Genomic Instability and the Development of Metastatic Lymph Node Tumors

Background Although recent data suggest that cells with metastatic potential disseminate from the primary breast tumor early in tumor development, the mechanism by which disseminated breast cancer cells proliferate within foreign tissues is not well understood. Here, we examined levels and patterns of allelic imbalance (AI) in metastatic lymph node (LN) tumors to identify molecular signals that promote the survival and growth of disseminated breast tumor cells. Methods DNA from 106 metastatic LN tumors from 25 patients was isolated after laser microdissection of pure tumor cell populations. AI was assessed at 26 chromosomal regions frequently altered in breast cancer. Tumor burden was calculated by dividing the area of the metastatic tumor in the node by the area of the entire LN. Results Metastatic tumor burden ranged from focal to complete replacement of the LN with tumor. Grouping the nodes as <25% tumor, 25–50% tumor, 50–75% tumor, and ≥75% tumor replacement revealed the average frequency of AI ranged from 0.13 (±0.11) in the <25% group to 0.17 (±0.13) in LNs with ≥75% tumor burden. The range of AI in both the <25% and >75% replacement group was 0.00–0.48. Allelic losses at chromosomal regions 1p36.1–36.2, 5q21.1–21.3, 6q15, 10q23.31–23.33, and 17p13.1 were significantly higher in metastatic LNs with >75% compared with <25% tumor burden. Conclusions In metastatic LNs, levels of AI were not associated with tumor burden, suggesting that accumulation of genetic changes is not coincidental with tumor growth; rather the accumulation of specific genetic changes is a prerequisite to the transformation of disseminated breast cells into metastatic LN tumors. Grant support: This work was performed under the auspices of the Clinical Breast Care Project with funding provided by the United States Department of Defense through the Army Medical Research and Materiel Command (MRMC)/Telemedicine and Advanced Technology Research Center (TATRC), Fort Detrick, MD and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD (MDA 905-00-1-0022 to CDS). The opinions expressed herein are solely those of the authors and do not represent the opinions of the Department of Defense.     

Genomic Alterations Associated with Early Stages of Breast Tumor Metastasis

Background  Molecular studies suggest that acquisition of metastatic potential occurs early in the development of breast cancer; mechanisms by which cells disseminate from the primary carcinomas and successfully colonize foreign tissues are, however, largely unknown. Thus, we examined levels and patterns of chromosomal alterations in primary breast tumors from node-negative (n = 114) and node-positive (n = 115) patients to determine whether specific genomic changes are associated with tumor metastasis. Methods  Fifty-two genetic markers representing 26 chromosomal regions commonly altered in breast cancer were examined in laser microdissected tumor samples to assess levels and patterns of allelic imbalance (AI). Real time-PCR (RT-PCR) was performed to determine expression levels of candidate genes. Data was analyzed using exact unconditional and Student’s t-tests with significance values of P < 0.05 and P < 0.002 used for the clinicopathological and genomic analyses, respectively. Results  Overall levels of AI in primary breast tumors from node-negative (20.8%) and node-positive (21.9%) patients did not differ significantly (P = 0.291). When data were examined by chromosomal region, only chromosome 8q24 showed significantly higher levels (P < 0.0005) of AI in node-positive primary tumors (23%) versus node-negative samples (6%). c-MYC showed significantly higher levels of gene expression in primary breast tumors from patients with lymph node metastasis. Conclusions  Higher frequencies of AI at chromosome 8q24 in patients with positive lymph nodes suggest that genetic changes in this region are important to the process of metastasis. Because overexpression of c-MYC has been associated with cellular dissemination as well as development of the premetastatic niche, alterations of the 8q24 region, including c-MYC, may be key determinants in the development of lymph node metastasis. Contact for reprints: Ms. Kerri Cronin, Clinical Breast Care Project, Walter Reed Army Medical Center, 6900 Georgia Avenue, NW Washington, DC 20307, Tel.: +1 (202) 782-0002, E-mail: kerri.cronin@amedd.army.mil.     

