| Bladder cancer is one of the most common tumor of urinary system in our country. In recent years the trend of its incidence has increased. Statistics show that male bladder cancer mortality rate was 4.2/100000, female bladder cancer mortality rate was 1.1/100000.About 75% of bladder cancer at the beginning is superficial bladder cancer,without treatment after surgical resection, in 1 to 3 years the relapse rate of about 50% to 70% and 10% to 20% may progress to deep infiltration, survival rate decreased significantly.Resection of cancer tissue in the bladder later cytotoxic chemotherapy drugs can delay the disease process reduce the relapse rate, but different drugs, a great deal of difference in efficacy,Reported in the literature, the use of mitomycin bladder 1 to 3 years the relapse rate can be reduced to 30%～40%,joint THP and BCG perfusion 1 to 3year recurrence rate was 20%～30%.If you can accurately assess the risk of tumor recurrence, recurrent cancer was found early and timely intervention on the treatment,for bladder cancer treatment and prognosis of patients has important clinical significance.At present, the diagnosis of bladder cancer and postoperative follow-up mainly through urine cytology, imaging and cystoscopy.These methods have difficulty in the diagnosis of carcinoma in situ, micro-flat low-grade tumors and the malignant tumors and so on.In recent years, with the nature of bladder cancer in-depth study of immunology and cell and molecular biology technology, in patients with bladder cancer in urine DNA level, mRNA level and the level of protein and its decomposition products are always new tumor markers were found, and some have been successfully applied to monitoring and diagnosis of clinical relapse.In the United States, FDA has approved the testing method are as follows:1.Bladder tumor antigen (BTA): BTA is the process of bladder tumor growth into the bladder to release the complex,Detection methods BTA, BTAstat, BTA Trak, BTA's misdiagnosis and missed diagnosis rates are high,BTA stat and BTA Trak was developed on the basis of BTA, and its overall sensitivity of 51% ~ 76% and 62% ~ 77%, the overall specificity was 70% ~ 86% and 48% ~ 70%.They are of the view that the diagnosis of bladder cancer in the application of the value are small,In the course of postoperative follow-up of dynamic observation of the titer in urine to predict the recurrence have a certain value.2. Immunodeficiency - Cell Test (Immunocyt): Immunocyt in the cell level through immunochemistry monoclonal antibody chromosome fluorescence detection, using the three kinds of monoclonal antibodies for bladder cancer,have a relative specificity to detect that antigen showed in bladder cancer cells.Most of this antigen in bladder cancer cell surface expression, and not expression in the normal urothelial.Study shows that, Immunocyt detection sensitivity of the diagnosis of bladder cancer was 84% ~ 90%, specificity is 69% ~ 79%.3.Urinary nuclear matrix protein 22 (NMP22): NMP is the nucleus of a network structure of the protein, its function primarily involved in DNA replication, RNA synthesis and the regulation of gene expression and so on.In different tumors, the specificity of tumor-associated nuclear matrix proteins have been discovered. The study found that patients with bladder cancer NMP22 protein expression was significantly increased, due to the loss and apoptosis in cancer cells so that a large number of the release of NMP22 in urine.Urine NMP22 detected by semi-quantitative method, the normal value for 10U/ml, the sensitivity of diagnosis of bladder cancer is 47% ~ 100% and specificity of 60% ~ 90%.The above-mentioned methods and compared with urine cytology have a high diagnostic sensitivity (16% ~ 90%, most in the 50% upper and lower), However, susceptible to hematuria, urinary tract infection, chemotherapy appeared false positive.Tumor cell genome of non-equilibrium change is the root causes of tumor occurrence and development,Cytogenetics demonstrated in chromosome number or structure for the anomaly, at the molecular level can be reflected in the amplified DNA fragment, deletion, methylation, and base changes.The study of tumor cells on chromosome structure and structural changes, you can type in the nuclear level to further assess the biological behavior of tumor cells,There are significant clinical value.Fluorescence in situ hybridization (FISH) with the basic principles are known biotin or digoxigenin labeled fluorescent substances, single-stranded nucleic acid as a probe, in accordance with the principle of complementary base pairs with the seized materials to be unknown single-stranded nucleic acid specific to the combination of detection of the formation may be double-stranded nucleic acid hybridization. In fluorescence microscope combined with the probe specific gene in chromosome positioning. FISH interphase cells can be found in the number of nuclear chromosomes and structural changes,can be found as early as the pathological changes in the tumor,without the impact of hematuria,infusion chemotherapy,so FISH in bladder cancer in the applied research has been extensive attention in recent years.Sokolova first reported in 2000 the Joint Application of 3,7,17 and chromosome 9p21 probe (UroVysion) diagnosis of bladder cancer with high sensitivity and specificity, the United States FDA in 2001 and 2005, respectively, approved the UroVysion Kit Clinical applications for the recurrence of bladder cancer, early diagnosis and in patients with suspicious symptoms of hematuria screening.Halling also confirmed that FISH technology in all phases of classification and diagnosis of bladder cancer were significantly higher than the sensitivity of urine cytology.Halling also confirmed that FISH technology in all phases of classification and diagnosis of bladder cancer were significantly higher than the sensitivity of urine cytology. Friedrich compared the sensitivity of multicolor FISH, BTA stat, NMP22,that the sensitivity of three similar,but in the specific multi-color FISH was significantly higher than the other two methods.Sarosody found 36 cases of bladder examination and FISH-negative-positive patients, after 16 months follow-up, 15 cases (42%) occurred in bladder cancer; and 68 cases of cystoscopy and urine cytology were negative for the patients, follow-up 19 months, only 13 cases (19%) for bladder cancer development.Yoder compared 250 bladder cancer in urine cytology, FISH, bladder examination results: 81 cases of patients with FISH-positive 60 cases (74.0%) relapse, 169 cases of patients with negative FISH only 22 cases of recurrence (13%).Skacel study the diagnosis of bladder cancer in FISH technology overall sensitivity and specificity were 85% and 97%.Recently, Sarosdy proposed the concept of the expected positive (FISH-positive, cystoscopy or urine cytology-negative patients), FISH-positive patients that relapse and progress of the time was shorter than in FISH-negative.However, the above-mentioned results of the chromosome probe in different combinations there are differences, there is no uniform standard.On risk assessment in the tumor, According to FISH results Bollmann had the superficial bladder cancer into low-risk (9p21 or combined low-frequency degrees of individual cells, chromosomes 3,7,17 four times) and high risk (multiple and different chromosome ploidy),In 11 cases of high-risk group 5 cases recurrence,17 cases of low-risk group, only four cases of recurrence, and occurrence of progress occurred in only four cases of high-risk group.Progress occurs only four cases occurred in high-risk group.Pycha through FISH detected 51 cases of superficial bladder cancer found that 20 cases for 9p21 deletion and / or chromosome 3 of the multi-body, 15 were 7 / 17 chromosomes of the multi-body, the former only three cases of recurrence, which has nine cases of recurrence, and five cases of recurrence after the progress.All these show that the FISH technique based on changes in the different karyotypes predictable risk of tumor recurrence and progress.Also in the FISH technique to guide the way bladder cancer surgery and postoperative chemotherapy also have an advantage.Kipp found bladder before and after chemotherapy were FISH-positive patients, the recurrence risk is negative FISH were 5.3 times; and reperfusion FISH positive clinical progress of the risk is 9.4 times the FISH-negative patients, which prompted the clinical results can be taken in accordance with FISH individualized chemotherapy or surgery to take a more active approach in order to obtain better treatment.we study the relationship between paraffin tissue Karyotype variation and recurrence of superficial bladder cancer in our country. The results show that bladder cancer cells that exist in the number of abnormal chromosomes 7,17, The number of chromosome 7,17abnormalities associated with bladder cancer recurrence, has nothing to do with the recurrence number.Abnormal chromosome 17 in patients with disease-free survival time were shorter than normal,The possibility of recurrence is 2 times of normal.Paraffin specimens can be retrospectively analyzed the relationship between chromosome 7,17 and the recurrence and progress of bladder cancer,However, based on the time fixed, not dynamic response of bladder cancer chromosome changes, and in the process of paraffin-embedded,it is possible to chromosome damage caused by changes in the nucleus.Therefore, based on preliminary studies, we further Collecting urine specimens of patients with bladder cancer,to observed chromosome 7 and 17 Karyotype variability in patients with bladder cancer in our country,and prognosis with conventional pathological parameters of comparison, To determine the relationship between the karyotype abnormalities and biological behavior of bladder cancer, at the same time, assessment the clinical feasibility of FISH technology to monitor the early postoperative recurrence of bladder cancer.Research MethodsFresh morning urine samples taken from our hospital and Drum Tower Hospital from July 2002 to October 2007 follow-up data between the range of superficial bladder cancer patients, male 49 cases, 17 cases of women aged 47~84 year old (average 63.2 years). Up for 3 years to 5 years, 42 cases of tumor recurrence, 24 cases of non-recurrence.Combined with clinical information,Explore the relationship between the rate of chromosome7,17 abnormalities in urinary exfoliated cells and the biological behavior.Research ResultsThe results showed that 7,17 chromosome aneuploidy rates were 48.5% (32/66) and 50.0% (33/66), abnormal expression of both 25.8% (17/66). At G2/3 bladder cancer, the recurrence of tumor on the 17th chromosome aneuploidy rate (64.3%) was significantly higher than non-recurrent tumors (22.2%) (P<0.05), and G1 bladder cancer, the tumor recurrence and no recurrence 7, chromosome 17 aneuploidy was no significant difference (P>0.05). At pTa and pT1 bladder cancer and found no tumor recurrence and chromosomal abnormalities, but in pT1 bladder cancer, the tumor recurrence 7 and 17 simultaneously abnormal chromosome expression (47.8%) was significantly higher than tumor recurrence (12.5%) (P<0.05). In 14 cases of relapse after the progress of bladder cancer, 7 and 17 chromosome aneuploidy rate (78.6%, 92.9%) was significantly higher than the progress of cancer did not (42.9%, 46.4%) (P<0.05). These results suggest that patients with bladder cancer in urine exfoliated cells of chromosome abnormalities contribute to determine the postoperative recurrence and clinical progress.ConclusionsThe results showed that urine exfoliated cells of bladder cancer chromosome variation exists,Changes in chromosome 17 associated with superficial bladder cancer recurrence, but the combined detection of chromosome 7,17 predict bladder cancer recurrence and more efficient progress. Chromosome check in Exfoliated cells in urine can be used as a one of the indicators of postoperative follow-up. According to the characteristics of easy to relapse and early relapse,bladder cancer patients in chromosomal abnormalities can be given in the postoperative follow-up more closely in order to early detection of recurrence, prompt treatment to improve therapeutic effects. |
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