HYAL-1 hyaluronidase: a potential prognostic indicator for progression to muscle invasion and recurrence in bladder cancer.
BACKGROUND
For bladder cancer (BCa) patients undergoing bladder-sparing treatments, molecular markers may aid in accurately predicting progression to muscle invasion and recurrence. Hyaluronic acid (HA) is a glycosaminoglycan that promotes tumor metastasis. Hyaluronoglucosaminidase 1 (HYAL-1)-type hyaluronidase (HAase) promotes tumor growth, invasion, and angiogenesis. Urinary HA and HAase levels are diagnostic markers for BCa.


OBJECTIVE
We evaluated whether HA and HYAL-1 can predict progression to muscle invasion and recurrence among patients with non-muscle-invasive BCa.


METHODS
: Based on tissue availability, tissue microarrays were prepared from a cohort of 178 BCa specimens (144 non-muscle invasive, 34 muscle invasive). Follow-up information was available on 111 patients with non-muscle-invasive BCa (mean follow-up: 69.5 mo); 58 patients recurred and 25 progressed to muscle invasion (mean time to progress: 22.3 mo).


METHODS
HA and HYAL-1 expression was evaluated by immunohistochemistry and graded for intensity and area of staining. Association of HA and HYAL-1 staining with BCa recurrence and muscle invasion was evaluated by univariate and multivariate models.


CONCLUSIONS
HA and HYAL-1 expression correlated with tumor grade, stage, and multifocality (p<0.05). In non-muscle-invasive BCa specimens, HYAL-1 staining was higher (234.3+/-52.2; 200.6+/-61.4) if patients experienced progression to muscle invasion or recurrence when compared with no progression or recurrence (164.1+/-48.2; 172.1+/-57; p<0.001). HA staining correlated with muscle invasion (p<0.001). In univariate analysis, age (p=0.014), multifocality (p=0.023), and HYAL-1 staining (p<0.001) correlated with muscle invasion, whereas only HYAL-1 correlated with recurrence (p=0.013). In multivariate analysis, HYAL-1 significantly associated with muscle invasion (p<0.001; 76.8% accuracy) and recurrence (p=0.01; 67.8% accuracy).


CONCLUSIONS
HYAL-1 is a potential prognostic marker for predicting progression to muscle invasion and recurrence.
Kramer
Mario W
MW
Department of Urology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
Golshani
Roozbeh
R
Merseburger
Axel S
AS
Knapp
Judith
J
Garcia
Alfredo
A
Hennenlotter
Joerg
J
Duncan
Robert C
RC
Soloway
Mark S
MS
Jorda
Merce
M
Kuczyk
Marcus A
MA
Stenzl
Arnulf
A
Lokeshwar
Vinata B
VB
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis; D006821:Hyaluronoglucosaminidase / Q000032:analysis*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D009130:Muscle, Smooth / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology / Q000628:therapy
D014408:Biomarkers, Tumor; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase