transforming-growth-factor-alpha and Laryngeal-Neoplasms

To elucidate the stimulating role of the growth factor autocrine loop in the carcinogenesis and development of laryngeal carcinomas.. The reverse transcription-polymerase chain reaction technique was applied, and with beta-actin as internal standard, TGF-alpha and EGFR mRNA in laryngeal carcinomas, macroscopically normal laryngeal mucosas adjacent to the tumor and in vocal cord polyps were quantitatively examined.. The mRNA index of both TGF-alpha and EGFR in laryngeal carcinomas and adjacent mucosas was significantly higher than those in vocal cord polyps (P < 0.05). The index of TGF-alpha mRNA was significantly higher in laryngeal carcinomas than in mucosas adjacent to the tumor (P < 0.05).. The autocrine system consisting of TGF-alpha and EGFR may play an important role in the very early stage of laryngeal carcinoma, or even when the tissue phenotypic alteration does not occur. The elevated TGF-alpha mRNA level may trigger a switch from genotypic alteration to the phenotypic. The results are expected to be a theoretical basis for the preventive chemotherapy of laryngeal carcinomas.

Topics: Carcinoma, Squamous Cell; ErbB Receptors; Humans; Laryngeal Neoplasms; RNA, Messenger; Transforming Growth Factor alpha

The purpose of this study was to determine the overexpression of both epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) (a ligand of EGFR) in early laryngeal squamous cell carcinoma. In addition, we attempted to evaluate the prognostic values of our findings. Expression of EGFR and TGF-alpha in tumor tissue was examined immunohistochemically in 68 patients who had been treated with radiotherapy for early laryngeal cancer. Overexpression of the two factors was noted in 42.6% and 55.9%, respectively. No significant differences due to age, tumor size, and location or grade of cancer tissues were seen. Higher survival rates, found in patients with EGFR (-) and TGF-alpha (-) tumors as compared with those with EGFR (+) and TGF-alpha (+) (97.4%, 100% and 86.2%, 86.8%, respectively), were not statistically significant. The recurrence rates were similar between EGFR (+) and EGFR (-) (37.9% and 35.9%, respectively). However, the recurrence rate in patients with TGF-alpha (+) was significantly higher (57.9%) than in those with TGF-alpha (-) (10%; P<.01). Therefore overexpression of TGF-alpha may be an important indicator for recurrence in patients with early laryngeal squamous cell carcinoma treated by irradiation.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; ErbB Receptors; Female; Humans; Immunohistochemistry; Laryngeal Neoplasms; Male; Middle Aged; Prognosis; Survival Rate; Transforming Growth Factor alpha

Transforming growth factor alpha (TGF-alpha) is a polypeptide that is structurally similar to epidermal growth factor (EGF) that binds to the epidermal growth factor receptor (EGFR) and has been implicated in the development of several types of human tumours.. The expression of TGF-alpha is examined in laryngeal squamous cell carcinoma (SCC) (n = 24) and non-neoplastic polyps (n = 7) using streptavidin-biotin immunohistochemistry and a monoclonal antibody to the TGF-alpha protein. These cases had been previously characterized for EGFR immunoreactivity. The carcinomas were classified as well differentiated (n = 2), moderately differentiated (n = 16) and poorly differentiated (n = 6). Tissues from metastatic tumour deposits in lymph nodes (n = 5) were also studied.. TGF-alpha overexpression was defined as intense immunoreactivity in more than two-thirds of tumour cells immunostained for TGF-alpha and was present in the majority of the SCC cases (n = 15; 63%) and metastatic tumour deposits (n = 4; 80%). In contrast, although some of the vocal cord polyps showed weak (n = 2) to moderate (n = 5) immunostaining, none had evidence of strong TGF-alpha immunoreactivity. The differences in TGF-alpha immunoreactivity were significant between primary laryngeal SCC and vocal cord polyps (P = 0.013; chi 2 test with continuity correction), and between metastatic laryngeal SCC and vocal cord polyps (P = 0.023; chi 2 test with continuity correction). There was no significant difference in TGF-alpha expression between the different grades of carcinomas (P = 0.92, chi 2 test) or between non-metastatic and metastatic carcinomas (P = 0.82; chi 2 test with continuity correction). No significant correlation was found between TGF-alpha expression and patient survival or tumour recurrence (r = 0.077, r2 = 0.006, P = 0.75; simple regression analysis), or between TGF-alpha expression and EGFR immunoreactivity (r = 0.325, r2 = 0.106, P = 0.0851).. In conclusion, increased TGF-alpha immunoreactivity is present in most cases of laryngeal SCC with no specific relationship to tumour grade, suggesting that it may be important in the development of laryngeal carcinomas but not in its progression. No significant correlation was found between TGF-alpha and EGFR expression in laryngeal tumours and TGF-alpha immunoreactivity is of no prognostic value.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; ErbB Receptors; Female; Humans; Immunohistochemistry; Laryngeal Neoplasms; Male; Middle Aged; Polyps; Prognosis; Regression Analysis; Transforming Growth Factor alpha; Vocal Cords

