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The objective of this study was to determine if the level of serum hyaluronan (HA), serum-derived HA-associated protein (SHAP)-HA complex, and urinary trypsin inhibitor (UTI) correlate with the clinical outcome of ovarian cancer patients. The relationship of metalloproteinase and its inhibitor with HA and the SHAP-HA complex was also examined. Serum and urine samples were obtained from 45 patients with ovarian cancer, 22 patients with benign ovarian tumors and 50 healthy women. Concentrations of serum HA and UTI were measured by an inhibitory sandwich enzyme-linked immunosorbent assay, and concentrations of the serum SHAP-HA complex were measured by a sandwich enzymelinked immunosorbent assay. Concentrations of MMP-2, MMP-9 and TIMP-1 were measured by a one-step enzyme immunoassay. The levels of HA, SHAP-HA complex, MMP-9 and TIMP-1 were higher in the ovarian cancer group than in the benign ovarian tumor group. In ovarian cancer patients, the levels of HA, SHAP-HA complex and MMP-9 were higher in the stage III/IV group than in the stage I/II group, and the levels of SHAP-HA complex, MMP-9 and TIMP-1 were higher in the non-responder group than in the responder group. The serum concentration of SHAP-HA complex had a significant correlation with HA, MMP-9 and TIMP-1 in ovarian cancer patients. The patients with elevated SHAP-HA complex had a shorter disease-free survival compared with those with normal levels of SHAP-HA complex. The multiple regression analysis revealed that SHAP-HA complex is the significant independent variable for progression-free survival. The elevated level of SHAP-HA complex may indicate the prognosis of recurrence and reflect the tumor metastasis associated with MMP-9 in ovarian cancer patients.

This report describes the case of the youngest Japanese person to be diagnosed with endocervical clearcell adenocarcinoma. In September 2005, a 17-year-old female adolescent visited a physician because of vaginal bleeding. A cervical tumor was discovered, and the patient was referred to our outpatient department. Vaginal examination showed a bleeding tumor approximately 1.5 cm in size protruding from the cervical os. The cytological finding of the uterine cervix was positive for malignancy, and the histological diagnosis by punch biopsy was clear-cell adenocarcinoma of the uterine cervix. A radical abdominal hysterectomy and pelvic lymphadenectomy were performed on October 30. Macroscopic findings showed a tumor, 1.5 cm in diameter, growing from the right side of the uterine cervix. The pathological diagnosis was clear-cell adenocarcinoma of the cervix (PT1b1NR0M0). The patient was discharged from our hospital without any adjuvant therapy. No signs of recurrence have been detected in the 2-year follow up.

The role of hyaluronan (HA), serum-derived HA-associated protein (SHAP)-HA complex and hyaluronan synthase (HAS) in endometrial carcinomas was investigated. The relationship of metalloproteinase (MMP) and its inhibitor (TIMP) with HA and the SHAP-HA complex was also examined. The expression of HAS1 was related to the depth of myometrial invasion and lymph-vascular space involvement. The serum levels of HA, SHAP-HA complex, MMP-9, and TIMP-1 were increased in related with the depth of myometrial invasion, histological grade and lymph-vascular space involvement. They were also higher in the HAS1-positive group compared to -negative group. The serum concentrations of HA and SHAP-HA complex had a significant correlation with the MMP-9 and TIMP-1. The patients with elevated SHAP-HA complex had the shorter disease-free survival. The multivariate analysis revealed that the SHAP-HA complex was the independent variable for disease-free survival of endometrial cancer patients. In conclusion, the elevation of serum SHAP-HA complex depended on the HAS1 expression and the SHAP-HA complex is a useful marker to predict disease recurrence in endometrial cancer patients. The SHAP-HA complex may promote the lymph-vascular space involvement and the synthesis and activation of MMP-9 and TIMP-1 in the progression of endometrial cancer.