Correlation of Levels and Patterns of Genomic Instability With Histological Grading of DCIS

BACKGROUND: Histological grading of ductal carcinoma-in-situ (DCIS) lesions separates DCIS into three subgroups (well-, moderately, or poorly differentiated). It is unclear, however, whether breast disease progresses along a histological continuum or whether each grade represents a separate disease. In this study, levels and patterns of allelic imbalance (AI) were examined in DCIS lesions to develop molecular models that can distinguish pathological classifications of DCIS. METHODS: Laser microdissected DNA samples were collected from DCIS lesions characterized by a single pathologist including well- (n = 18), moderately (n = 35), and poorly differentiated (n = 47) lesions. A panel of 52 microsatellite markers representing 26 chromosomal regions commonly altered in breast cancer was used to assess patterns of AI. RESULTS: The overall frequency of AI increased significantly (P < .001) with increasing grade (well differentiated, 12%; moderately differentiated, 17%; poorly differentiated, 26%). Levels of AI were not significantly different between well- and moderately differentiated grades of disease but were significantly higher (P < .0001) in poorly differentiated compared with well- or moderately differentiated disease. No statistically significant differences in patterns of AI were detected between well- and moderately differentiated disease; however, AI occurred significantly more frequently (P < .05) in high-grade lesions at chromosomes 6q25-q27, 8q24, 9p21, 13q14, and 17p13.1, and significantly more frequently in low-grade lesions at chromosome 16q22.3-q24.3. CONCLUSIONS: The inability to discriminate DCIS at the genetic level suggests that grades 1 and 2 DCIS may represent a single, non-high-grade form of DCIS, whereas poorly differentiated DCIS seems to be a genetically more advanced disease that may represent a discrete disease entity, characterized by a unique spectrum of genetic alterations.     

Implication of the BRCA2 and Putative “BRCA3” Genes in Dukes’ Stage C, Replication Error–Negative Colon Cancer

Background Although BRCA genes have been implicated in certain tumors, particularly breast tumors, their role in colon tumorigenesis has not been fully explored. We aimed to investigate the association of the BRCA2 and putative “BRCA3” genes in a homogeneous series of right-sided colon cancer specimens. Methods Twenty-three Dukes’ stage C, replication error–negative carcinomas were selected from patients with right-sided colon cancer. After histological examination and microdissection, DNA was extracted from normal colon and carcinoma from each patient. Five microsatellite markers spanning the region of BRCA2 and BRCA3 on chromosome 13 (D13S218, D13S219, D13S165, D13S156, and D13S160) and two markers intragenic to BRCA2 and BRCA3 (D13S171 and D13S1308, respectively) were used. Polymerase chain reaction products were analyzed by using a fluorescent allele imbalance assay. Results Markers demonstrating the highest allelic imbalance were D13S1308 (53%), D13S171 (33%), and D13S160 (37%). Conclusions The intragenic markers D13S1308 (BRCA3) and D13S171 (BRCA2) on chromosome 13 demonstrated a high frequency of allelic imbalance in primary colon carcinoma. This suggests an involvement of BRCA2 and putative BRCA3 in colon tumorigenesis in right-sided, replication error–negative, Dukes’ stage C cancers. Further studies are needed to confirm the precise role of these genes, and any prognostic significance, in colon cancer. This article was previously published in abstract form (Sivarajasingham NS, Cawkwell L, Tilsed JV, Greenman J, Monson JRT. Implication of BRCA genes in colon tumorigenesis. Ann Surg Oncol 2004;11:S114).     

The Genomic Heritage of Lymph Node Metastases: Implications for Clinical Management of Patients with Breast Cancer

Background Metastatic breast cancer is an aggressive disease associated with recurrence and decreased survival. To improve outcomes and develop more effective treatment strategies for patients with breast cancer, it is important to understand the molecular mechanisms underlying metastasis. Methods We used allelic imbalance (AI) to determine the molecular heritage of primary breast tumors and corresponding metastases to the axillary lymph nodes. Paraffin-embedded samples from primary breast tumors and matched metastases (n = 146) were collected from 26 patients with node-positive breast cancer involving multiple axillary nodes. Hierarchical clustering was used to assess overall differences in the patterns of AI, and phylogenetic analysis inferred the molecular heritage of axillary lymph node metastases. Results Overall frequencies of AI were significantly higher (P < 0.01) in primary breast tumors (23%) than in lymph node metastases (15%), and there was a high degree of discordance in patterns of AI between primary breast carcinomas and the metastases. Metastatic tumors in the axillary nodes showed different patterns of chromosomal changes, suggesting that multiple molecular mechanisms may govern the process of metastasis in individual patients. Some metastases progressed with few genomic alterations, while others harbored many chromosomal alterations present in the primary tumor. Conclusions The extent of genomic heterogeneity in axillary lymph node metastases differs markedly among individual patients. Genomic diversity may be associated with response to adjuvant therapy, recurrence, and survival, and thus may be important in improving clinical management of breast cancer patients.     

