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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.

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., (Copyright 2006 Wiley-Liss, Inc.)

Objective: To clarify the prognostic role of E-cadherin and beta- and gamma-catenins, and their relation to CD44 in epithelial ovarian carcinoma., Methods: The expression of E-cadherin and beta- and gamma-catenins was analysed immunohistochemically in 305 primary epithelial ovarian cancers and 44 metastases, and related to CD44 expression, clinicopathological factors, and the patients' survival., Results: Reduced cell surface expression of E-cadherin, beta-catenin, and gamma-catenin was particularly frequent in serous and endometrioid histological types. Reduced cell surface expression of E-cadherin and beta-catenin was also associated with poor differentiation. Nuclear positivity of beta-catenin was associated with high CD44 expression, endometrioid histology, and local stage of the tumour, whereas nuclear gamma-catenin expression was associated with serous histology and poor differentiation. In the univariate analysis, preserved cell surface beta-catenin expression in the whole study material and nuclear expression of beta- and gamma-catenins in the subgroup of endometrioid ovarian cancers were predictors of better 10 year disease related survival. Preserved cell surface expression of E-cadherin and beta-catenin predicted favourable recurrence-free survival. These statistical significances were not retained in multivariate analysis., Conclusions: The correlation between nuclear beta-catenin and CD44 indicates that beta-catenin may regulate the transcription of CD44 in epithelial ovarian cancer. E-cadherin-catenin complex members are associated with the prognosis of patients with epithelial ovarian cancer, but these univariate associations were not strong enough to compete for significance with the traditional clinicopathological factors.

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.

Several malignant tumors accumulate hyaluronan, a matrix component suggested to promote cancer cell migration and growth. To explore the potential clinical importance of this concept, we assessed the hyaluronan levels in epithelial ovarian cancer. A biotinylated affinity probe specific for hyaluronan was prepared and applied to histological sections of 309 epithelial ovarian cancers and 45 matched metastatic lesions. The staining was scored according to the percentage area of strong hyaluronan signal of total peri- and intratumoral stroma as low (<35%), moderate (35-75%), or high (>75%). Low, moderate, and high levels of stromal hyaluronan were observed in 95, 116, and 98 carcinomas, respectively. The high stromal hyaluronan level was significantly associated with poor differentiation, serous histological type, advanced stage, and large primary residual tumor, whereas it was not correlated with high CD44 expression on cancer cells. The 5-year outlook of the disease deteriorated with increasing stromal hyaluronan levels for both overall (45% versus 39% versus 26%; P = 0.002) and recurrence-free (66% versus 56% versus 40%; P = 0.008) survival. High levels of stromal hyaluronan were more frequent in metastatic lesions than in primary tumors (z = -3.9; P = 0.0001). In Cox's multivariate analyses, high level of stromal hyaluronan was an independent prognostic factor in all patients, as well as in stage-specific subgroups. These results suggest that stromal hyaluronan accumulation may be a powerful enhancer of tumor progression and, as such, provides a novel, independent prognostic marker and a potential target of therapy.

It is not known whether asthma constitutes a risk factor for osteoporosis or what the impact is of inhaled corticosteroids on bone mineral density (BMD). The study population (n = 3,222) was a random stratified sample from the Kuopio Osteoporosis Study, which included all women 47 to 56 yr of age residing in Kuopio Province, Eastern Finland. Spinal and femoral BMDs were measured using dual-energy X-ray absorptiometry. The BMD values of 119 asthmatics were cross-sectionally compared with those of 3,103 nonasthmatics. Of the 119 asthmatic women, 28 had not used corticosteroids, 65 had used oral corticosteroids, and 26 had used only inhaled corticosteroids. The asthmatics with no hormone replacement therapy (HRT) (n = 83) had lower mean spinal and femoral BMD value than did the corresponding nonasthmatics (spinal BMD, 1.083 +/- 0.150 [SD] versus 1.128 +/- 0.160 g/cm2, p < 0.05; femoral BMD, 0.894 +/- 0.112 [SD] versus 0.929 +/- 0.128 g/cm2, p < 0.05). Although BMDs were not significantly decreased in the asthmatics who had used inhaled corticosteroids, the duration of use correlated negatively with spinal BMD and was also associated with spinal BMD in multiple regression analysis. In perimenopausal women, asthma is associated with decreased bone density. This may be due to the corticosteroids rather than to the disease itself. However, HRT appears to be protective against bone loss also in asthmatics.

