation signal transduction system, receiving two ligands: epithelial growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). This immunohistochemical study examined the roles of EGFR and its ligands in the proliferation of normal and neoplastic vulvar squamous cells in 25 patients with vulvar squamous cell carcinoma (VSCC), 10 patients with vulvar condyloma acuminata (VCA), 15 patients with vulvar intra-epithelial neoplasm I-II or III (VIN I-II or III), and 5 subjects with vulvar normal squamous cells (VNSC). EGFR was detected in a few basal cells in 40% of the VNSC, in highly dysplastic cells in 40% of the VIN III, in many neoplastic cells in 80% of the VCA, and in some malignant cells in 64% of the VSCC. EGF was seen in the cytoplasm in 20% of the VIN I-II, 100% of the VIN III, 100% of the VCA, and 100% of the VSCC. Diffuse TGF-alpha was weakly expressed in the cytoplasm in 100% of the VNSC, more intensely in 100% of the VIN and 100% of the VCA, and intensely in 100% of the VSCC. These findings led to the suggestion that the TGF-alpha-EGFR system maintains the growth of normal squamous cells and, in part, maintains the growth of dysplastic and neoplastic squamous cells in the vulva. EGF expression was an early sign of neoplasia. The expression of EGFR with overexpression of its two ligands contributed to the proliferation of dysplastic and neoplastic squamous cells in VIN III and VCA. EGFR expression appeared to contribute to essential neoplastic abnormalities in 64% of the VSCC.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Condylomata Acuminata; DNA, Viral; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Immunohistochemistry; Ligands; Papillomaviridae; Papillomavirus Infections; Transforming Growth Factor alpha; Tumor Virus Infections; Vulva; Vulvar Neoplasms

To investigate the expression and distribution of transforming growth factor-alpha (TGF-alpha) in the normal cervix and in benign and malignant lesions of the uterine cervix.. Immuno-histochemical reactivity with a monoclonal antibody against TGF-alpha was examined in tissue specimens from 15 normal cervices, six cervical polyps, four cervical condylomata acuminata, 34 cervical intra-epithelial neoplasias, 35 invasive squamous cell carcinomas, five adenocarcinomas, and three mixed adenosquamous carcinomas.. Normal squamous cells of the exocervix were found to be negative for TGF-alpha immunoreactivity, whereas reserve cells and metaplastic squamous cells in the transformation zone were positive for TGF-alpha. Although TGF-alpha immuno-reactivity was variable in the cervical condylomas, most cases of cervical intra-epithelial neoplasia with or without koilocytotic atypia were negative for TGF-alpha. In the invasive carcinomas, however, TGF-alpha immuno-reactivity was observed in 17 out of the 35 cases of squamous carcinoma, and in all cases of adeno- and adenosquamous carcinomas. In addition, intense TGF-alpha immuno-reactivity was found in clinically advanced tumours.. These results suggest that the expression of TGF-alpha is associated with squamous metaplasia in the normal cervix, and that TGF-alpha may play an important role in cervical carcinogenesis, especially in its progression.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Cervix Uteri; Condylomata Acuminata; Female; Humans; Immunohistochemistry; Neoplasm Staging; Polyps; Transforming Growth Factor alpha; Uterine Cervical Neoplasms