Prognostic significance of inflammation-based prognostic scoring in patients with upper urinary tract urothelial carcinoma

ABSTRACT Objectives: To investigate whether Glasgow Prognostic Score has prognostic significance in patients with upper urinary urothelial carcinoma. Patients and methods: We retrospectively reviewed the clinical records of 74 patients with upper urinary urothelial carcinoma. We set the cut-off value for C-reactive protein as 1.0mg/dL, and 3.5mg/dL for albumin as Glasgow Prognostic Score. Their blood data including albumin and C-reactive protein for Glasgow Prognostic Score and cytokeratin 19 fragment 21-1 as a tumor marker were measured before starting treatment. The patients were stratified into three groups with Glasgow Prognostic Score: The Group-1, albumin ≥3.5g/dL and C-reactive protein < 1.0mg/dL; Group-2, albumin < 3.5g/dL or C-reactive protein ≥1.0mg/dL; Group-3, albumin < 3.5g/dL and C-reactive protein ≥1.0mg/dL. Results: The median follow-up for all patients was 26.9 months (range: 10.9-91.1 months), during which 37 (50%) patients died. There was a significant difference in the estimated survival rate among the 3 groups stratified by Glasgow Prognostic Score. The estimated survival rate in the Group-1 was significantly higher than those in Groups 2 and 3. In the univariate analysis C-reactive protein, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were significant predictors of overall survival. On the multivariate analysis, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were independently associated with shorter overall survival. Conclusion: Our review suggests Glasgow Prognostic Score may play as a prognostic predictor for upper urinary urothelial carcinoma.

Detection of Circulating Tumor Cells in Breast Cancer Patients Using Cytokeratin-19 Real-Time RT-PCR

PURPOSE: The roles of circulating tumor cells (CTCs) as predictive and prognostic factors, as well as key mediators in the metastatic cascade, have been investigated. This study aimed to validate a method to quantify CTCs in peripheral blood using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay for cytokeratin (CK)-19 and to evaluate the utility of this assay in detecting CTCs in breast cancer patients. MATERIALS AND METHODS: Real-time monitoring PCR of fluorescently labeled specific hybridization probes for CK-19 mRNA was established. Peripheral blood samples from 30 healthy donors, 69 patients with early breast cancer, 47 patients with locally advanced breast cancer, and 126 patients with metastatic breast cancer were prospectively obtained and analyzed for CTC detection. RESULTS: CK-19 mRNA was not detectable in healthy subjects using the real-time RT-PCR method. The detection rates of CK-19 mRNA in breast cancer patients were 47.8% for early breast cancer (33/69), 46.8% for locally advanced breast cancer (22/47), and 61.1% for metastatic breast cancer (77/129). The detection rate of CK-19-positive CTCs in metastatic disease was slightly higher than early or locally advanced breast cancer; however, the detection rate according to disease burden was not statistically different (p=0.097). The detection rate was higher in patients with pleural metastasis (p=0.045). CTC detection was associated with poor survival (p=0.014). CONCLUSION: A highly specific and sensitive CK-19 mRNA-based method to detect CTCs in peripheral blood in breast cancer patients can be used in further prospective studies to evaluate the predictive and prognostic importance of CTCs.

Diagnostic values of gene expression of cytokeratin - 19 mrna and mammaglobin mrna in breast cancer patients using real-time polymerase chain reaction

Breast cancer is the most frequent cancer in women. It constitutes almost 20% of all malignancies in women. Currently it affects approximately 6% of the female population. Even before clinical detection of a primary tumour, cancer cells can invade the adjacent structures from where they travel through lymphatic and blood vessels as circulating tumour cells [CTCs]. CTCs colonize distant organ sites as disseminated tumour cells [DTCs] and eventually form microscopic deposits [micrometastasis < 2 mm in diameter], which may remain dormant, but then ultimately lead to an overt metastatic disease. Cytokeratins [CKs] have become the most widely accepted protein markers for the detection of epithelial tumour cells in mesenchymal tissues, BM, blood and lymph nodes. Based on its breast cancer-association and somewhat unique breast-specific pattern of expression, mammaglobin was believed to be an excellent candidate for a novel and clinically useful breast tumor marker, especially in detecting micrometastasis. This study was performed on one hundred female Individuals. They classified into: Group I: 20 apparently healthy females as control group. Group II: 20 females with stage I breast cancer . Group HI: 20 females with stage II breast cancer. Group IV: 20 females with stage III breast cancer. Group V: 20 females with stage IV breast cancer. The following specific investigations were done for all the studied persons:-Cancer Antigen 15-3 [CA15-3] and Carcinoembryonic Antigen [CEA] using chemilmnmescent immunometric assay [IMMULITE 1000 Analyzer]. Cytokeratin-19 mRNA [CK-19] mRNA and mammaglobin mRNA by Real-time polymerase chain reaction [RT-PCR]. In group I [control group]: All the 20 healthy control females had low expression values for CK-19 and Mammaglobin. In group 2 [stage I breast cancer]: 35% of patients had over expression values for CK-19 and 20% had over expression values for Mammaglobin. In group 3[stage II breast cancer]: 47.4% of patients had over expression values for CK-19 and 47.4% had over expression values for Mammaglobin. In group 4 [stage III breast cancer] 68.4% of patients had over expression values for CK-19 and 73.7% had over expression values for Mammaglobin. In group 5 [stage IV breast cancer]: 95% of patients had over expression values for CK-19 and 95% had over expression values for Mammaglobin. Our findings support that all patients with breast cancer should be evaluated by CK-19 and Mammaglobin as a regular laboratory assessment beside the routine tumour markers specially in early stages of breast cancer to detect CTCs at the time of diagnosis

Reverse transcriptase polymerase chain reaction study to evaluate dissemination of cancer cells into circulation after incision biopsy in oral squamous cell carcinoma.

BACKGROUND: Tissue manipulation by incisions, radiotherapy, and palpation may lead to dissemination of cancer cells into circulation. Circulating cancer cells in blood play a central role in metastatic process. Their numbers can be very small and for their detection,reverse transcriptase polymerase chain reaction (RT-PCR) has been successfully used in this study. MATERIALS AND METHODS: To examine whether cancer cell dissemination results from incision biopsy, we tried to detect oral squamous cell carcinoma (OSCC) cells in the peripheral blood sample before and after incision biopsy by CK19 RT-PCR. The study group consisted of 25 OSCC patients and the control group consisted of five patients with oral submucos fibrosis and five with leukoplakia. Five ml of blood collected before and twice (15 and 30 min) after incision were used for CK19 RT-PCR. RESULTS: Four (16%) of 25 cases of OSCC were positive for CK19 transcripts in their peripheral blood drained 15 min after incision. CK19 transcripts were not detected in the control group. CONCLUSION: Surgical invasion, in the form of incisional biopsy, causes dissemination of cancer cells into circulation, resulting in increased risk of metastasis.