The prognostic significance of p53 expression in 316 archival epithelial ovarian cancers was assessed using a static, computer-aided image analysis system (CAS 200). Using a 10% cut-off point, 26% of primary tumors and 35% of their metastases were positive for p53 protein. p53 positivity closely correlated with tumor grade (p < 0.001), stage (p < 0.001), residual tumor (p < 0.001), serous histologic type (p = 0.005), and tumor recurrence (p = 0.007). The overall 5-year survival was 37%. In univariate survival analysis, high grade, advanced stage, older age at diagnosis, and residual tumor > 2 cm were significant predictors of poor overall survival. In both the overall (p < 0.001) and recurrence-free (p < 0.001) survival, p53 immunopositivity predicted poor prognosis. p53 expression was a significant prognostic factor of multivariate recurrence-free survival (RR 1.93, p = 0.03), but not of overall multivariate survival. In addition, p53 positivity was a marker of poor overall survival in patients with well or moderately differentiated tumors, early stage tumors, or residual tumor. Quantitation of p53 immunoexpression by CAS may offer an objective means to identify patients who need more aggressive adjuvant therapy or new treatment strategies.

Objective: The purpose of this study was to determine the potential of exposure of an infant to cervical human papillomavirus infection of the mother., Study Design: Cervical scrapes of the mothers and nasopharyngeal aspirate fluids of their infants were analyzed at the time of delivery. The study included 106 infants born by vaginal delivery or by cesarean section and their 105 mothers. Positive results were confirmed and typed by direct deoxyribonucleic acid sequencing or single-strand conformation polymorphism of the polymerase chain reaction product., Results: Both the mother's and her infant's samples were positive for the same type of human papillomavirus in 29 mother-infant pairs. Interestingly, five infants born by cesarean section were found to be human papillomavirus deoxyribonucleic acid positive for the same human papillomavirus type as their mother. The overall concordance between human papillomavirus types in the mother and her newborn was 69% (29/42). Regardless of match in types found in the mother's and her infant's sample, human papillomavirus deoxyribonucleic acid positivity was found in 39 of all the 106 infants (37%)., Conclusions: Our results indicate that the infant of the human papillomavirus-infected mother is exposed to infection even when the cervical infection of the mother is subclinical. The possibility of transplacental exposure has to be considered as well.

Changes in the management of 1120 twin pregnancies delivered in Tampere University Central Hospital during the years 1964-1985 were studied, together with changes in the pattern of perinatal deaths. Perinatal mortality decreased from 7.4% in 1964-68 to 3.5% in 1981-85. There were no significant changes in stillbirths. The decrease of perinatal mortality resulted from a reduction in early neonatal deaths, mainly those due to respiratory distress syndrome. Changes in obstetric management include earlier diagnosis by ultrasound, intrapartum monitoring, and an increase in cesarean section rate from 4% to 32%. There is still a need for a reduction in the number of very early preterm births, and for more effective intrauterine supervision of twin pregnancies.

The course and outcome of 23 monoamniotic (MA) twin pregnancies, delivered in Tampere University Central Hospital during the years 1964-1984, were studied retrospectively and compared to 1056 diamniotic (DA) twin pregnancies. The frequency of MA twins was 2.1% of twin pregnancies. Polyhydramnion complicated the pregnancy in 26% of MA vs 6% of DA pregnancies. Two cases were defined as acute polyhydramnion. Preterm labour was stated in 70% of MA pregnancies and deliveries before the 34th week were 4 times more common in MA than DA pregnancies. The cesarean section rate was more than double in MA pregnancies (39%). Entanglement of the umbilical cords was noted four times, and prolapse of the cord in three vaginally delivered cases. Perinatal mortality was 28% in MA vs 5% in DA twins. The most common causes of death were respiratory distress syndrome, congenital malformation and feto-fetal transfusion.

The aim of this prospective study was to determine the effect of hypertension in pregnancy (PH) on fetal and neonatal condition via other mechanisms than retarded intrauterine growth and preterm delivery. Sixty-six preterm and 175 full-term babies born to PH mothers were compared, respectively, with 183 preterm and 220 full-term babies born to non-hypertensive (non-PH) mothers over a 22-month period in 1984-1986. Small-for-gestational-age (SGA) children were examined separately from appropriate-for-gestational-age (AGA) children. Percentages of preterm babies and of both preterm and full-term SGA babies born to hypertensive mothers were twice as great as the percentages of such babies born to non-hypertensive mothers. Hypertension in pregnancy directly increased neonatal morbidity, but the effect was minor. In preterm babies it was related to intrauterine growth retardation and to pre-eclampsia. In full-term babies the effect was unrelated to the severity of hypertension.