RESUMEN
The present work aimed to investigate the cellular and immunochemical pattern of T cells population in biopsy material from chronic schistosomiasis haematobium Egyptian patients complicated with bladder cancer. Digital real-time quantitative photocytometry was applied to auto-analyze 29 stained tissue sections from cases and 17 controls using STAT4, GATA3, FOXP3, and CD8 markers specific for Th1, Th2, T regulatory, and T cytotoxic cells, respectively. Area percentage showed significant high level of GATA, followed by FOXP3 and low level of both STAT and CD8 was reported. Tissue samples from five healthy bladder tissues showed significant lower optical density (OD) values. Tissue samples from 12 non-bilharzial bladder cancers showed variable OD values, reflecting wide disparity in the control group.Our results hypothesized an exclusive pattern of T population in long standing complicated schistosomiasis haematobium. Our cases were poorly controlled by unbalanced Th1/Th2 in which Th2 was dominated. FOXP3 increased significantly, however, failed to downregulate Th2, instead, the relation between Th1 and T cytotoxic was forcibly limited by the high level of FOXP3, resulting in loss of their power in defending the host against both parasite and carcinogenic changes. These results provide more clarification for the immune evasion process played by the parasite and tumor cells under the supervision of T regulatory cells. Additionally a critical role of FOXP3 is suggested in manipulating STAT4 and CD8 in favor of malignant transformation in this life-threatening parasite.
Asunto(s)
Linfocitos T Reguladores/patología , Microambiente Tumoral/fisiología , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Femenino , Factores de Transcripción Forkhead , Factor de Transcripción GATA3/metabolismo , Humanos , Recuento de Linfocitos/métodos , Masculino , Persona de Mediana Edad , Factor de Transcripción STAT4/metabolismo , Esquistosomiasis Urinaria/metabolismo , Esquistosomiasis Urinaria/patología , Linfocitos T Reguladores/metabolismo , Células TH1/metabolismo , Células TH1/patología , Células Th2/metabolismo , Células Th2/patología , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
BACKGROUND: Exploration of genetic changes during active Schistosoma infection is important for anticipation and prevention of chronic sequelae. This study aimed to explore the genomic instability in chromosomal and cellular kinetics in Egyptians suffering from uncomplicated active schistosomiasis haematobium infection in addition to chronic schistosomiasis haematobium cases complicated by bilharzial-associated bladder cancer (BAC). RESULTS: This study was conducted on 46 schistosomiasis haemotobium cases, 22 were active (Viable S. haematobium eggs in urine samples as detected by microscopy) and 24 were chronic complicated with bladder cancer. Three cytogenetic techniques were applied; the first was quantitative nuclear-morphocytometry by means of which the Feulgen-stained nuclei were analyzed for parameters including shape, size, integrated optical-density and nuclear area. The second was Fluorescent In-Situ Hybridization (FISH) for specific p53gene-locus of chromosome 17 and the third technique was karyotyping. Concerning chronic complicated cases, the mean ± SD of DNA-content in urinary bladder tissue sections was 3.18 ± 0.65. Five samples (20.83%) of bladder tissue sections of chronic complicated cases showed diploid nuclei, 6 urinary bladder tissue samples (25%) were tetraploid, while 13 bladder samples (54.16%) were aneuploid. Epithelial cells of urine samples demonstrated aneuploidy (mean ± SD = 3.74 ± 0.36).Nuclear contents showed high proliferative DNA index in all urinary epithelial cells. In the acute uncomplicated group, nuclear-DNA of urinary epithelial cells was found diploid with mean nuclear-DNA content of 2.2 ± 0.16SD. Half of these diploid smears had a high proliferation index. The difference between nuclear DNA-contents in acute and chronic cases was significant (P = 0.0001). FISH technique for specific p53gene-locus and karyotyping were done on urinary bladder tissue specimens and peripheral blood monocytes of 8 chronic cases respectively. Three samples (37.5%) with invasive BAC had a deletion of the p53 gene. Karyotyping showed three cases out of the 8 chronic schistosomiasis haematobium patients with chromosomal fragmentations. CONCLUSIONS: DNA morphometry was valuable in detection of gross genetic changes in urothelial tissues. It is an important prognostic factor in established schistosomiasis haematobium induced bladder malignancy. It has the great advantage of being applicable on urine cells making it suitable for the prediction of a tendency towards genetic instability in active schistosomiasis haematobium patients.