Metastasis Markers in Bladder Cancer: A Review of the Literature and Clinical Considerations

Gontero, Paolo; Banisadr, Sarvenaz; Frea, Bruno; Brausi, Maurizio

doi:10.1016/j.eururo.2004.04.001

Cited by 67 publications

(56 citation statements)

References 159 publications

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“…The pathways into the lymphatic or vascular system were expected to be promoted by stimulation of lymphangiogenesis or angiogenesis. However, various other processes, including migration, invasion, adhesion, and growth at metastatic sites, are necessary to form the metastatic tumor and influence survival, and these processes are regulated by numerous factors (9,10). Therefore, we speculate that the predictive values of LVD and MVD for clinical outcome are dependent on the malignant potential of cancer cells, factors produced by cancer cells or released by stromal tissues, and organ microenvironment at metastatic sites.…”

Section: Discussionmentioning

confidence: 99%

“…However, this superficial carcinoma often recurs and invades the muscle after the initial treatment; such progression is associated with a high risk of subsequent metastasis and poor survival (7,8). Various growth factors and molecules have been reported to be associated with tumor growth, progression, and survival in bladder cancer (9,10 thought to be one of the most useful prognostic markers for disease development, grade, recurrence-free survival, and overall survival (11 -13). In contrast, the clinical and pathologic significance of lymphangiogenesis (lymph vessel density, LVD) in human bladder cancer tissues are yet to be investigated.…”

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confidence: 99%

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Lymphangiogenesis and Angiogenesis in Bladder Cancer: Prognostic Implications and Regulation by Vascular Endothelial Growth Factors-A, -C, and -D

Miyata

Kanda

Ohba

et al. 2006

Clinical Cancer Research

114

119

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Purpose: Lymph vessel density (LVD) and microvessel density (MVD) correlate with the malignant potential of tumors and patient survival. Vascular endothelial growth factors (VEGF)-A, VEGF-C, and VEGF-D could modulate LVD and MVD. We investigated the clinical and prognostic significance of LVD and MVD on lymphangiogenic and angiogenic function of VEGF-A,VEGF-C, and VEGF-D in human bladder cancer. Experimental Design: We reviewed tissue samples from patients with nonmetastatic bladder cancer who had undergone transurethral resections (n = 126). The densities of D2-40-positive vessels (LVD) and CD34-positive vessels (MVD) were measured by a computer-aided image analysis system. Expression of VEGF-A, VEGF-C, and VEGF-D was examined by immunohistochemistry; survival analyses and their independent roles were investigated using multivariate analysis models. Results: LVD was associated with tumor grade but not with pTstage. LVD was associated with metastasis-free survival (log rank P = 0.039), but was not an independent prognostic factor. Although MVD affected survival, the combination of high LVD and high MVD in tumors was an independent predictor of metastasis-free survival. Although VEGF-C expression was positively associated with both LVD and MVD,VEGF-D was associated only with LVD.VEGF-A expression was associated with MVD in univariate analysis, however, it was not an independent factor. Conclusions: Lymphangiogenesis and angiogenesis influence metastasis-free survival, and are regulated by VEGF-C and/or VEGF-D. Our results suggest that LVD and MVD are useful tools for the selection of postoperative management and treatment strategies in patients with bladder cancer.Metastatic dissemination of the primary tumor is an important factor that negatively affects the prognosis in most malignancies and neovascularization (angiogenesis) plays a critical role in tumor growth and systemic dissemination of cancer cells (1). As such, much attention has been focused on the pathologic significance and detailed mechanism of the vascular system and angiogenesis in cancers. In addition to dissemination of cancer cells via the bloodstream, the lymphatic system is also thought to play an important role in tumor cell dissemination.Indeed, metastatic spread to regional lymph nodes is an early step in the systemic dissemination of tumors, and lymph node metastasis is generally associated with poor survival (2, 3). However, the clinical significance of the de novo formation of lymphatic capillaries (lymphangiogenesis) and its regulation in cancer remains unclear, largely because specific endothelial markers for lymphatic vessels are unknown and lymphatic vessels cannot be detected in human cancer tissues (4). In recent years, several new specific antibodies for lymphatic endothelial cells have been developed and used to investigate the clinical and pathologic significance of lymphangiogenesis in various cancers (5).Bladder cancer is the second most common malignant tumor of the urogenital region. This tumor is associated with fr...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Lymphangiogenesis and Angiogenesis in Bladder Cancer: Prognostic Implications and Regulation by Vascular Endothelial Growth Factors-A, -C, and -D

Miyata

Kanda

Ohba

et al. 2006

Clinical Cancer Research

114

119

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“…Stein et al have performed an exhaustive review of a variety of biological markers reported to have prognostic value (336 ). More recently, p53 and other cell cycle control genes (337,338 ), chorionic gonadotropin, beta polypeptide (CGB; hCG␤) gene transcripts (339 ), and various cell matrix and adhesion proteins and differentially expressed genes (early vs late stage tumors) have all been reported to have prognostic value (340 ). However, at the present time, none of these markers have yet been validated for use in routine patient care.…”

Section: Role Of Urine Markers In Early Detection Of Bladder Cancermentioning

confidence: 99%

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Liver, Bladder, Cervical, and Gastric Cancers

et al. 2010

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Background: Updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. Methods: Published reports relevant to use of tumor markers for 4 cancer sites—liver, bladder, cervical, and gastric—were critically reviewed. Results: α-Fetoprotein (AFP) may be used in conjunction with abdominal ultrasound for early detection of hepatocellular carcinoma (HCC) in patients with chronic hepatitis or cirrhosis associated with hepatitis B or C virus infection. AFP concentrations >200 μg/L in cirrhotic patients with typical hypervascular lesions >2 cm in size are consistent with HCC. After a diagnosis of HCC, posttreatment monitoring with AFP is recommended as an adjunct to imaging, especially in the absence of measurable disease. Although several urine markers have been proposed for bladder cancer, none at present can replace routine cystoscopy and cytology in the management of patients with this malignancy. Some may, however, be used as complementary adjuncts to direct more effective use of clinical procedures. Although carcinoembryonic antigen and CA 19-9 have been proposed for use gastric cancer and squamous cell carcinoma antigen for use in cervical cancer, none of these markers can currently be recommended for routine clinical use. Conclusions: Implementation of these recommendations should encourage optimal use of tumor markers for patients with liver, bladder, cervical, or gastric cancers.

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“…Several genetic lesions that provide cues for cell transformation, increased cell growth, migration and invasion in bladder cancer have been identified. These include mutations or alterations in expression of p53, p16, pRb, p21, c-erb B-2, MMP-2 and -9, uPAR, PD-ECGF and bFGF (Chatterjee et al, 2004;Gontero et al, 2004;Buscarini et al, 2005). Cumulative increase in these genetic defects also provides prognostic assessment for disease outcome.…”

Section: Introductionmentioning

confidence: 99%

EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival

et al. 2005

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Metastasis Markers in Bladder Cancer: A Review of the Literature and Clinical Considerations

Cited by 67 publications

References 159 publications

Lymphangiogenesis and Angiogenesis in Bladder Cancer: Prognostic Implications and Regulation by Vascular Endothelial Growth Factors-A, -C, and -D

Lymphangiogenesis and Angiogenesis in Bladder Cancer: Prognostic Implications and Regulation by Vascular Endothelial Growth Factors-A, -C, and -D

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Liver, Bladder, Cervical, and Gastric Cancers

EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival

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