OBJECTIVE: The human MAGE 3 gene encodes tumor specific antigens that are recognized by autologue cytotoxic T lymphocytes (CTL). The MAGE 3 gene is expressed not only in melanoma but in the other malignant tumors as well. There is, however, little information on the expression of the gene in uterine cervical carcinomas. The author thus studied the expression of the MAGE 3 gene products in uterine cervical carcinoma and discuss the possibility of specific immunologic diagnosis using MAGE 3 gene products. METHODS: The expression of MAGE 3 gene product in 17 normal tissues of the cervix, 32 cervical intraepithelial neoplasia (8 CIN I, 10 CIN II, 14 CIS), and 43 invasive cervical carcinomas was studied by immunohistochemistry using anti-MAGE 3 mAb 57B in paraffin sections RESULTS: No expression of MAGE 3 gene product was detected in normal cervical tissues and in cervical intraepithelial neoplasias. The expression of MAGE 3 gene product was detected in 30.2% (13/43) of invasive cervical carcinomas. The MAGE 3 gene product was stained as a cytoplasmic protein in cancer cells. No statistically significant differences were observed between MAGE 3 gene product expression status and clinicopathologic parameters. CONCLUSIONS: The MAGE 3 gene products was expressed in invasive cervical carcinoma tissues.
Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Cytoplasm ; Female ; Humans ; Immunohistochemistry ; Immunologic Tests ; Melanoma ; Paraffin ; T-Lymphocytes, Cytotoxic

OBJECTIVE: To explore the role of γδT cells against bladder cancer and to detect the expression of stress proteins MICA/B recognized by γδT cells in bladder cancer. METHODS: γδT cells from peripheral blood drawn from 6 bladder cancer patients with pamidronate stimulating were expanded. Flow cytometry was used to detect the purity and expansion folds of γδT cells, and the expression of CD107a on γδT cells after PMA/ionomycin stimulated. The cytotoxicity assay was carried out to test the cytotoxicity of γδT cells against human bladder cancer cell lines. The expression of MICA/B on bladder cancer cell lines and in bladder cancer tissues were detected through flow cytometry and immunohistochemistry respectively. RESULTS: γδT cells from peripheral blood drawn from 6 bladder cancer patients were successfully expanded. The purity was 75%-94% and the expansion folds were 109-371 times. After being stimulated by PMA/ionomycin, the proportion of CD107a+ γδT cells increased significantly, reaching 40%-82%. γδT cells from the 6 bladder cancer patients showed obvious cytotoxic effects on 3 human bladder cancer cell lines which was enhanced as the effector: the target ratio increased. MICA/B were detected both in 3 bladder cancer cell lines and in 26 bladder cancer tissues. The staining score of MICA/B in invasive bladder cancer was slightly higher than that in non-invasive bladder cancer, and in advanced bladder cancer was higher than that in low grade bladder cancer, but the statistical analysis showed that the staining score of MICA/B was no significant correlation between the tissue and the tumor stages and grades. CONCLUSION γδT cells from the peripheral blood of the bladder cancer patients could be successfully expanded in vitro, and showed significant anti-bladder cancer effect. MICA/B were detected both in bladder cancer cell lines and in bladder cancer tissues. The statistical analysis showed that there was no significant correlation between the staining scores of MICA/B in the tissue and the tumor stages and grades.
Cell Line, Tumor ; Flow Cytometry ; Humans ; Intraepithelial Lymphocytes ; Urinary Bladder Neoplasms

OBJECTIVE: Impaired local cellular immunity contributes to persistent human papillomavirus (HPV) infection and development of cervical intraepithelial neoplasia (CIN). Programmed death-1 (PD-1) and its ligands PD-ligand-1 (L1) and PD-L2 are negative regulators of T cell activity in various cancers, but few studies exist. The aim of this study was to determine the clinicopathologic and immunologic parameters (PD-1, PD-L1, and PD-L2) related to the persistence/recurrence of CIN after conization. METHODS: Medical records of 652 patients diagnosed with CIN and underwent conization were reviewed. The associations between clinicopathologic parameters (e.g., age, parity, initial HPV load, etc.) and persistence/recurrence of CIN were analyzed. Expression of PD-1, PD-L1, and PD-L2 was assessed on 100 conization specimens by immunohistochemistry (IHC) in women matched for propensity-score (50 with persistence/recurrence and 50 without). RESULTS: Initial HPV load (>1,000 relative light unit) and positive margin were shown to be significantly associated with CIN persistence/recurrence (p=0.012 and p < 0.001, respectively). Multivariate analysis showed that margin status was an independent predictor of persistence/recurrence (hazard ratio=8.86; 95% confidence interval=1.67–16.81; p < 0.001). On IHC analysis, none of the patients expressed PD-L1. PD-1+ T cells were observed in 25 of 100 patients. Also, PD-1+ T cells were significantly correlated with increasing grade of CIN (p=0.031). In addition, patients with persistence/recurrence had increased expression of PD-1 compared with those without (36% vs. 14%, respectively; p=0.020). Although PD-L2 expression did not differ between 2 groups, it was significantly higher in patients with high-grade CIN compared to low-grade (34.7% vs. 12%, respectively; p=0.041). CONCLUSION: Positive surgical margin and expression of PD-1+ T cells were associated with CIN persistence/recurrence after conization.
Cervical Intraepithelial Neoplasia* ; Conization* ; Female ; Humans ; Immunity, Cellular ; Immunohistochemistry ; Ligands ; Medical Records ; Multivariate Analysis ; Papillomaviridae ; Parity ; Recurrence* ; T-Lymphocytes

OBJECTIVE: Uterine cervical cancer is the most common malignant tumor in Korean women. Human papillomaviruses are associated in 85-90% of the cases. However, other cofactors are considered to be important in carcinogenesis. There is an evidence that the uterine cervix is the site of shedding of the Epstein-Barr viruses(EBV). Furthermore the virus has been detected in cervical intraepithelial neoplasia and invasive carcinoma of the uterine cervix. We studied to evaluate the role of EBV in cervical carcinogenesis. METHODS: Non-neoplastic cervices(12), carcinoma in situ(32), microinvasive squamous cell carcinomas(9), invasive squamous cell carcinomas(37) and adenocarcinomas and adenosquamous carcinomas(14) were studied for EBV infection. PCR and in situ PCR for EBNA-1 were done and subtyping was done using PCR for EBNA 3C. RESULTS: In non-neoplastic cervix, EBV was detected in 16.7% by PCR and found in normal epithelial cells and lymphocytes in in situ PCR. By PCR technique, EBV was detected in 65.6% of CIS, 66.3% and 51.4% of microinvasive and invasive squamous cell carcinomas, 57.1% of adenocarcinomas and adenosquamous carcinomas. EBV subtyping was done in EBV positive cases by PCR and all showed type 1. CONCLUSION: EBV was detected in higher frequency in cervical cancer than in non-neoplastic cervix. However the frequency was not correlated to the invasion depth and histologic types of cervical carcinomas. EBV was detected in tumor cells as well as normal epithelial cells and lymphocytes also. It was suggested that EBV may play a role in cervical cancers but the mechanism in carcinogenesis remains to be solved.
Adenocarcinoma ; Carcinogenesis ; Carcinoma, Adenosquamous ; Carcinoma, Squamous Cell ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Epithelial Cells ; Epstein-Barr Virus Infections ; Female ; Herpesvirus 4, Human* ; Humans ; Lymphocytes ; Polymerase Chain Reaction* ; Prevalence* ; Uterine Cervical Neoplasms*