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Abstract
Transitional Cell Carcinoma (TCC) of the urinary bladder is one of the most frequently diagnosed human neoplasms in the world. In Egypt carcinoma of the urinary bladder is the most prevalent cancer, the median age at diagnosis is 46 years, with a male preponderance of 5:1.
The development of TCC of the urinary bladder seems to depend on a combination of genetic and environmental factors. Among the latter, chemical factors are thought to be of great importance (e.g. exposure to petrochemicals, cigarette smoke and aniline dyes). Also there is a slight increased risk for the development of urinary bladder carcinomas in patients who had been previously treated with radiation therapy. Schistosoma haematobium infection is also thought to be pathogenetically related to the development of TCC of the urinary bladder.
Prognosis and therapy of TCC depends on the pathological stage (including lymph node involvement) and grade, but as yet there is no reliable tumor marker for its early detection, diagnosis, identification of progression, or follow-up.
The aim of the present study was to assess immunohistochemically the trophoblastic hormone (hCG) production profile of TCC of the urinary bladder and correlate histological differentiation and tumor stage with marker expression.
The present study included forty cases of TCC of the urinary bladder (twenty were retrospective cases and twenty prospective). The formalin fixed paraffin embedded blocks of these cases were collected from the files of the Pathology Department, Faculty of Medicine, Alexandria University and the Pathology Department of Damanhour Oncology Centre.
The formalin fixed, paraffin embedded tissue blocks from all the studied specimens were sectioned and stained with H&E (to determine their histological grade and tumor stage). Special staining using Masson’s trichrome were performed for better identification of muscle invasion. Immuno-histochemical staining with Anti β-hCG was done using the avidin-biotin technique. Positive reaction was indicated by brown granular cytoplasmic staining of the malignant cells.
Patients’ age ranged from 40 to 78 years with a mean of 60.95 ± 9.77 years. There were twenty-six males (65%) and fourteen (35%) females. Twenty-three (57.5%) of tumors were papillary and seventeen (42.5%) were non papillary. Three cases (7.5%) were PUNLMP, four (10%) grade 1, ten (25%) grade 2 and twenty-three (57.5%) grade 3. Multinucleated tumor giant cells (syncytiotrophoplastic-like giant cells) were detected in six cases (15%) and also squamoid differentiation in six (15%) tumors. Twenty (50%) out of the forty cases examined were superficial tumors, of which three (15%) were non invasive papillary (pTa) and seventeen (85%) invaded the suburothelium (pT1), and twenty (50%) were invasive (pT2-4). Ten cases (25%) were associated with metastases (only nodal ”9” and distant”1”).
An overall βhCG immunopostivity was detected in twenty-four (60%) out of the forty cases included in this study. None of PUNLMP cases were positive for βhCG, compared with one out of four (25%) grade 1 tumors, six out of ten (60%) grade 2 and seventeen out of twenty-three (73.9%) of grade 3, a statistically significant positive correlation between βhCG expression and high grade tumors (grade 3), and a negative correlation with PUNLMP were detected. βhCG immuno-postivity was observed in all cases in which multinucleated tumor giant cells (syncytiotrophoplastic-like giant cells) were detected, however no statistically significant correlation was found. βhCG immuno-postivity was detected in five (83.3%) out of six tumors showing squamoid differentiation, in comparison with nineteen (55.9%) out of thirty-four tumors without squamoid differentiation, however also no statistically significant correlation was found.
βhCG expression was found in eight (40%) out of twenty superficial tumors and in sixteen (80%) out of the twenty invasive TCC. None of the three pTa tumors were positive for βhCG, eight (47.1%) out of the seventeen pT1 tumors showed positive reactivity, while βhCG immuno-postivity was observed in sixteen (80%) out of the twenty pT2-4 tumors. A strong statistically significant correlation was found between tumor stage and βhCG expression. Nine (90%) out of the ten cases with associated metastases were positive for βhCG expression, while fifteen (50%) out of thirty cases with no metastases were positive. A statistically significant correlation between βhCG expression and tumors associated with metastases was found.