Biomarker discovery in urogenital cancer.
Novel approaches for the early detection of urogenital cancers are urgently needed. Metastatic renal cell carcinoma (RCC) has a poor prognosis and unpredictable course and to date there are no molecular markers that reliably protect RCC outcome. A novel kidney cancer marker, carbonic anhydrase IX (CA IX), was investigated as an independent prognostic factor for survival for patients with metastatic RCC. In patients with non-metastatic RCC low CAIX predicted a worse outcome similar to patients with metastatic disease and overall CAIX expression decreased with development of metastasis. CAIX reflects significant changes in tumour biology, which may be used to predict clinical outcome and identify high-risk patients for adjuvant-targeted therapies. With regard to prostate cancer there are a number of putative biomarkers, although there are limited studies providing clinical correlations in humans. Potential biomarkers include caveolin-1, p-Akt, p27, the met oncogene, Ki67 (MIB-1), 8q24 over-expression, polycomb protein EZH2, plasma TGF-B1 and IL-6 among others. The laboratory has concentrated on the Prostate Stem Cell Antigen (PSCA) which is increased in patients with more aggressive features, that is higher Gleason grade and higher stage. Highest expression is seen in metastatic lesions to bone and staining for PSCA may predict for disease progression or recurrence. Also promising is the finding reported by the group that expression of p27 in radical prostatectomy specimens correlates with biochemical recurrence. Loss of p27 (defined as absent expression in more than 70% of the specimen) is an independent predictor of recurrence among all patients and among the sub-set with organ confined and extra-capsular disease. The data also shows that p27 can predict outcome among patients with positive surgical resection margins. As with other biomarkers, major questions still to be addressed is the requirement for universal application with uniform scoring and the need for prospective studies in randomized clinical trials.
Said
Jonathan
J
Department of Pathology and Laboratory Medicine and Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. jsaid@mednet.ucla.edu
D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers; D014408:Biomarkers, Tumor; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000378:metabolism; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism; D016896:Treatment Outcome; D014565:Urogenital Neoplasms / Q000175:diagnosis* / Q000378:metabolism*
D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D018809:Proliferating Cell Nuclear Antigen; C413374:p27 antigen; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases