The impact of lymph node density on survival of cervical cancer patients.

BACKGROUND: To evaluate the prognostic value of lymph node density (LND) in patients with lymph node-positive cervical cancer. METHODS: A total of 88 consecutive patients were included in our study. Patients were treated with cisplatin-based concomitant chemoradiotherapy after surgical staging was performed at the Medical University of Vienna. Lymph node density, that is, the ratio of positive lymph nodes to the total number of lymph nodes removed, was assessed pathologically. Patients were stratified into two groups according to LND: patients with LND 10%. Lymph node density was correlated with clinicopathological parameters by chi(2)-tests. Univariate log-rank tests and multivariate Cox regression models were used to evaluate the association between LND and survival. RESULTS: A significant correlation between LND and FIGO stage (P=0.03), but not patients' age (P=0.2), histological grade (P=0.8), and histological type (P=0.5), was observed. In a univariate survival analysis, LND (P=0.01; P=0.01), FIGO stage (P=0.01; P=0.008), and histological grade (P=0.03; P=0.04) were associated with disease-free and overall survival, respectively. Patients with LND >10% had impaired disease-free and overall survival rates compared with patients with LND 10% is associated with an impaired disease-free and overall survival. Lymph node density may be used as an independent prognostic parameter in patients with lymph node-positive cervical cancer.

The prognostic value of plasma fibrinogen levels in patients with endometrial cancer: a multi-centre trial.

BACKGROUND: To analyse the correlation between pre-treatment plasma fibrinogen levels and clinical-pathological parameters in patients with endometrial cancer and to assess the value of plasma fibrinogen as a prognostic parameter. METHODS: Within a retrospective multi-centre study, the records of 436 patients with endometrial cancer were reviewed and pre-treatment plasma fibrinogen levels were correlated with clinical-pathological parameters and patients' survival. RESULTS: The mean (s.d.) pre-treatment plasma fibrinogen level was 388.9 (102.4) mg per 100 ml. Higher plasma fibrinogen levels were associated with advanced tumour stage (FIGO I vs II vs III and IV, P=0.002), unfavourable histological subtype (endometrioid vs non-endometrioid histology, P=0.03), and higher patients' age (< or =67 years vs >67 years, P=0.04), but not with higher histological grade (G1 vs G2 vs G3, P=0.2). In a multivariate analysis, tumour stage (P<0.001 and P<0.001), histological grade (P=0.009 and P=0.002), patients' age (P=0.001 and P<0.001), and pre-treatment plasma fibrinogen levels (P=0.04 and P=0.02) were associated with disease-free and overall survival, respectively. CONCLUSION: Plasma fibrinogen levels can be used as an independent prognostic parameter for the disease-free and overall survival of patients with endometrial cancer.

Serum concentrations of vascular endothelial growth factor in vulvar cancer.

The aim of the present study was to evaluate serum concentrations of vascular endothelial growth factor (VEGF) in patients with vulvar cancer and healthy female controls with respect to correlation of VEGF with clinicopathological parameters and impact on the patients' prognosis. Serum concentrations of VEGF were measured using a commercially available ELISA. Results were correlated to clinical data. Median serum concentrations of VEGF in patients with vulvar cancer (n = 41) and healthy female controls (n = 130) were 260 (range, 33-1216) pg/ml and 216 (range, 0-777) pg/ml, respectively (Mann-Whitney U test, P = 0.048). Serum concentrations of VEGF significantly correlated with tumor stage (Mann-Whitney U test, P = 0.02) but not with histological grade (Mann-Whitney U test, P = 0.2). In a univariate analysis, elevated pretreatment serum concentrations of VEGF were significantly correlated with a shortened disease-free and overall survival (Wilcoxon test, P = 0.03; and Wilcoxon test, P = 0.04, respectively). A multivariate Cox regression model considering tumor stage and serum concentrations of VEGF revealed, however, that serum concentrations of VEGF did not confer additional prognostic information to that already obtained by the established prognosticator tumor stage (multivariate Cox regression model: P = 0.9 and P = 0.8, respectively). Our data indicate that angiogenesis, as reflected by serum concentrations of VEGF, plays a functional role in vulvar carcinogenesis. VEGF seems to be a mediator of vulvar tumor growth but not of tumor cell dedifferentiation. Although associated with impaired disease-free and overall survival, pretreatment serum concentrations of VEGF are not an independent predictor of outcome in patients with vulvar cancer.

Clinical value of postnatal autopsy and genetics consultation in fetal death.

The aim of the present study was to investigate the clinical use of postnatal autopsy and genetics consultation in cases of fetal death in a teaching hospital. A retrospective analysis of medical records including pathology and genetics reports was performed in all cases of fetal death in which a woman delivered at Ben Taub General Hospital, Houston, Texas over a 2-year period. Cases were excluded when gestational age of the fetus was less than 20 weeks. Fetuses were only included when the 1- and 5-min Apgar scores were 0 and 0, respectively. There were 139 fetal deaths and 12,209 live born infants during the study period (stillbirth rate 1.125%). Although pathology services were used in 96.2%, a genetics consultation was obtained in only 12% of cases. Fetal autopsy provided a certain cause of fetal death in 19.4%, a probable cause for death in 36.3%, and was inconclusive in 44.3%. Among the cases in which a genetics consultation was obtained, a certain and probable cause for fetal death was found in 20% and 20% of cases, respectively. The utilization of genetics consultation was found to be independent of multiple clinical variables examined including ultrasound data, identification of maceration, and training level of resident. Our data show a frequent use of pathologic examination in cases of fetal death and an infrequent use of genetics consultation services. The request for genetics consultation seemed to have been made at random.

Polymorphisms within the interleukin-1 beta gene cluster and preeclampsia.

OBJECTIVE: To identify associations between polymorphisms within the interleukin-1 beta gene cluster, all of which increase protein expression, and preeclampsia. METHODS: We genotyped a Hispanic population (69 women with preeclampsia and 47 controls) for two polymorphisms of the interleukin-1 beta gene (promoter region and exon 5) and one polymorphism of the interleukin-1 receptor antagonist gene in intron 2. Clinical data were collected from medical records. Values are given as means or medians. Statistical power to identify a difference in occurrence of interleukin-1 beta promoter, interleukin-1 beta exon 5, and interleukin-1 receptor antagonist gene polymorphisms in women with preeclampsia compared with controls was 21%, 15.9%, and 30.9%, respectively. RESULTS: We found no association between any single polymorphism and occurrence of preeclampsia. Among women with preeclampsia, those with polymorphism of interleukin-1 receptor antagonist gene had higher mean systolic blood pressure (BP) at admission (178 +/- 33.4 versus 159 +/- 19.5 mmHg, P =.039). When all three polymorphisms combined were evaluated, women with preeclampsia and at least three mutant alleles (n = 8) had higher mean systolic BP at admission (182 +/- 30 versus 160 +/- 20.5 mmHg, P =.009) and increased alanine aminotransferase (67 [10--1024] versus 20 [3--407] IU/L, P =.04) and aspartate aminotransferase (119 [25--2239] versus 24 [4--489] IU/L, P =.002). At admission, BP in controls was independent of any polymorphism identified. CONCLUSION: Although the power of this study was limited, our data do not support a role for polymorphisms of the interleukin-1 beta and interleukin-1 receptor antagonist genes in the pathogenesis of preeclampsia among Hispanic women. Our findings do suggest that polymorphisms within the gene cluster might influence severity of preeclampsia.

Vascular endothelial growth factor serum concentrations in ovarian cancer.

OBJECTIVE: To determine whether serum vascular endothelial growth factor is an independent prognostic factor in ovarian cancer patients. METHODS: We measured vascular endothelial growth factor in pretreatment serum samples of 60 women with International Federation of Gynecology and Obstetrics stages I to IV epithelial ovarian cancer, using an enzyme-linked immunosorbent assay. The results were correlated to clinical data. RESULTS: The median vascular endothelial growth factor serum level in ovarian cancer patients was 466.1 pg/mL (range 69.7-2835 pg/mL). The 75% quartile was defined as a cut-off level. Elevated vascular endothelial growth factor serum levels before therapy correlated significantly with a poorer disease-free (log-rank-test, P = .003) and overall survival (log-rank-test, P = .007). Multivariate analysis revealed serum vascular endothelial growth factor to be an independent prognostic factor of overall and disease-free survival. When median pretreatment levels of vascular endothelial growth factor were grouped by tumor stage, histologic grade of tumor cells, histologic type of the tumor, lymph node involvement, age of patient, and residual tumor mass, we found a statistically significant correlation between serum levels of vascular endothelial growth factor and histologic grade (Mann-Whitney U test, P = .03). CONCLUSION: Vascular endothelial growth factor appears to be an additional factor for predicting the outcome of patients with epithelial ovarian cancer. Owing to its independence from established prognostic factors, vascular endothelial growth factor could be used for prognostic information in clinically relevant subsets such as early-stage or lymph node-negative ovarian cancers.

