Strong Stromal Hyaluronan Expression Is Associated with PSA Recurrence in Local Prostate Cancer

Abstract

Objective: HA (hyaluronan) is involved in cell migration, differentiation and cell proliferation, which all are essential to tumour growth. In addition, the cell surface receptor of HA, CD44, is important in cancer cell adhesion, cell migration and tumour neovascularisation. We studied the expression of HA and CD44 and their relationship with other prognostic factors and prostate-specific antigen (PSA) recurrence in local prostate cancer (PC). Material and Methods: 77 PC patients treated with radical prostatectomy were followed-up for a mean of 4 years. HA was detected by using a HA specific probe and CD44 expression was analysed by conventional immunohistochemistry. Results: All specimens expressed HA in tumour stroma and 78% (60/77) of the tumours showed strong stromal expression of HA. The fraction of positively stained specimens for CD44 was 66% (51/77). The strong stromal HA expression was related to perineural infiltration (p = 0.001) and capsule invasion (p = 0.05). No correlation was demonstrated between the stromal HA expression and CD44 expression, preoperative PSA, clinical or pathological T classification, pN status, Gleason grade, seminal vesicle invasion or surgical margin invasion. Reduced CD44 expression was related only to preoperative PSA level (p = 0.008). The PSA recurrence was predicted by strong stromal HA expression, pT classification, seminal vesicle invasion, capsule invasion and surgical margin invasion (p ≤ 0.02 for all). pT classification and seminal vesicle infiltration predicted PSA recurrence free survival (RFS). In the multivariate analysis only the seminal vesicle infiltration was an independent predictor of PSA RFS (p = 0.009). Conclusion: The strong stromal HA expression was related to PSA recurrence, perineural infiltration and seminal vesicle invasion. Those are the factors related to unfavourable prognosis, but the follow-up period of this series is too short to make definitive prognostic conclusions.

Hyaluronic Acid Synthase-1 Expression Regulates Bladder Cancer Growth, Invasion, and Angiogenesis through CD44

“…HAase is an endoglycosidase that breaks HA into fragments, some of which are angiogenic (2). HA levels are elevated in many tumors (3)(4)(5)(6)(7)(8)(9)(10). We have shown that HA levels are elevated in the urine of bladder cancer patients and, together with urinary HAase levels, serve as an accurate diagnostic marker (11)(12)(13).…”

“…In tumor tissues, elevated HA levels are contributed by both the tumor-associated stroma and tumor cells (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). HA synthesis occurs at the plasma membrane by a transmembrane HA synthase (HAS).…”

Enzymatic Depletion of Tumor Hyaluronan Induces Antitumor Responses in Preclinical Animal Models

“…Accumulation of HA has been reported in a wide variety of human tumors, including those of the prostate, colon, breast, stomach, ovary, and pancreas (6)(7)(8)(9)(10)(11)(12). Elevated HA (stromal and/or pericellular staining) in tumor biopsies has been correlated with local invasion, the presence of distal metastasis, higher tumor grade, and poorer overall survival (13).…”

Hyaluronidase Hyal1 Increases Tumor Cell Proliferation and Motility through Accelerated Vesicle Trafficking

“…Altered expression profiles of the Hyal and HAS proteins have been associated with many types of cancers (3)(4)(5)(6)(7). Detection of elevated expression of Hyal1 and concurrent accumulation of HA in biopsies are an indicator of poor prognosis for prostate cancer (8).…”