Tissue Array-Based Predictions of Pathobiology, Prognosis, and Response to Treatment for Renal Cell Carcinoma Therapy

Renal cell carcinoma is the most lethal of the common urologic malignancies, with ∼40% of patients eventually dying of cancer progression. Approximately one third of patients present with metastatic disease, and up to 40% treated for localized disease have a recurrence. Historically, clinical factors have been used as prognostic markers for patients with renal cell carcinoma. Recent advances in the understanding of the pathogenesis, behavior, and molecular biology of renal cell carcinoma have paved the way for developments that may enhance early diagnosis, better predict tumor prognosis, and improve survival for renal cell carcinoma patients. Furthermore, reliable predictive factors are essential for the stratification of patients into clinically meaningful categories, which can be used to provide patients with counseling regarding prognosis, select treatment modalities, and determine eligibility for clinical trials. This has led to the creation of integrated staging systems that predict outcome by combining pathological and clinical variables. Although staging has been improved with the development of integrated systems, molecular tumor markers are expected to revolutionize the staging of renal cell carcinoma in the future. The development of methods based on gene and tissue arrays has created a powerful tool for evaluating hundreds to thousands of tumors simultaneously with histologic, immunohistochemical, and chromosomal analyses. Gene array analysis permits rapid molecular profiling, and tissue arrays enable the analysis of protein expression profiles on specimens to determine their potential clinical significance and role in renal cell carcinoma biology. This article reviews the tissue array-based predictors of pathobiology, prognosis, response to treatment, and potential molecular targets for therapy of renal cell carcinoma.

[1]  J. Lam,et al.  Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy. , 2005, The Journal of urology.

[2]  S. Signoretti,et al.  Carbonic Anhydrase IX (CAIX) expression predicts for renal cell cancer (RCC) patient response and survival to IL-2 therapy. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  S. Horvath,et al.  Prognostic value of carbonic anhydrase IX and KI67 as predictors of survival for renal clear cell carcinoma. , 2004, The Journal of urology.

[4]  F. Peale,et al.  Expression of vascular endothelial growth factor, hypoxia inducible factor 1α, and carbonic anhydrase IX in human tumours , 2004, Journal of Clinical Pathology.

[5]  S. Horvath,et al.  Epithelial Cell Adhesion Molecule (KSA) Expression , 2004, Clinical Cancer Research.

[6]  F. Erdoğan,et al.  Prognostic significance of morphologic parameters in renal cell carcinoma , 2004, International journal of clinical practice.

[7]  S. Horvath,et al.  1651: Molecular Prognostic Modeling Using Protein Expression Profile in Clear Cell Renal Carcinoma , 2004 .

[8]  C. Lamers,et al.  A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients , 2004, British Journal of Cancer.

[9]  P. Rehak,et al.  Steroid hormone receptor expression in renal cell carcinoma: an immunohistochemical analysis of 182 tumors. , 2004, The Journal of urology.

[10]  V. Bilim,et al.  Impact of frequent Bcl-2 expression on better prognosis in renal cell carcinoma patients , 2004, British Journal of Cancer.

[11]  R. Figlin,et al.  Validation of an integrated staging system toward improved prognostication of patients with localized renal cell carcinoma in an international population. , 2003, The Journal of urology.

[12]  L. Campbell,et al.  Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma , 2003, British Journal of Cancer.

[13]  R. Figlin,et al.  Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. , 2003, The Urologic clinics of North America.

[14]  M. Dimopoulos,et al.  Prognostic significance of CA 125, CD44, and epithelial membrane antigen in renal cell carcinoma. , 2003, Urology.

[15]  J. Cerhan,et al.  Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma. , 2003, The Journal of urology.

[16]  G. Landberg,et al.  Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray , 2003, British Journal of Cancer.

[17]  S. Horvath,et al.  Correlation of Ki-67 and gelsolin expression to clinical outcome in renal clear cell carcinoma. , 2003, Urology.

[18]  Steve Horvath,et al.  Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[19]  R. Figlin,et al.  Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  J. Cheville,et al.  An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. , 2002, The Journal of urology.

[21]  Kazuki Kobayashi,et al.  VHL tumor suppressor gene alterations associated with good prognosis in sporadic clear-cell renal carcinoma. , 2002, Journal of the National Cancer Institute.

[22]  Bin Yang,et al.  CD10 facilitates the diagnosis of metastatic renal cell carcinoma from primary adrenal cortical neoplasm in adrenal fine‐needle aspiration , 2002, Diagnostic cytopathology.

[23]  R. Motzer,et al.  Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear-cell histology. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  M. Probst-Kepper,et al.  CXCR4/CXCL12 expression and signalling in kidney cancer , 2002, British Journal of Cancer.

[25]  G. Semenza,et al.  HIF-1 and tumor progression: pathophysiology and therapeutics. , 2002, Trends in molecular medicine.