Influence of acupuncture on maternal serum levels of interleukin-8, prostaglandin F2alpha, and beta-endorphin: a matched pair study.

OBJECTIVE: To measure the serum levels of interleukin (IL)-8, prostaglandin (PG) F2alpha, and beta-endorphin in parturients with acupuncture treatment and in controls to clarify the effect of acupuncture and duration of labor on the serum levels of substances active in cervical ripening and dilatation. METHODS: A matched pair study was performed involving 80 women with and without prenatal acupuncture treatment, matched for age and parity. Serum levels of IL-8, PGF2alpha, and beta-endorphin were measured in serum samples taken after delivery by use of enzyme-linked immunosorbent assay, enzyme immunoassay, and immunoradiometric assay, respectively. RESULTS: The mean difference in total duration of labor between matched pairs with and without acupuncture was -136.5 minutes (95% confidence interval [CI] 191.1 minutes, -81.9 minutes; paired t test, P < .001). The mean difference of the duration of the first and second stages of labor between matched pairs with and without acupuncture was -138.8 minutes (95% CI 188.6, -89.0 minutes; paired t test, P < .001) and 2.3 minutes (95% CI 15.5, 20.1 minutes; paired t test, P = .8), respectively. The geometric means of ratios of IL-8, PGF2alpha, and beta-endorphin between matched pairs in women with and without acupuncture showed no statistically significant differences. Serum levels of IL-8, PGF2alpha, and beta-endorphin were not significantly correlated with the duration of the first and second stages of labor. CONCLUSION: Prenatal acupuncture treatment significantly reduces the duration of labor and may be a valuable tool in prenatal preparation. Serum levels of IL-8, PGF2alpha, and beta-endorphin are not significantly influenced by acupuncture and are therefore not likely to mediate acupuncture-related effects during labor.

Serum soluble Fas levels in ovarian cancer.

OBJECTIVE: To determine the value of serum soluble Fas levels as a prognostic marker for survival of women with ovarian cancer and as a discriminator between benign and malignant adnexal masses. METHODS: Serum soluble Fas levels were measured with an enzyme-linked immunosorbent assay in 52 women with ovarian cancer, 30 women with benign ovarian cysts, and 35 healthy women. RESULTS: Median serum soluble Fas levels in women with ovarian cancer, women with benign ovarian cysts, and healthy women were 3.7 (range 1.6-14.5), 2.3 (range 1.3-4.1), and 1.5 ng/mL (range 0.1-5.6), respectively (P <. 001). A univariate logistic regression model showed a significant influence of serum soluble Fas and CA 125 levels on the odds of presenting with ovarian cancer versus benign cysts (P <.001 and P =. 001, respectively). In a multivariable logistic regression model for soluble Fas and CA 125, both markers showed a statistically significant influence on the odds of presenting with ovarian cancer versus benign cysts (P =.01 and P =.01, respectively). Increased pretreatment serum soluble Fas levels were associated with shortened disease-free and overall survival (P =.002 and P =.001, respectively). A multivariable Cox regression model identified serum soluble Fas levels as a significant prognostic factor for disease-free and overall survival, independent of tumor stage (P =. 04 and P =.03, respectively). CONCLUSION: Soluble Fas levels might be useful as a discriminator between benign ovarian cysts and ovarian cancer, adding to the information obtained with the use of the established tumor marker CA 125. Pretreatment serum soluble Fas levels also might be an independent prognostic factor for disease-free and overall survival.

Prognostic significance of tumor angiogenesis in endometrial cancer.

