transforming-growth-factor-alpha and Adenocarcinoma--Papillary

There are no quantitative data on the mRNA expression of epidermal growth factor receptor (EGFR) and transformation growth factor alpha (TGF-α) in thyroid carcinoma. The aims of this study were to detect, quantify and analyse the clinicopathological correlations of the expression of these genes in a large cohort of patients with thyroid carcinoma.. EGFR and TGF-α expression were investigated using real time quantitative polymerase chain reaction and immunohistochemistry on 71 papillary thyroid carcinomas (PTCs), 68 paired non-cancer thyroid tissues adjacent to the PTC and 20 benign thyroid lesions.. TGF-α and EGFR mRNA increased in PTC when compared with benign thyroid lesions. In many PTCs with high level of expression of TGF-α and EGFR mRNA, the morphological non-cancer tissue adjacent to the cancer also showed high levels of expression of these mRNAs. The levels of expression of mRNA of TGF-α and EGFR correlated with each other and with the level of protein expression. The level of expression of TGF-α mRNA was significantly related to lymphovascular permeation while the expression of EGFR mRNA was related to the pathological subtype of PTC and cancer recurrence.. TGF-α and EGFR were overexpressed, correlated with each other and associated with the pathological parameters in papillary thyroid carcinoma. The results provide information for management of thyroid cancer in the era of gene targeting therapy.

Topics: Adenocarcinoma, Papillary; Adolescent; Adult; Aged; Aged, 80 and over; Child; ErbB Receptors; Female; Fluorescent Antibody Technique, Indirect; Gene Expression; Humans; Immunoenzyme Techniques; Lymphatic Vessels; Male; Middle Aged; Prognosis; RNA, Messenger; Thyroid Gland; Thyroid Neoplasms; Transforming Growth Factor alpha; Young Adult

The clear cell and the papillary types of human renal cell carcinoma (RCC) are distinct tumour entities with marked differences in their biological properties. Because growth factors are considered to affect profoundly the biological behaviour of malignant tumours, we compared the expression and function of transforming growth factor (TGF)-alpha and fibroblast growth factor (FGF) in both types of RCCs. Both in vivo and in vitro expression of TGF-alpha, epidermal growth factor-receptor (EGF-R), FGF-2 and FGF type 3- and 4-receptors was found in RCCs of both types. However, marked differences between clear cell and papillary RCCs became evident for TGF-alpha secretion, which could be demonstrated in 20 out of 24 (83%) clear cell RCCs but in only two out of four (50%) papillary tumours. Moreover, the mean TGF-alpha secretion rate in clear cell RCCs significantly (P<0. 05) exceeded that of papillary RCCs. Because the expression of growth factor receptors could not prove the corresponding signalling cascades were functional, tumour cell proliferation was tested after exposure to exogenous TGF-alpha or FGF-1. These experiments demonstrated that papillary RCCs did not respond significantly to exogenous TGF-alpha or FGF-1, whereas eight (33%) (TGF-alpha) and 11 (46%) (FGF-1) out of 24 clear cell RCCs responded with significant (P<0.05) growth stimulation. In conclusion, our investigation presents data indicating that TGF-alpha and FGF are functionally involved in the progression of clear cell RCCs, directly stimulating proliferation by autocrine and/or paracrine actions. In contrast, TGF-alpha and FGF did not directly stimulate the proliferation of our papillary RCCs, thereby suggesting functional defects or a blockade in the corresponding signalling cascades. This differential functionality might contribute to the more aggressive behaviour of clear cell RCCs.

Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Papillary; Blotting, Northern; Carcinoma, Renal Cell; Fibroblast Growth Factors; Flow Cytometry; Humans; Immunohistochemistry; Kidney Neoplasms; Receptors, Fibroblast Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; Transforming Growth Factor alpha; Tumor Cells, Cultured

Transforming growth factor alpha (TGF alpha) expression was analyzed immunocytochemically on formalin-fixed wax-embedded sections obtained from 24 benign prostatic hyperplasia (BPH) specimens and 76 prostatic carcinoma tissues, 3 human prostatic tumor xenografts, normal kidney, and salivary gland. Low amounts of TGF alpha immunopositivity were encountered in the epithelium of BPH glandular tissues, whereas in the prostatic adenocarcinoma samples, a greater heterogeneity and intensity of TGF alpha immunostaining was observed. The most intense staining was exhibited by the least differentiated tumors, although a few of these were weakly stained. Statistical analysis of the relationship of histopathological grade of tumor with TGF alpha expression in the carcinomas showed a significant correlation of these parameters, 0.01 > P > 0.001. The expression of the proliferation markers Ki-67 and PCNA was also analyzed in the carcinoma specimens, and the relationship of these to TGF alpha expression indicated that there was no significant correlation in this series of tumors between increased growth activity and TGF alpha expression (p approximately 0.25 with both markers). The prostatic carcinoma xenografts TEN12 and TEN15 contained low levels of immunoreactive TGF alpha, which was uniformly distributed, whilst heterogeneous immunostaining was observed in the uroepithelial xenograft TEN16. In the normal human kidney, TGF alpha was concentrated in the epithelium of the distal convoluted tubules (DCT) and the collecting tubules (CT), and lower amounts were identified in the proximal convoluted tubules (PCT). As in the prostatic carcinomas, the immunostaining was eliminated by prior absorption of the antibody with pure TGF alpha and not with human or mouse EGF. No crossreactivity of the TGF alpha antibody with salivary EGF was demonstrated. This study concludes that, in prostate carcinoma, the least differentiated tumors more often expressed greater amounts immunoreactive TGF alpha; however, no relationship between TGF alpha expression and cellular proliferation markers was found.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Animals; Antigens, Neoplasm; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Ki-67 Antigen; Kidney; Male; Mice; Mice, Nude; Neoplasm Proteins; Neoplasm Transplantation; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Submandibular Gland; Transforming Growth Factor alpha