The role of TGF-beta-1 protein and TGF-beta-R-1 receptor in immune escape mechanism in bladder cancer.
BACKGROUND
Tumor cells have numerous immune surveillance escape mechanisms as well as means of resistance to apoptosis. This study tried to clarify one of these mechanisms in bladder cancer with the hope of being able to develop targeted therapy that will sensitize the tumor cells to immune-mediated apoptosis.


METHODS
In this study, electron microscopic examination and expression of TGF-beta-1 protein and TGF-beta-R-1 receptor using immunoelectronmicroscopic and immunocytochemical techniques were investigated in urine and peripheral blood mononuclear cells (PBMNCs). Samples were obtained from 5 healthy controls (Group 1) and 60 study patients who were classified according to the cytopathologic examination of their urine into 2 main subgroups: chronic cystitis (bilharzial and nonbilharzial, Group 2, n = 15) and bladder cancer (transitional cell carcinoma and squamous cell carcinoma, Group 3, n = 45).


RESULTS
Examination of PBMNCs by immunoelectronmicroscopic and immunocytochemical techniques showed a significant increase in the percentage of positive cases expressing both TGF-beta-1 protein and TGF-beta-R-1 receptors in bladder cancer in comparison with the control (P < .01 and P < .05, respectively) and with chronic cystitis (P < .05). By electron microscopic examination, 42 out of 45 bladder cancer cases (93.3%) revealed remarkable apoptotic changes represented by cell shrinkage, surface blebs, nuclear chromatin condensation, and vacuolated cytoplasm. Urine examination by immunoelectronmicroscopic and immunocytochemical techniques revealed a statistically significant decrease in the percentage of positive cases expressing TGF-beta-R1 receptor in bladder cancer in comparison with either chronic cystitis cases or controls (P < .01), while TGF-beta-1 protein was significantly increased (P < .01). By electron microscopic examination, exfoliated necrotic malignant epithelial (urothelial) cells and many inflammatory cells were detected.


CONCLUSIONS
This work helps researchers and clinicians to better understand one of the escape mechanisms in bladder cancer that may facilitate the reverse of tumor escape from the immune system. It also draws attention to TGF-beta-1 protein and TGF-beta-R1 receptor; TGF-beta-1 protein can be used as an attractive target for anticancer therapy, and the absence of TGF-beta-R1 can be considered a marker for malignant transformation of urothelial cells in bladder cancer.
Helmy
Amira
A
Theodor Bilharz Research Institute, Electron Microscopy Department, Cairo, Egypt. amira7121956@yahoo.com
Hammam
Olfat Ali
OA
El Lithy
Tarek Ramzy
TR
El Deen Wishahi
Mohamed Mohi
MM
D000368:Aged; D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000276:immunology / Q000473:pathology / Q000652:urine; D016022:Case-Control Studies; D003556:Cystitis / Q000175:diagnosis* / Q000276:immunology / Q000652:urine; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000276:immunology*; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000276:immunology*; D016482:Urinalysis; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000473:pathology / Q000652:urine*; D014556:Urine / Q000166:cytology*
D015415:Biomarkers; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1