Hyaluronidase (ph-20) expression in normal and neoplastic breast tissue: a novel prognostic marker?

DJ Beech, M.D., AK Madan, M.D., Nan Deng, MS

Department of Surgery, Section of Surgical Oncology, The University of Tennessee, Memphis, TN

Introduction: Breast cancer is a leading cause of cancer-related death in the United States. Previous investigations have reported that elevated levels of hyaluronidase (PH-20) correlate with tumor metastasis in prostate, laryngeal, and breast cancers. Tumor metastasis involves a sequence of interrelated steps of which penetration beyond the basement membrane is an essential component. Hyaluronic Acid (HA) is a major structural component of the complex proteoglycans found in extracellular matrices and basement membranes. Hyaluronidase (PH-20) degrades HA and results in disruption of basement membrane integrity and possibly tumor dissemination. Our investigation characterizes PH-20 expression in normal and malignant breast tissue. Materials and Methods: Total RNA was extracted from human samples of normal and neoplastic breast tissue (n=51). RT-PCR was used to determine the relative level of PH-20 in each specimen. Results: PH-20 was detected in 41/51 (80.4%) of the specimens evaluated. PH-20 was present in 12/12 (100%) of normal breast tissue; 8/12 (66%) DCIS; 13/13 (100%) of invasive cancer and 8/14 (57.1%) of metastatic breast cancer specimens. Increased levels of PH-20 were noted in metastatic breast cancer to lymph nodes compared to DCIS and invasive breast cancer. Stratification by race revealed that African-American women had higher levels of PH-20 than Caucasians. Conclusion: Increased levels of PH-20 were noted in invasive and metastatic breast cancer compared to DCIS. Tumors from African-American women demonstrated higher levels of PH-20 than Caucasians. Increased levels of PH-20 may contribute to early invasion and metastasis of breast cancer.

KEY WORDS: Hyaluronidase, breast cancer, metastasis, .

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Diagnostic Markers.