Localization of the Sentinel Node of the Upper Outer Breast Quadrant in the Axillary Quadrants

Background

Sentinel node (SN) biopsy is associated with much less morbidity than axillary dissection. In patients with early breast cancer, lymphatic mapping and SN biopsy accurately stage the axillary nodes. Both currently available lymphatic mapping agents, radiocolloid and blue dye, have some limitations that may make perioperative or preoperative SN identification difficult. In such cases, exact knowledge of the topography of the axilla and the most probable location of the SN may be crucial.

Methods

In 12 fresh female cadavers with no history of breast carcinoma, injections of patent blue dye were used to visualize the SNs in the axillary quadrants and their lymphatic collectors from the upper outer quadrant of the breast, which is the most common location of breast cancer. The axilla was divided into quadrants with regard to the intersection of the thoracoepigastric vein and the third intercostobrachial nerve.

Results

All SNs were located within a circle of 2-cm radius of this intersection in the fatty tissue at the clavipectoral fascia. In most cases, the SN was located in the fatty tissue near the clavipectoral fascia in the lower ventral quadrant of the axilla (n = 14, 58%). In seven cases (29%), the SN was located in the upper ventral quadrant, in two cases (8%) in the upper dorsal quadrant, and in one case in the lower dorsal quadrant.

Conclusions

The results of this anatomical study may facilitate SN biopsy in patients with breast cancer.     

Timing of Critical Genetic Changes in Human Breast Disease

Background Breast cancer development has been characterized as a nonobligatory sequence of histological changes from normal epithelium through invasive malignancy. Although genetic alterations are thought to accumulate stochastically during tumorigenesis, little is known about the timing of critical mutations. This study examined allelic imbalance (AI) in tissue samples representing a continuum of breast cancer development to examine the evolution of genomic instability. Methods Laser-microdissected DNA samples were collected from histologically normal breast specimens (n = 25), atypical ductal hyperplasia (ADH, n = 16), ductal carcinoma-in-situ (DCIS, n = 37), and stage I to III invasive carcinomas (n = 72). Fifty-two microsatellite markers representing 26 chromosomal regions commonly deleted in breast cancer were used to assess patterns of AI. Results AI frequencies were <5% in histologically normal and ADH specimens, 20% in DCIS lesions, and approximately 25% in invasive tumors. Mann-Whitney tests showed (1) that levels of AI in ADH samples did not differ significantly from those in histologically normal tissues and (2) that AI frequencies in DCIS lesions were not significantly different from those in invasive carcinomas. ADH and DCIS samples, however, differed significantly (P < .0001). Conclusions DCIS lesions contain levels of genomic instability that are characteristic of advanced invasive tumors, and this suggests that the biology of a developing carcinoma may already be predetermined by the in situ stage. Observations that levels of AI in ADH lesions are similar to those in disease-free tissues provide a genomic rationale for why prevention strategies at the ADH level are successful and why cases with ADH involving surgical margins do not require further resection.     

Surgical Resection of the Primary Tumor is Associated with Increased Long-Term Survival in Patients with Stage IV Breast Cancer after Controlling for Site of Metastasis

Background The benefit of surgical resection in patients presenting with metastatic breast cancer is not established. We hypothesized that surgical excision of primary tumors in patients with stage IV breast cancer would be associated with increased survival. Methods Chart review identified 409 patients with stage IV breast cancer treated from 1996 to 2005; 187 received surgical excision of their primary tumor and 222 did not. One hundred and two patients had bone-only metastases, 281 had metastases to other organs ± bone, and 26 had no metastases recorded. Patient characteristics were compared between groups using the chi-squared test. Cox regression models were used to calculate adjusted hazard ratios (aHR). The log-rank test compared the differences in survival between patients who did or did not undergo surgical resection. Results Mean age at diagnosis of all 409 patients was 57.8 ± 15.0 years. After controlling for age, comorbidity, tumor grade, histology, and sites of metastasis, patients who underwent surgical resection had longer median survival when compared with patients who did not undergo surgical resection (31.9 vs. 15.4 months, p < 0.0001; aHR 0.53 [95% CI 0.42-0.67]). Conclusions Surgical excision of the primary breast tumor was associated with significantly longer survival in this cohort of stage IV breast cancer patients, even after controlling for other factors associated with survival. Randomized clinical trials are needed to validate these findings.     

microRNA与乳腺癌浸润转移关系的研究进展

目的总结microRNA（miRNA）与乳腺癌浸润、转移关系的研究进展。方法检索并筛选近年来国内外发表的有关miRNA与乳腺癌浸润、转移关系的文献并对其进行综述。结果许多miRNA在乳腺癌发生、发展与浸润、转移过程中都起着关键作用,按其作用可分为促癌miRNA（miR-21、miR-10b等）和抑癌miRNA（miR-31、let-7等）两类。结论miRNA调控乳腺癌浸润及转移的具体过程还需要更多、更详细的实验研究。     

多重置换扩增结合激光捕获显微切割技术在胃癌基因组学研究中的应用

目的探讨多重置换扩增（MDA）与激光捕获显微切割（LCM）技术相结合，并应用到胃癌细胞杂合性丢失（LOH）分析等研究的可行性。方法利用LCM技术从胃癌组织冰冻切片中分别获取正常胃黏膜细胞和胃癌细胞，提取基因组DNA后，进行全基因组多重置换扩增。进而，将MDA产物用于聚合酶链反应（PCR）扩增ACE2、TP53和ACTB基因片段，以及微卫星位点的LOH分析。结果位于不同染色体的3个基因片段均得到较好的扩增，而且MDA产物的扩增效率明显高于未经MDA的基因组DNA。另外，MDA产物的LOH分析结果与未经MDA的基因组DNA结果一致。结论MDA与LCM技术相结合，是一种可行的全基因组扩增技术路线，可用于后续的基因组学研究。     

Multifaceted Roles of Integrins in Breast Cancer Metastasis

Malignant breast cancer can be a debilitating disease due to metastasis to tissues such as brain or bone. The metastatic process involves the invasion of tumor cells into the adjacent tissue, followed by systemic dissemination and colonization of secondary organs. These processes require interactions between tumor cells and a changing microenvironment, which drive cell proliferation, migration, invasion and colonization, as well as promoting cell survival. The integrin family of cell adhesion receptors has been shown to play a critical role in all of these processes, consistent with their extracellular matrix binding properties. Experiments in cultured epithelial cells and in vivo models have demonstrated that integrins can promote various stages of metastasis by modulating the effects of growth factor receptors, extracellular proteases and chemotactic molecules. Integrins may therefore play a pivotal role in multiple mechanisms of metastasis. As a result, they represent promising targets for effective treatment of metastatic breast cancer.     

血尿激酶型纤溶酶原激活剂mRNA水平表达与乳腺癌及其淋巴结转移的关系

目的　研究血尿激酶型纤溶酶原激活剂(uPA)mRNA水平表达与乳腺癌及淋巴结转移的关系及其临床意义。方法　应用荧光定量RT PCR方法,检测60例乳腺良、恶性肿瘤患者血中uPA mRNA水平的表达,分析其与乳腺癌及其淋巴结转移的关系。结果　uPA mRNA表达在18例良性肿瘤患者中16例为阴性,2 例为低表达。在42例乳腺癌患者中,无淋巴结转移的20例中18例为阳性,其中1例为高表达, 5例为中度表达,12 例为低表达,另2例为阴性; 有淋巴结转移的22例均为阳性,其中16 例为高表达,5 例为中度表达,1 例为低表达。乳腺良、恶性肿瘤患者血中uPA mRNA表达差异有显著性意义(P<0.05); 乳腺癌患者中无淋巴结转移者uPA mRNA的表达强度明显低于有淋巴结转移者(P<0.05)。结论　血中uPA mRNA在乳腺癌中的表达明显高于良性肿瘤,其表达强度与乳腺癌淋巴结转移明显相关,可为临床分期及后续治疗提供依据。     

乳腺癌及癌前病变3号染色体短臂杂合性缺失的研究

目的研究乳腺癌及癌前病变中3号染色体短臂（3p）杂合性缺失（loss of heterozygosity,LOH）的发生情况。方法采用聚合酶链式反应及硝酸银染色等方法检测41例原发性乳腺癌及12例癌前病变中3p的11个微卫星位点LOH发生情况;用免疫组化方法检测40例乳腺癌中雌激素受体（ER）、孕激素受体（PR）、脆性组氨酸三联体（fragile histidine triad,FHIT）及人类MutL基因的同源基因（human MutL homologue,hMLH1）的表达情况。结果97％乳腺癌患者发生3p的LOH,检出率较高的位点是D3S1295（53．1％）、D3S1029（43．6％）和D3S1038（52．5％）,分别位于3p14、3021-p22和3p25。D3S1038位点LOH及hMLH1蛋白表达与部分临床病理学参数相关（P〈0．05）。D3S1295的LOH与FHIT蛋白表达负相关（P〈0．05）。癌前病变患者3pLOH发生率为41．7％,检出率较高的位点是D3S1295（27．3％）和D3S1029（16．7％）。最小共同丢失区位于3p14-p25。结论3p14-p25区段可能有与乳腺癌发生发展相关并影响乳腺癌生物学行为的候选抑癌基因,基因的部分缺失可影响其蛋白的表达。     

Breast cancer osteomimicry and its role in bone specific metastasis; an integrative,systematic review of preclinical evidence

Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone.Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016. 4491 potentially relevant citations were retrieved. 63 articles met the inclusion criteria, which were primary studies reporting evidence of molecular factors that have functional roles in predisposing breast cancer bone metastasis in vivo. 12 of those 63 articles that additionally met quality criteria were included in the review. Extracted data were tabulated and key findings that indicated biological mechanisms involved in breast cancer metastasis to bone were synthesised.15 proteins expressed by breast cancer cells were identified as factors that mediate breast cancer bone metastasis: ICAM-1, cadherin-11, osteoactivin, bone sialoprotein, CCN3, IL-11, CCL2, CITED2, CXCR4, CTGF, OPN, CX₃CR1, TWIST1, adrenomedullin and Enpp1. Upregulation or overexpression of one or more of them by breast cancer cells resulted in increased breast cancer metastasis to bone in vivo, except for CCL2 where bone-metastatic cells showed a reduced expression of this factor. All factors identified, here expressed by breast cancer cells, are proteins that are normally expressed in the bone microenvironment and linked to physiologic bone functions. All have a functional role in one of more of the following: cell proliferation and differentiation, bone mineralization and remodelling, cell adhesion and/or chemokine signalling. Six of them (cadherin-11, ICAM-1, OPN, CX₃CR1, CCN3 and osteoactivin) have a reported function in cell adhesion and another eight (CCN3, osteoactivin, Enpp1, IL-11, CTGF, TWIST1, adrenomedullin and CITED2) are reported to be involved in cell proliferation and differentiation.This review collates and synthesises published evidence to increase our understanding of the biology of breast cancer osteomimicry in the development of bone metastasis. Findings of this review suggest that changes in expression of proteins in breast cancer cells that confer osteomimicry facilitate homing to bone to enable the development of bone metastasis.     

Organotropism of Breast Cancer Metastasis

Breast cancer causes mortality by metastasizing to a variety of vital organs, such as bone, lung, brain and liver. Effective therapeutic intervention of this deadly process relies on a better mechanistic understanding of metastasis organotropism. Recent studies have confirmed earlier speculations that metastasis is a non-random process and is dependent on intricate tumor-stroma interactions at the target organ. Both the intrinsic properties of breast cancer cells and the host organ microenvironment are important in determining the efficiency of organ-specific metastasis. Advances in animal modeling, in vivo imaging and functional genomics have accelerated the discovery of important molecular mediators of organ-specific metastasis. A conceptual framework of breast cancer organotropism is emerging and will be instrumental in guiding future efforts in this exciting research field.     

