Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL-1), CD44v6 and microvessel density for prostate cancer

被引:75
作者
Ekici, S
Cerwinka, WH
Duncan, R
Gomez, P
Civantos, F
Soloway, MS
Lokeshwar, VB
机构
[1] Univ Miami, Sch Med, Dept Urol, Miami, FL 33101 USA
[2] Univ Miami, Dept Epidemiol, Sch Med, Miami, FL 33152 USA
[3] Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33152 USA
[4] Univ Miami, Sch Med, Dept Cell Biol & Anat, Miami, FL 33152 USA
关键词
prostate cancer; prognostic indicator; hyaluronic acid; hyaluronidase; HYAL-1; CD44v6; microvessel density;
D O I
10.1002/ijc.20368
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Despite the development of nomograms designed to evaluate a prostate cancer (PCa) patient's prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL-1-type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis. CD44 glycoproteins serve as cell surface receptors for HA, and the CD44v6 isoform is associated with tumor metastasis. HYAL-1-type HAase is expressed in tumor cells and, like other HAases, degrades HA into angiogenic fragments. Archival PCa specimens (n = 66) were obtained from patients who underwent radical prostatectomy for clinically localized PCa and had a minimum follow-up of 72 months (range 72-131 months, mean 103 months). For HA, HYAL-1 and CD44v6 staining and MVD determination, a biotinylated HA-binding protein, an anti-HYAL-1 IgG, an anti-CD44v6 IgG and an anti-CD34 IgG were used, respectively. HA and HYAL-1 staining was classified as either low- or high-grade. CD44v6 staining and MVD were evaluated quantitatively and then grouped as either low- or high-grade. Using 72 months as the cut-off limit for evaluating biochemical recurrence, HA, HYAL-1, combined HA-HYAL-1, CD44v6 and MVD staining predicted progression with 96%, 84%, 84%, 68% and 76% sensitivity, respectively. Specificity was, 61% (HA), 80.5% (HYAL-1), 87.8% (HA-HYAL-1), 56.1% (CD44v6) and 61% (MVD). Sensitivity and specificity values for each marker did not change significantly in a subset of 45 patients for whom follow-up of longer than 112 months was available. In univariate analysis using the Cox proportional hazards model, preoperative PSA, Gleason sum, margin status, seminal vesicle, extraprostatic extension (EPE), HA, HYAL-1, HA-HYAL-1 and MVD, but not CD44v6, age and clinical stage, were significant in predicting biochemical recurrence (p < 0.05). In multivariate analysis using stepwise selection, only preoperative PSA (hazard ratio/unit PSA change = 1.086, p < 0.0001), EPE (hazard ratio = 6.22, p = 0.0016) and HYAL-1 (hazard ratio = 8.196, p = 0.0009)/HA-HYAL-1 (hazard ratio = 5.191, p = 0.0021) were independent predictors of biochemical recurrence. HA was an independent predictor of prognosis if HYAL-1 staining inference was not included in the multivariate model. In our retrospective study with 72- to 131-month follow-up, EPE, preoperative PSA and HYAL-1 either alone or together with HA (i.e., combined HA-HYAL-1) were independent prognostic indicators for PCa. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:121 / 129
页数:9
相关论文
共 60 条
[1]   Expression and prognostic value of CD44 standard and variant v3 and v6 isoforms in prostate cancer [J].
Aaltomaa, S ;
Lipponen, P ;
Ala-Opas, M ;
Kosma, VM .
EUROPEAN UROLOGY, 2001, 39 (02) :138-144
[2]   Hyaluronan in peritumoral stroma and malignant cells associates with breast cancer spreading and predicts survival [J].
Auvinen, P ;
Tammi, R ;
Parkkinen, J ;
Tammi, M ;
Ågren, U ;
Johansson, R ;
Hirvikoski, P ;
Eskelinen, M ;
Kosma, VM .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 156 (02) :529-536
[3]   Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy [J].
Blute, ML ;
Bergstralh, EJ ;
Iocca, A ;
Scherer, B ;
Zincke, H .
JOURNAL OF UROLOGY, 2001, 165 (01) :119-125
[4]   Microvessel density in prostate carcinoma [J].
Bono, AV ;
Celato, N ;
Cova, V ;
Salvadore, M ;
Chinetti, S ;
Novario, R .
PROSTATE CANCER AND PROSTATIC DISEASES, 2002, 5 (02) :123-127
[5]   Biochemical staging of prostate cancer [J].
Canto, EI ;
Shariat, SF ;
Slawin, KM .
UROLOGIC CLINICS OF NORTH AMERICA, 2003, 30 (02) :263-+
[6]   The liberation of CD44 [J].
Cichy, J ;
Puré, E .
JOURNAL OF CELL BIOLOGY, 2003, 161 (05) :839-843
[7]   The six hyaluronidase-like genes in the human and mouse genomes [J].
Csoka, AB ;
Frost, GI ;
Stern, R .
MATRIX BIOLOGY, 2001, 20 (08) :499-508
[8]   Microvessel density as a predictor of PSA recurrence after radical prostatectomy - A comparison of CD34 and CD31 [J].
de la Taille, A ;
Katz, AE ;
Bagiella, E ;
Buttyan, R ;
Sharir, S ;
Olsson, CA ;
Burchardt, T ;
Ennis, RD ;
Rubin, MA .
AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 2000, 113 (04) :555-562
[9]  
Delpech B, 2002, ANTICANCER RES, V22, P2423
[10]   Lead times and overdetection due to prostate-specific antigen screening:: Estimates from the European randomized study of screening for prostate cancer [J].
Draisma, G ;
Boer, R ;
Otto, SJ ;
van der Cruijsen, IW ;
Damhuis, RAM ;
Schröder, FH ;
de Koning, HJ .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (12) :868-878