A case of synchronous squamous cell carcinomas in the soft palate, larynx and esophagus is reported, along with findings of molecular-pathological analysis. A biopsy sample from the aryngeal carcinoma revealed well differentiated squamous cell carcinoma harboring two point mutations at codons 144 and 148 of the p53 gene but not at codon 299, and more than 50% of the cancer cells showed accumulation of p53 protein immunohistochemically. The esophageal tumor, which was moderately differentiated squamous cell carcinoma, showed immunoreactivity for p53 within the nuclei of 25-50% of cancer cells with a missense mutation at codon 299 but not at codon 144 or 148. This cancer also showed immunoreactivity for transforming growth factor alpha. On the other hand, the poorly differentiated squamous cell carcinoma in the soft palate showed negative immunoreactivity for p53 and no point mutation in exons 5 to 8 of the gene. These results suggest that the three synchronous squamous cell carcinomas arose as independent events.

Topics: Aged; Carcinoma, Squamous Cell; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Genes, p53; Humans; Immunohistochemistry; Laryngeal Neoplasms; Male; Mutation; Neoplasms, Multiple Primary; Palatal Neoplasms; Palate, Soft; Polymerase Chain Reaction; Stomach Neoplasms; Transforming Growth Factor alpha; Tumor Suppressor Protein p53

Fifteen laryngeal squamous cell carcinomas were investigated for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) using immunohistochemical methods. In a recent study the same material was characterized for epidermal growth factor receptors (EGF receptors) which were confined predominantly to the undifferentiated cells. The expression of this growth factor system in malignant cells may play a role in carcinogenesis and/or tumour growth. All carcinomas were positive for TGF-alpha and 12 were positive for EGF. In moderately-to-well differentiated carcinomas, the immunoreactivity was mainly detected in the cytologically more differentiated cells. Nine sections included both laryngeal stratified squamous epithelium of normal appearance and carcinoma. The immunoreactivity was here again localized in the cytologically more differentiated cells above the basal cell layer. The present investigation and our previous results confirm the existence of EGF receptors, TGF-alpha and EGF in laryngeal carcinomas. In addition, we conclude that the conditions do exist for growth factors to act through an autocrine system in poorly differentiated tumours and through a paracrine system in the moderately-to-well differentiated tumours.

Topics: Carcinoma, Squamous Cell; Cell Differentiation; Cytoplasm; Endothelium; Epidermal Growth Factor; Epithelium; Exocrine Glands; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Muscles; Laryngeal Neoplasms; Macrophages; Male; Mucins; Neoplasm Staging; Transforming Growth Factor alpha

Altered expression of growth factors and growth factor receptors is frequently described in human tumors and human tumor cell lines. This further supports the hypothesis that oncogenesis is due to the subversion of mitogen-responsive pathways. The aim of this study was to investigate the expression of epidermal growth factor receptor (EGFR) and transforming growth factor alpha (TGF alpha) in 13 larynx carcinomas and 2 carcinomas of the oral cavity. We found receptor overexpression in 7 out of 15 tumors at mRNA and/or protein level but low expression in the majority of the normal adjacent tissues. TGF alpha was expressed only in 1 case, but no tyrosine kinase activity of the receptor was detected by antiphosphotyrosine antibody.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; ErbB Receptors; Humans; Immunoblotting; Laryngeal Neoplasms; Middle Aged; Mouth Neoplasms; RNA, Messenger; RNA, Neoplasm; Transforming Growth Factor alpha