HE、IHC和RT-PCR方法检测乳腺癌腋窝淋巴结转移的对照研究

目的　探讨检测乳腺癌腋窝淋巴结转移较敏感的方法。方法　应用常规HE染色法、细胞角蛋白19(CK19)作为单抗的免疫组化(IHC)SP染色及CK19 mRNA的逆转录聚合酶链反应(RT PCR)3 种方法检测20 例乳腺癌患者共239 个腋窝淋巴结的转移情况。结果　239 个腋窝淋巴结中,HE染色发现3 例患者7 个(2.9%,7/239)有癌转移,均位于level Ⅰ; IHC检测到7例患者13个(5.4%,13/239)有癌转移,其中11个位于level Ⅰ,2个位于level Ⅱ; RT PCR检测到14例患者52 个(21.8%,52/239)有癌转移,其中30 个位于level Ⅰ,22 个位于level Ⅱ。IHC和RT PCR检测证实,HE染色阳性的7 个淋巴结均有癌转移; IHC染色阳性的淋巴结均出现了PCR阳性扩增产物。HE、IHC及RT PCR 3 种检测方法对腋窝淋巴结微转移的检出率分别是0(0/232)、2.6%(6/232)及19.4%(45/232),P<0.05。结论　IHC及RT PCR是较HE检测淋巴结微转移更敏感的方法,而RT PCR较IHC更为敏感,能更准确地反映乳腺癌患者腋窝淋巴结的状况。     

基质细胞衍化因子-1在乳腺肿瘤患者血浆中的表达及其临床意义

目的探讨乳腺肿瘤患者血浆中基质细胞衍化因子-1（SDF-1）的表达及其临床意义。方法使用ELISA法对26例乳腺良性肿瘤患者和52例乳腺癌患者血浆中的SDF-1蛋白水平进行检测。结果乳腺肿瘤患者的血浆中均可以检测到SDF-1蛋白的存在，乳腺癌患者血浆中的SDF-1蛋白表达水平明显高于乳腺良性肿瘤患者（P=0．000）；而在乳腺癌患者中，已有腋窝淋巴结转移者的SDF-1蛋白表达水平又高于无腋窝淋巴结转移者（P=0．036）。结论外周血中SDF-1的表达可能作为一种特异性的恶性肿瘤标志，而且其高表达水平可能与乳腺癌的淋巴结转移状态有关。     

Impact of Clinicopathological Factors on Sensitivity of Axillary Ultrasonography in the Detection of Axillary Nodal Metastases in Patients With Breast Cancer

Background: Ultrasonography and fine-needle aspiration (FNA) are used to evaluate the breast and regional nodes in breast cancer patients. We sought to identify factors influencing the sensitivity of ultrasonography for detection of nodal metastasis.Methods: Patients with a clinically negative axilla who underwent axillary ultrasonography and sentinel lymph node biopsy were included.Results: Of 208 patients, axillary ultrasonography was negative in 180 (86%) and suspicious or indeterminate in 28 (14%). FNA was performed in 22 patients whose findings were indeterminate or suspicious, and 3 were positive for malignancy. Final pathological examinations revealed positive nodes in 53 patients: 39 (22%) of 180 with negative ultrasonographic findings and 14 (50%) of 28 with indeterminate or suspicious ultrasonographic findings (P = .001). Excisional biopsy was more common for patients with indeterminate or suspicious findings on preoperative ultrasonography (P = .038). There were no significant differences in tumor size, histological features, size of nodal metastasis, or number of positive nodes between patients whose ultrasonography findings were negative and those whose findings were indeterminate or suspicious.Conclusions: Ultrasonographically suggested nodal metastasis is associated with the finding of nodal disease on final pathological examination. No significant clinicopathologic criteria were found to impact sensitivity of ultrasonography; however, excisional biopsy for diagnosis may be a confounding variable in subsequent axillary ultrasonography.     

尿微卫星不稳定性研究对膀胱肿瘤诊断的探讨

目的：探讨尿微卫星不稳定性改变(MSI)与膀胱移行细胞癌(TCC)临床病理特征的关系及其在早期诊断中的价值。方法：选择36例TCC患者5个微卫星位点,应用聚合酶链反应-变性聚丙烯酰胺凝胶银染法分析尿微卫星的改变。结果：36例中有22例(61．11%)出现微卫星不稳定性改变(LOH/MSI),并与肿瘤的分期、分级无关(P＞0．05);尿脱落细胞学检查的阳性率为22．22%(8/36),两者相比差异有统计学意义(P＜0．05)。结论：尿沉渣微卫星不稳定性分析对膀胱癌的早期诊断有一定的意义,是尿脱落细胞学检查的重要补充。所选微卫星位点为本地区膀胱癌的进一步研究奠定了基础。