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Background  Hyaluronan, a tumor promoting extracellular matrix polysaccharide, is elevated in malignant epithelial ovarian tumors, and associates with an unfavorable prognosis. To explore possible contributors to the accumulation of hyaluronan, we examined the expression of hyaluronan synthases ( HAS1 ,  HAS2  and  HAS3 ) and hyaluronidases ( HYAL1  and  HYAL2 ), correlated with hyaluronidase enzyme activity hyaluronan content and HAS1–3 immunoreactivity.    Methods  Normal ovaries (n = 5) and 34 serous epithelial ovarian tumors, divided into 4 groups: malignant grades 1+2 (n = 10); malignant grade 3 (n = 10); borderline (n = 4) and benign epithelial tumors (n = 10), were analyzed for mRNA by real-time RT-PCR and compared to hyaluronidase activity, hyaluronan staining, and HAS1–3 immunoreactivity in tissue sections of the same specimens.    Results  The levels of  HAS2  and  HAS3  mRNA ( HAS1  was low or absent), were not consistently increased in the carcinomas, and were not significantly correlated with HAS protein or hyaluronan accumulation in individual samples. Instead, the median of  HYAL1  mRNA level was 69% lower in grade 3 serous ovarian cancers compared to normal ovaries (P = 0.01). The expression of  HYAL1 , but not  HYAL2 , significantly correlated with the enzymatic activity of tissue hyaluronidases (r = 0.5; P = 0.006). An inverse correlation was noted between  HYAL1  mRNA and the intensity of hyaluronan staining of the corresponding tissue sections (r = -0.4; P = 0.025).    Conclusion  The results indicate that in serous epithelial ovarian malignancies  HAS  expression is not consistently elevated but  HYAL1  expression is significantly reduced and correlates with the accumulation of hyaluronan. (233 words)

bmc cancer

Expression of Hyaluronan Synthases (HAS1–3) and Hyaluronidases (HYAL1–2) in Serous Ovarian Carcinomas: Inverse Correlation between HYAL1 and Hyaluronan Content