Tungekar M F, Linehan J
Histopathology Department, St Thomas' Hospital (United Medical and Dental School), London, UK.
J Clin Pathol. 1998 Aug;51(8):583-7. doi: 10.1136/jcp.51.8.583.
To investigate the patterns of expression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) in squamous metaplasia and squamous cell carcinomas of the urinary bladder with and without schistosomiasis.
Immunohistochemical study of the expression of TGF-alpha and EGFR in squamous metaplasias (n = 12) and various grades of squamous cell carcinomas (n = 21) of the bladder with and without schistosomiasis.
Focal cytoplasmic and membranous positivity for EGFR and TGF-alpha was seen in all cases of squamous metaplasia. The markers were diffusely 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 differentiated squamous carcinomas (n = 6). Progressive loss of differentiation was associated with increasing loss of EGFR staining while TGF-alpha staining was retained. Squamous cell carcinoma in situ (n = 2) showed focal positivity for TGF-alpha and EGFR. There were no differences in staining patterns between cases with and without schistosomiasis.
The coexpression of TGF-alpha and EGFR by well differentiated 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-alpha in squamous cell carcinomas of lesser differentiation, 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 differentiated tumours. These observations may have important implications for the effectiveness of putative growth factor based treatments.
研究转化生长因子α（TGF-α）和表皮生长因子受体（EGFR）在伴有或不伴有血吸虫病的膀胱鳞状化生及鳞状细胞癌中的表达模式。
采用免疫组织化学方法研究伴有或不伴有血吸虫病的膀胱鳞状化生（n = 12）及不同分级的鳞状细胞癌（n = 21）中TGF-α和EGFR的表达。
在所有鳞状化生病例中均可见EGFR和TGF-α的局灶性胞质和膜阳性。在增生性角化鳞状化生区域，这些标志物呈弥漫性共表达，且表达模式一致。在疣状癌（n = 2）和高分化鳞状细胞癌（n = 6）中也观察到类似的阳性模式。分化程度的逐渐降低与EGFR染色的逐渐缺失相关，而TGF-α染色得以保留。原位鳞状细胞癌（n = 2）显示TGF-α和EGFR呈局灶性阳性。伴有和不伴有血吸虫病的病例之间染色模式无差异。
高分化鳞状细胞癌和增生性角化鳞状化生中TGF-α和EGFR的共表达与该自分泌环发挥的积极调节作用一致。在低分化鳞状细胞癌中存在EGFR表达缺失但TGF-α表达未缺失的区域，提示这些肿瘤中这种调控存在异质性。原位鳞状细胞癌中这两种标志物的局灶性表达表明低分化肿瘤可能存在第二条肿瘤发生途径。这些观察结果可能对基于生长因子的假定治疗的有效性具有重要意义。