OBJECTIVE: To determine the prognostic effect of intratumor microvessel density in a series of unselected patients with endometrial carcinoma. METHODS: We reviewed 93 consecutive patients treated surgically for endometrial cancer at the University Hospital of Vienna between 1983 and 1989. Histologic sections were obtained from original paraffin-embedded blocks and stained immunohistochemically for CD34 antigen. Microvessel density was determined by enumeration of intratumor CD34-positive cells under a light microscope at 200 x magnification using an examination area of 0.74 mm2. Log-rank test and Cox proportional-hazards models (univariate and multivariate) were applied for overall survival analysis. RESULTS: Overall, the 25% quantile of survival was reached at 37.9 months. The 5-year survival rate was 82.2% in 69 patients whose tumors had microvessel counts no more than 100/0.74 mm2 field, and 52.0% in 24 patients whose tumors had microvessel counts of more than 100/0.74 mm2 field (log-rank P = .004). In the multiple Cox model, high microvessel counts (relative risk [RR] 1.2; 95% confidence interval [CI] 1.1, 1.4) as well as undifferentiated tumors (RR 6.1; CI 2.2, 16.8), and advanced stage of disease (RR 2.6; CI 1.3, 5.1) independently exerted an adverse influence on the survival of patients with endometrial cancer. CONCLUSION: High intratumor microvessel count is associated with poor survival of patients with endometrial cancer.

Value of urethral pressure profilometry in the female incontinent patient: a prospective trial with an 8-channel urethral catheter.

OBJECTIVES: To measure the pressure profiles at different positions of the urethral circumference simultaneously. METHODS: Twenty-two women with symptoms of genuine stress incontinence underwent urogynecologic assessment and multichannel urethral pressure profilometry (UPP) at rest with a specially designed 8-channel urethral catheter with radial openings. RESULTS: The distribution pattern of maximum urethral closure pressure (MUCP) and functional urethral length (FUL) values were significantly different (P=0.004 and P=0.0004, respectively). Most of the highest MUCP values per patient were found between channels 2 and 4 (P=0.015); most of the greatest FUL values per patient were found between channels 3 and 4 (P=0.15). CONCLUSIONS: The data of our study substantiate asymmetric radial pressure distribution within the urethra and underline the necessity of cautious interpretation of results of conventional single-channel UPP, which might vary because of transducer orientation.

Influence of the angiotensinogen gene on the ovulatory capacity of mice.

OBJECTIVE: The tissue-bound ovarian renin-angiotensin system (OVRAS) is critically involved in ovulation in humans and rodents. Mice with disruption and overexpression of the angiotensinogen gene (Agt) have been previously generated. We investigated the influence of varying Agt gene expression on the ovulatory capacity and early embryonic development in mice. DESIGN: Observational study of genetically altered mice and their response to a superovulation protocol. SETTING: Academic research institution. ANIMAL(S): Mice with varying copy numbers of Agt (one copy: n = 48; two copies: n = 51; three copies: n = 20; four copies: n = 24). INTERVENTION(S): Superovulation protocol, oocyte culture. MAIN OUTCOME MEASURE(S): Number of oocytes harvested, early embryonic development of zygotes, evaluation of ovarian histology, serum estradiol measurements. RESULT(S): The mean number of oocytes harvested was greatest in wild-type mice (two copies of Agt, 39.9 +/- 14) with a reduction of ovulatory capacity in mice overexpressing Agt (three copies [34.8 +/- 11.7] and four copies [31.2 +/- 12.4], P =.026). Mice with one copy of Agt showed a slight decrease of ovulatory capacity compared to wild-type mice (35.8 +/- 15.2, P =.29). Ovarian histology, serum estradiol levels, and early embryonic development were independent of the Agt genotype. CONCLUSION(S): Overexpression of Agt was associated with reduced ovulatory capacity, but with none of the other parameters that were evaluated. These findings support an important role of the ovarian renin-angiotensin system in the process of follicular rupture.

A polymorphism of the interleukin-1beta gene and idiopathic recurrent miscarriage.

