Quantification of angiogenesis by the Chalkley method and its prognostic significance in epithelial ovarian cancer.

AIM: The aim of the present study was to clarify prognostic role of angiogenesis in epithelial ovarian cancer. METHODS: Quantification of angiogenesis was performed by the Chalkley method after immunostaining of 175 epithelial ovarian cancer specimens with an antibody against CD34. RESULTS: The Chalkley count was categorised into two groups according to the median value: low <8 or high > or =8. The low Chalkley count correlated significantly with serous and clear cell histological subtype of the tumour (p<0.0005), whereas there existed no association with FIGO (International Federation of Gynecology and Obstetrics) stage, histological grade, presence of primary residual tumour, age at diagnosis, or chemotherapy response. In univariate analysis, the high Chalkley count predicted poor overall survival in the subgroup of patients with FIGO stages III-IV tumours (p=0.007) but not in the entire study cohort. However, in multivariate analysis, the Chalkley count was found to be an independent predictor of death from ovarian cancer in the entire study cohort (p=0.044, RR=1.50, 95% CI 1.01-2.21) as well as in the subgroup of FIGO stages III-IV tumours (p=0.046, RR=1.58, 95% CI 1.01-2.46) together with the presence of primary residual tumour (p<0.0005, RR=5.10, 95% CI 3.02-8.62, and p=0.002, RR=4.28, 95% CI 1.34-13.73, respectively). CONCLUSIONS: The Chalkley count seems to be suitable for evaluation of angiogenesis and to have prognostic significance in ovarian cancer.

Prognostic significance of iNOS in epithelial ovarian cancer.

OBJECTIVE: To study the association of inducible nitric oxide synthase (iNOS) expression with clinicopathological factors and prognosis in epithelial ovarian cancer. METHODS: The study included 301 patients with primary epithelial ovarian cancer. iNOS expression was evaluated by immunohistochemistry using a mouse monoclonal antibody. RESULTS: iNOS positivity was observed as granular deposits in the cancer cell cytoplasm. The mean percentage of iNOS-positive cells was 50% in primary tumors (n=301), and 62% in metastatic lesions (n=43). iNOS expression correlated significantly with histological subtype of the tumor, as high (> 70%) iNOS expression was observed in mucinous tumors (p=0.009). Poorly differentiated tumors showed a tendency to low (< or = 70%) iNOS expression but without statistical significance. Low iNOS expression associated also significantly with large primary residual tumor (p=0.007) and tumor recurrence (p=0.04). The 10-year prognosis of the patients with high iNOS expression was better in disease-related survival (DRS) (p=0.009). However, in multivariate analysis only FIGO stage, primary residual tumor, and grade of the tumor were independent prognostic factors for DRS, but not the iNOS expression. CONCLUSIONS: A major proportion of human epithelial ovarian cancers expressed iNOS. The positive expression was an indicator of better disease-related survival. However, iNOS positivity could not overcome the importance of clinicopathological factors in prediction of prognosis.

Prognostic significance of matrix metalloproteinase-7 in epithelial ovarian cancer and its relation to beta-catenin expression.

We investigated the expression and prognostic significance of matrix metalloproteinase (MMP) -7, its relation to beta-catenin expression and clinicopathological factors in epithelial ovarian cancer. The expression of MMP-7 was analyzed immunohistochemically in a series of 284 primary epithelial ovarian cancers, their 36 metastases and 8 normal ovaries. In cancers with endometrioid histology, a high percentage area of MMP-7 expression and an intense MMP-7 signal was significantly associated with nuclear positivity of beta-catenin in cancer cells (p = 0.003, chi2 = 8.853 and p = 0.030, chi2 = 4.713, respectively). In all tumors and nonendometrioid subgroup, a low percentage area of MMP-7 positive tumor cells was significantly correlated with a high histological grade of the tumor (p = 0.003 and 0.005, respectively), in all tumors also with advanced stage of the tumor (p = 0.002) and large primary residual tumor (p = 0.005). A 10-year disease-related survival (DRS) was significantly better when the percentage area of MMP-7 expression in cancer cells was high, when compared to low (p = 0.0008). A high percentage area of intense MMP-7 signal in cancer cells predicted a significantly more favorable DRS and recurrence-free survival (RFS) (p = 0.0003 and 0.0052, respectively). In multivariate analysis, a high percentage area of intense MMP-7 signal in tumor cells was an independent prognostic factor, predicting favorable DRS and RFS. The present study showed that intense MMP-7 signal in tumor cells is an independent prognostic factor predicting better survival in epithelial ovarian cancer.

CD44 expression indicates favorable prognosis in epithelial ovarian cancer.

PURPOSE: The purpose of this study was to investigate the expression and prognostic significance of CD44 in epithelial ovarian cancer. EXPERIMENTAL DESIGN: We analyzed the expression of CD44 by immunohistochemistry in 307 epithelial ovarian cancers and evaluated its relation to hyaluronan, clinicopathological factors, and prognosis. RESULTS: Fifty-one percent of the tumors had a high proportion of CD44-positive cells (i.e., >/==" BORDER="0">10%), and this high CD44 expression was significantly associated with cancer cell-associated hyaluronan, well-differentiated tumor, mucinous histological type, and early stage of the tumor. High CD44 expression predicted better 5-year overall survival (50% versus 22%) and recurrence-free survival (70% versus 34%) in the univariate analyses (P < 0.00005 for both). In the Cox multivariate analyses, the independent predictors of overall survival at 5 years were primary residual tumor (P < 0.0005), International Federation of Gynecologists and Obstetricians (FIGO) stage (P = 0.001), histological grade (P = 0.014), adjuvant chemotherapy (P = 0.004), and stromal hyaluronan level (P < 0.0005), but not CD44. However, the expression of CD44 (P = 0.04) and stromal hyaluronan (P = 0.005) were both independent predictors of recurrence-free survival at 5 years, together with the size of the primary residual tumor (P < 0.0005) and histological type (P = 0.043). CONCLUSIONS: The relatively frequent ectopic expression of CD44 on ovarian cancer cells is thus related to well-differentiated, early-stage tumor and long survival of the patients. Thus, whereas CD44-expressing cancer cells may adhere and implant to the hyaluronan-positive mesothelium, at least in model systems, high expression of CD44 in the tumor does not bring about an unfavorable prognosis.

Obstetric outcome in women with endometriosis--a matched case-control study.

BACKGROUND: Immunological deficiencies, altered angiogenic activity, infiltrative potential and growth factors are plausible factors behind endometriosis. The aim of this study was to determine whether endometriosis interferes with the course or outcome of pregnancy. STUDY DESIGN: In this matched case-control study, we analyzed obstetric outcome among 137 women with endometriosis and 137 controls matched as regards IVF procedures and parity who gave singleton births at Kuopio University Hospital between January 1994 and December 2000. In affected women, the diagnosis was histologically verified, whereas the controls were eligible for the study only if they had undergone laparoscopy/tomy in connection with tubal sterilization, or infertility unrelated to endometriosis. RESULTS: No statistically significant differences were detected in reproductive risk factors in women with endometriosis, with the exception of mean maternal age (31.2 years in the cases vs. 34 years in the controls). The mean birth weight (+/-SD) among those delivering at term (>37 completed weeks) was 3,600 (+/-542) g in the control group and 3,547 (+/-456) g in the study group. Placental weight was comparable in both groups. Overall pregnancy characteristics and pregnancy outcome measures were similar in women affected by endometriosis when compared with the control group. CONCLUSIONS: Any potential negative effect of endometriosis on obstetric outcome was undetectable.