Patterns of expressions of transforming growth factor and epidermal growth factor receptor in squamous cell lesions of the urinary bladder

Abstract

Aim-To investigate the patterns of expression of transforming growth factor (TGF-) and epidermal growth factor receptor (EGFR) in squamous metaplasia and squamous cell carcinomas of the urinary bladder with and without schistosomiasis. Methods-Immunohistochemical study of the expression of TGF-and EGFR in squamous metaplasias (n = 12) and various grades of squamous cell carcinomas (n = 21) of the bladder with and without schistosomiasis. Results-Focal cytoplasmic and membranous positivity for EGFR and TGF-was seen in all cases of squamous metaplasia. The markers were diVusely coexpressed in a concordant pattern in areas of hyperplastic keratinising squamous metaplasia. A similar pattern of positivity was seen in verrucous carcinomas (n = 2) and well diVerentiated squamous carcinomas (n = 6). Progressive loss of diVerentiation was associated with increasing loss of EGFR staining while TGF-staining was retained. Squamous cell carcinoma in situ (n = 2) showed focal positivity for TGFand EGFR. There were no diVerences in staining patterns between cases with and without schistosomiasis. Conclusions-The coexpression of TGFand EGFR by well diVerentiated squamous cell carcinomas and hyperplastic keratinising squamous metaplasia is consistent with the active regulatory role exerted by this autocrine loop. There is regional absence of expression of EGFR but not of TGF-in squamous cell carcinomas of lesser diVerentiation, suggesting heterogeneity of such control in these tumours. The focal expression of the two markers in squamous cell carcinomas in situ indicates a possible second pathway of oncogenesis for less diVerentiated tumours. These observations may have important implications for the eVectiveness of putative growth factor based treatments. (J Clin Pathol 1998;51:583-587)

Deletions of p15 and p16 in schistosomal bladder cancer correlate with transforming growth factor-α expression

“…previous report[27], a similar pattern was observed for overexpression of TGF-a in SCC (72.1%) compared to TCC (28.8%). It is possible that cases with the SCC component are more genetically unstable and had alterations not present in TCC cases.…”

Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic

“…Another important confounding factor that had been reported to increase the TGF-α expression is the presence of urinary infection (Tungekar and Linehan, 1998). In our studies this was evaluated as a categorical variable measuring the presence of leukocytes in urine by a semiquantitative technique.…”

Prophylactic Radical Cystectomy for the Management of Keratinizing Squamous Metaplasia of the Bladder in a Man With Tetraplegia

“…Although the exact pathophysiology underlying the transformation from keratinizing squamous metaplasia to squamous cell carcinoma is unknown, several etiologic factors have been linked its development (1,15). Chronic inflammation caused by indwelling catheters and stones, as well as infection secondary to parasites, are considered to be the most likely etiologic agents (1,3,4,8,12,13).…”

“…However, because of limited data on these types of protocols, no approach can be considered superior (1,2,10), and some have been proven ineffective (1,6,7). Most recently, some authors have suggested that EGFR could potentially be used as logic therapeutic target for keratinizing squamous metaplasia, among other bladder lesions, that are difficult to manage clinically (4,15). However, some investigators advocate for a more aggressive management with radical bladder resection to avoid development of malignant transformation (1,3,(5)(6)(7).…”