OBJECTIVE: Proinflammatory cytokines have been described to be involved in the pathogenesis of idiopathic recurrent miscarriage (IRM). We investigated the association between IRM and a polymorphism in exon 5 of the interleukin-1beta gene (IL1B) and interleukin-1beta (IL-1beta) serum levels. DESIGN: Case control study. SETTING: Academic research institution. SUBJECTS: One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 68 healthy controls with at least two live births and no history of pregnancy loss. INTERVENTIONS: Peripheral venous puncture. MAIN OUTCOME MEASURES: An IL1B exon 5 (position +3953) gene polymorphism was analyzed by PCR amplification followed by restriction fragment length polymorphism analysis. IL-1beta serum levels were analyzed by a commercially available ELISA. RESULTS: Allele frequencies in women with IRM and controls were 77.9% and 80.8%, respectively, for the E1 allele (wild type), and 22.1% and 19.2%, respectively, for the E2 allele (mutant). No association between the E2 allele and the occurrence of IRM was found (P=.57, odds ratio =.83). Genotype frequencies and IL-1beta serum levels were not significantly different between the study group and the control group. CONCLUSIONS: This is the first report on an IL1B polymorphism in IRM. Although known to alter IL-1beta expression, the investigated IL1B polymorphism is not associated with IRM and increased serum levels in a large Caucasian population.

The PROGINS progesterone receptor gene polymorphism and idiopathic recurrent miscarriage.

OBJECTIVE: Progesterone inhibits lymphocyte cytotoxicity, natural killer cell degranulation, and release of proinflammatory cytokines and has been shown to protect against spontaneous miscarriage. We investigated the association between idiopathic recurrent miscarriage (IRM) and the PROGINS 306 base pair insertion polymorphism in intron G of the progesterone receptor gene, which is known to segregate with progesterone-dependent neoplasms. METHODS: In a case-control study we investigated 125 women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 79 healthy controls with at least two live births and no history of pregnancy loss. Peripheral venous puncture, DNA extraction, and polymerase chain reaction were used to genotype women for the presence of the PROGINS polymorphism. RESULTS: Allele frequencies among women with IRM and controls were 85.2% and 89.2%, respectively, for allele T1 (wild type) and 14.8% and 10.8%, respectively, for allele T2 (mutant). No association between allele T2 and the occurrence of IRM was found (P =.3; odds ratio [OR] 0.69; confidence interval [CI] 0.34, 1.40). Genotype frequencies were not significantly different between the study group (T1/T1 73.6%, T1/T2 23.2%, T2/T2 3.2%) and the control group (T1/T1 79.7%, T1/T2 19%, T2/T2 1.3%) (P =.4). Between women with primary and secondary IRM, there were no statistically significant differences with respect to allele frequencies (82% versus 87%, P =.4 for allele T1 and 12% versus 13%, P =.6 for allele T2). CONCLUSIONS: We found that the PROGINS polymorphism in the progesterone receptor gene was not associated with IRM in white women.

Maternal basic fibroblast growth factor serum levels are associated with pregnancy-induced hypertension.

OBJECTIVE: To test the hypothesis that serum levels of basic fibroblast growth factor (bFGF) are altered among women with pregnancy-induced hypertension (PIH) and are associated with disease severity. METHODS: We evaluated serum levels of bFGF in 46 women with PIH, 46 age- and parity-matched healthy pregnant women, and 46 healthy nonpregnant controls. Enzyme-linked immunosorbent assays were used to determine serum levels of bFGF. Results were correlated to clinical data. RESULTS: The overall mean serum levels of bFGF were 3.2 (standard deviation [SD] 9.3) micromol/L. Mean serum levels of bFGF in normal controls, healthy pregnant women, and women with PIH were 0 (SD 0) micromol/L, 2.6 (SD 6.3) micromol/L, and 6.8 (SD 13.8) micromol/L, respectively (P =.003) for normal controls compared with healthy pregnant women and P <.001 for healthy pregnant women compared with women with PIH). In a univariate logistic regression model bFGF showed a significant influence on the odds of presenting with PIH compared with healthy pregnant women (P =.002). The mean serum levels of bFGF in women with severe PIH and in women with mild PIH were 4.4 (SD 10.6) micromol/L and 9.5 (SD 17.3) micromol/L, respectively (P =.1). In a univariate logistic regression model bFGF did not reveal a significant influence on the odds of developing severe PIH (P =.3). CONCLUSIONS: Elevated serum levels of bFGF are associated with PIH, but bFGF does not seem to be a useful prognostic parameter for severe PIH.

