Immune detection of neuron specific enolase and human chorionic gonadotropin in some cases of high grade transitional cell carcinoma of the urinary bladder

ABSTRACT

One third of the cases of transitional cell carcinoma [TCC] ectopically produce trophoblastic hormones, which is specifically correlated with the stage and grade of the tumour. The larger clinical studies have shown that human chorionic gonadotrophin [HCG] expression correlates with tumours of poor prognosis, which subsequently metastasize or fail to respond to radiotherapy. Expression of neuron specific enolase [NSE] as a marker of neuroendocrine differentiation was not only observed in small cell carcinoma of the bladder, but also in advanced cases of TCC, though it was neither correlated significantly to grade or stage of malignancy. The material of the present work included 20 cases of TCC of different grades, all were retrospective cases obtained from the files of the Pathology Department, Faculty of Medicine, Alexandria University. Representative sections from the formalin-fixed paraffin blocks were cut into thin sections of about 5 microns thick, and examined by H and E stain to determine the grade of the tumour as well as its stage of invasion. Chosen sections were mounted on coated slides for immunohistochemical staining using anti-beta hCG and NSE using streptavidine biotin complex technique, followed by semi-quantitative assessment of immunohistochemically positive cells. Histopathologic examination of the included cases using Hand E revealed that 10 cases exhibited papillary pattern, whereas 10 other cases were of non-papillary pattern. One case was considered as papillary urothelial neoplasm of low malignant potential [PUNLMP], 2 cases were of grade I, 3 cases were of grade II, and 14 cases were of grade III. Multinucleated giant cells were encountered in 4 cases of high grade TCC Two cases were superficial papillary tumours [pTa], 6 cases were invading the lamina propria [p T 1] and 12 cases were invasive tumours [p T 2-4]. Immunohistochemical staining for HCG-beta revealed 11 positive cases [55%] and 9 negative cases [45%]. About 10 of the positively stained cases [71.4%] were of high grade carcinomas versus one positive case [16.7%] of low grade carcinoma [P = 0.024 asterisk]. Immunohistochemical staining by NSE revealed 4 positive cases [20%] appeared as focal brown cytoplasmic staining, all detected in poorly differentiated high grade carcinomas [grade III]. No significant correlation was seen between reaction to HCG and NSE staining [p = 0.53]. In the present study positive immunoreactivity to hCG was seen in the poorly differentiated high grade urothelial tumours [10 cases of grade III and one case of grade II], whereas almost all the tumours categorized as papillary urothelial neoplasm of low malignant potential [PUNLMP], all grade I cases and 2 out of 3 cases of grade II urothelial carcinomas were negatively stained. i. e, reaction to HCG was significantly correlated to the grade of carcinoma [p = 0.024 asterisk]. Similarly, the intensity of staining of the cytoplasm increased significantly with the increase of the grade of the tumour [p= 0.031 asterisk] as well as the stage of infiltration [p = 0.0005 asterisk]. in the present study, where only 4 cases out of 20 [20%] of the included cases[all were of grade III] were positively stained by NSE