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 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.

Versican in epithelial ovarian cancer: relation to hyaluronan, clinicopathologic factors and prognosis.

Versican, a proteoglycan previously reported to increase in other malignant tumours, was studied immunohistochemically in 299 primary epithelial ovarian cancers, their 43 metastases and 6 normal ovaries to evaluate its prognostic value and relation to hyaluronan, another extracellular matrix molecule increased in cancer and a binding partner of versican. The stainings were scored according to the area percentage of strong versican signal of total peri- and intratumoural stroma as low (<15%) or high (>or=15%). Epithelial staining of the tumours was scored as positive or negative. Low and high area percentage of strong stromal versican staining were observed in 133 and 166 carcinomas, respectively. A low area percentage of strong stromal versican staining correlated with mucinous histology (p = 0.019) and early International Federation of Gynecologists and Obstetritians (FIGO) stage (p < 0.0005), whereas a high percentage was associated with reduced 5-year survival rate of the patients (44% vs. 32%; p = 0.032). Versican was associated with the cancer cells in 151 tumours and correlated with clear cell histology (p < 0.0005), early FIGO stage (p = 0.049) and increased recurrence-free survival (63% vs. 47%; p = 0.032). However, in Cox's multivariate analyses with the conventional prognostic factors included, neither stromal nor cancer cell-associated versican reached a significant prognostic value. Versican is thus enriched in the malignant stroma surrounding and promoting the growth of ovarian cancer, probably acting with hyaluronan, and associates with unfavourable prognosis but does not constitute an independent indicator of patient survival.