Impact of Caveolin-1 Expression on the Prognosis of Transitional Cell Carcinoma of the Upper Urinary Tract

This study aimed to investigate the relationship of caveolin-1 expression with prognosis in patients with transitional cell carcinoma of the upper urinary tract (TCC-UUT). Formalin-fixed, paraffin-embedded tissue sections of TCC-UUT from 98 patients, who had undergone radical nephroureterectomy, were stained immunohistochemically using antibodies against caveolin-1. The expression pattern of caveolin-1 was compared with the clinicopathological variables. The caveolin-1 expression was significantly correlated with T stage (p<0.001) and grade (p=0.036). The survival rate of patients with caveolin-1 positive tumors was significantly lower than that of patients with caveolin-1 negative tumors (p<0.0001). The univariate analyses identified T stage, grade, and caveolin-1 expression as significant prognostic factors for cancer-specific survival, whereas the multivariate analyses indicated that T stage and caveolin-1 expression were independent prognostic factors. These results show that the increased expression of caveolin-1 is associated with tumor progression and poor prognosis in TCC-UUT, suggesting that caveolin-1 may play an important role in the progression of TCC-UUT.

[1]  Carsten Wunderlich,et al.  Caveolae and caveolin in transmembrane signaling: Implications for human disease. , 2006, Cardiovascular research.

[2]  S. Okushiba,et al.  Overexpression of caveolin‐1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage , 2002, Cancer.

[3]  M. Dietel,et al.  Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas. , 2001, The American journal of pathology.

[4]  M. Climent,et al.  Conservative elective treatment of upper urinary tract tumors: a multivariate analysis of prognostic factors for recurrence and progression. , 2003, The Journal of urology.

[5]  M. Lisanti,et al.  The Caveolin genes: from cell biology to medicine , 2004, Annals of medicine.

[6]  C. Balch,et al.  AJCC Cancer Staging Manual. 6th ed , 2002 .

[7]  J. Minna,et al.  Different Roles for Caveolin-1 in the Development of Non-Small Cell Lung Cancer versus Small Cell Lung Cancer , 2004, Cancer Research.

[8]  M. Robinson,et al.  Caveolin-1 expression is associated with high-grade bladder cancer. , 2001, Urology.

[9]  Lawrence D. True,et al.  The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder , 1998 .

[10]  M. Lisanti,et al.  Upregulation of caveolin‐1 and caveolae organelles in Taxol‐resistant A549 cells , 1998, FEBS letters.

[11]  H. Doihara,et al.  Caveolin-1 as Tumor Suppressor Gene in Breast Cancer , 2003, Surgery Today.

[12]  J. Couet,et al.  Role of caveolin-1 in etoposide resistance development in A549 lung cancer cells , 2004, Cancer biology & therapy.

[13]  H. Kanetake,et al.  Expression of cyclooxygenase-2 and EP4 receptor in transitional cell carcinoma of the upper urinary tract. , 2005, The Journal of urology.

[14]  C. Compton,et al.  AJCC Cancer Staging Manual , 2002, Springer New York.

[15]  L. Truong,et al.  Caveolin-1 expression in clinically confined human prostate cancer: a novel prognostic marker. , 1999, Cancer research.

[16]  J. Engelman,et al.  Genes encoding human caveolin‐1 and ‐2 are co‐localized to the D7S522 locus (7q31.1), a known fragile site (FRA7G) that is frequently deleted in human cancers , 1998, FEBS letters.

[17]  L. Ellison,et al.  Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. , 2000, The Journal of urology.

[18]  S. Knuutila,et al.  Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array , 2002, Oncogene.

[19]  David S. Park,et al.  Loss of caveolin-1 gene expression accelerates the development of dysplastic mammary lesions in tumor-prone transgenic mice. , 2003, Molecular biology of the cell.

[20]  F. Mostofi,et al.  The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. , 1998, The American journal of surgical pathology.

[21]  Sun-Ja Kim,et al.  Increased expression of caveolin‐1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma , 2004, BJU international.

[22]  Richard G. W. Anderson,et al.  Multiple Functions of Caveolin-1* , 2002, The Journal of Biological Chemistry.

[23]  M. Lisanti,et al.  Expression of caveolin-1 and caveolin-2 in urothelial carcinoma of the urinary bladder correlates with tumor grade and squamous differentiation. , 2003, American journal of clinical pathology.

[24]  T. Timme,et al.  Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells , 1998, Nature Medicine.

[25]  M. Lisanti,et al.  Caveolins, a Family of Scaffolding Proteins for Organizing “Preassembled Signaling Complexes” at the Plasma Membrane* , 1998, The Journal of Biological Chemistry.

[26]  S. Fine,et al.  Elevated expression of caveolin-1 in adenocarcinoma of the colon. , 2001, American journal of clinical pathology.

[27]  S. Okushiba,et al.  Difference of caveolin-1 expression pattern in human lung neoplastic tissue. Atypical adenomatous hyperplasia, adenocarcinoma and squamous cell carcinoma. , 2004, Cancer letters.

[28]  M Dietel,et al.  Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene. , 2001, The American journal of pathology.

[29]  Shu-Chun Lin,et al.  The biphasic differential expression of the cellular membrane protein, caveolin-1, in oral carcinogenesis. , 2003, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[30]  J. Lee,et al.  bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. , 1995, Cancer research.

[31]  S. Scherer,et al.  Identification of a 1300 kilobase deletion unit on chromosome 7q31.3 in invasive epithelial ovarian carcinomas , 1997, Oncogene.