[26]  T. Poggio,et al.  Multiclass cancer diagnosis using tumor gene expression signatures , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[27]  N. Munshi,et al.  Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. , 2001, The New England journal of medicine.

[28]  R. Figlin,et al.  Nephrectomy and interleukin-2 for metastatic renal-cell carcinoma. , 2001, The New England journal of medicine.

[29]  A. Belldegrun,et al.  The changing natural history of renal cell carcinoma. , 2001, The Journal of urology.

[30]  J. Welsh,et al.  Molecular classification of human carcinomas by use of gene expression signatures. , 2001, Cancer research.

[31]  R. Sylvester,et al.  Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial , 2001, The Lancet.

[32]  R. Figlin,et al.  Validation of the ucla integrated staging system for patients with renal cell carcinoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  K. Furge,et al.  Gene expression profiling of clear cell renal cell carcinoma: Gene identification and prognostic classification , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[34]  M. Kattan,et al.  A postoperative prognostic nomogram for renal cell carcinoma. , 2001, The Journal of urology.

[35]  R. Figlin,et al.  Improved prognostication of renal cell carcinoma using an integrated staging system. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  W. Sly,et al.  Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer. , 2001, The American journal of pathology.

[37]  G. Semenza,et al.  Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. , 2000, Cancer research.

[38]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[39]  G. Roos,et al.  Prognostic Significance of the Heidelberg Classification of Renal Cell Carcinoma , 1999, European Urology.

[40]  S. Saga,et al.  MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas , 1999, British Journal of Cancer.

[41]  M Mazumdar,et al.  Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  N. Bander,et al.  Reduced expression of beta-subunit of Na,K-ATPase in human clear-cell renal cell carcinoma. , 1999, The Journal of urology.

[43]  V. Paradis,et al.  CD44 is an independent prognostic factor in conventional renal cell carcinomas. , 1999, The Journal of urology.

[44]  C. Wykoff,et al.  The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis , 1999, Nature.

[45]  J L Warren,et al.  Rising incidence of renal cell cancer in the United States. , 1999, JAMA.

[46]  T. Sejima,et al.  Expression of Bcl-2, p53 Oncoprotein, and Proliferating Cell Nuclear Antigen in Renal Cell Carcinoma , 1999, European Urology.

[47]  R. Figlin Renal cell carcinoma: management of advanced disease. , 1999, The Journal of urology.

[48]  S. Larson,et al.  Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[49]  J. Schalken,et al.  Decreased expression of alpha-catenin is associated with poor prognosis of patients with localized renal cell carcinoma. , 1998, International Journal of Cancer.

[50]  J. Kononen,et al.  Tissue microarrays for high-throughput molecular profiling of tumor specimens , 1998, Nature Medicine.

[51]  K. Aozasa,et al.  Prognostic factors of renal cell carcinoma: A multivariate analysis , 1998, Journal of surgical oncology.

[52]  J. Schalken,et al.  Decreased expression of α‐catenin is associated with poor prognosis of patients with localized renal cell carcinoma , 1997 .

[53]  Holger Moch,et al.  The Heidelberg classification of renal cell tumours , 1997, The Journal of pathology.

[54]  E. Stanbridge,et al.  Identification of the MN/CA9 protein as a reliable diagnostic biomarker of clear cell carcinoma of the kidney. , 1997, Cancer research.

[55]  R. Kettmann,et al.  Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships. , 1996, Genomics.

[56]  N. Bander,et al.  Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[57]  B. Delahunt,et al.  Nucleolar organizer regions and prognosis in renal cell carcinoma , 1991, The Journal of pathology.

[58]  D. Trump,et al.  Prognostic factors for survival in patients with recurrent or metastatic renal cell carcinoma. , 1988, Cancer research.

[59]  D. Ruiter,et al.  Monoclonal antibody G 250 recognizes a determinant present in renal‐cell carcinoma and absent from normal kidney , 1986, International journal of cancer.

[60]  M. Atkins,et al.  Systemic therapy for renal cell carcinoma. , 2005, Cancer chemotherapy and biological response modifiers.

[61]  W. Isaacs,et al.  Cadherin-6: a new prognostic marker for renal cell carcinoma. , 2004, The Journal of urology.

[62]  A. Jemal,et al.  Cancer Statistics, 2004 , 2004, CA: a cancer journal for clinicians.

[63]  Adrian L. Harris,et al.  Hypoxia — a key regulatory factor in tumour growth , 2002, Nature Reviews Cancer.

[64]  Van,et al.  A gene-expression signature as a predictor of survival in breast cancer. , 2002, The New England journal of medicine.

[65]  C. Niederberger,et al.  What nonresponse to intracavernous injection really indicates: a determination by quantitative analysis. , 2002, The Journal of urology.

[66]  E. Lander,et al.  Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[67]  P. Lipponen,et al.  Value of Ki-67 immunolabelling as a prognostic factor in prostate cancer. , 1997, European urology.

[68]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[69]  P. Bassi,et al.  Prognostic factors in renal cell carcinoma. , 1988, European urology.