Placental expression and serum levels of cytokeratin-18 are increased in women with preeclampsia.

OBJECTIVE: To evaluate placental expression and serum cytokeratin-18 in women with preeclampsia. METHODS: Serum cytokeratin-18 was evaluated in 44 women with preeclampsia and 44 healthy pregnant women using an immunoradiometric assay. Placental expression of cytokeratin-18 was investigated in specimens from 23 women with preeclampsia and 20 healthy pregnant women by immunohistochemistry. RESULTS: Median serum cytokeratin-18 in women with preeclampsia and healthy pregnant women was 106.7 and 76.0 U/L, respectively (P =.02). Among women with preeclampsia, serum cytokeratin-18 was significantly associated with severity of disease (P =.001) and showed a sensitivity (standard error) and specificity (standard error) of 85% (7%) and 65% (12%), respectively. In placental specimens, the cytoplasm of the syncytiotrophoblast stained positive for cytokeratin-18 with strong and widespread staining in 83% and 45% of placental specimens of women with preeclampsia and healthy pregnant women, respectively (P =.01). CONCLUSION: Elevated serum cytokeratin-18 values are associated with disease severity in women with preeclampsia. Our data provide additional evidence that the placenta might be the source of the elevated serum cytokeratin-18 values in women with preeclampsia.

Serum levels of angiogenin (ANG) in invasive cervical cancer and in cervical intraepithelial neoplasia (CIN).

BACKGROUND: The propensity of malignant tumors to increase in size, to invade locally and to metastasize is dependent on angiogenesis, which is induced by a variety of proteins including the family of fibroblast growth factors, vascular endothelial growth factor and angiogenin (ANG). The aim of the present study was to measure the serum levels of ANG in patients with CIN and invasive cervical cancer and to evaluate a possible correlation between ANG and various clinicopathologic parameters. MATERIALS AND METHODS: Blood was collected from 62 patients with invasive cervical cancer and 47 patients with CIN. Serum samples of 30 age-matched healthy women acting as a control group were obtained. Determination of serum levels of ANG was performed using a quantitative human ANG immunoassay. RESULTS: The overall median ANG serum level was 272.0 pg/ml (range 101.6-869.2). The median serum levels of ANG were 248.9 (range 101.6-307.2) for healthy female controls, 246.8 (range 169.7-468.1) for patients with CIN and 308.1 pg/ml (range 180.1-869.2) for patients with invasive cervical cancer. Serum levels of ANG were significantly elevated in patients with invasive cervical cancer compared with patients with CIN (p < 0.05) as well as healthy female controls (p < 0.05). No difference was found between ANG serum levels in women with CIN, and healthy controls (p < 0.05). No correlations were found between serum levels of ANG and clinico-pathologic parameters (p > 0.05). CONCLUSIONS: Our data indicate the important role of ANG in tumor angiogenesis in invasive cervical cancer as ANG serum levels were significantly elevated in these patients. However, elevated ANG serum levels seem to occur only after the transformation from pre-invasive to invasive lesions.

Prognostic value of beta1-integrin (=CD29) in serous adenocarcinomas of the ovary.

BACKGROUND: Integrins are heterodimeric transmembranous proteins, comprised of two transmembrane subunits, called alpha and beta. They bind to various structures of the extra cellular matrix (ECM) and are responsible for cell-cell interactions. The aim of the current study was to evaluate the prognostic value of beta1-integrin in patients suffering from malignant serous surface epithelial-stromal tumors of the ovary. MATERIALS AND METHODS: With immunohistochemical methods we investigated 76 formalin-fixed, paraffin-embedded tissue samples. FIGO stages I, II, III and IV were present in 18, 10, 41 and 7 cases, respectively. RESULTS: 12 sections (15.8%) stained positive for beta1-integrin (=CD29), 64 sections (84.2%) showed no expression of beta1-integrin. The product limit method by Kaplan and Meier showed no statistical significance of beta1-integrin expression on overall survival, (p = 0.1005, log-rank test). Also the univariate Cox regression analysis showed no statistical significance of beta1-integrin expression on overall survival (p=0.1066), whereas in the multivariate analysis, adjusted for grading, FIGO stage and residual tumor, the expression of beta1-integrin turned out to be significantly correlated with reduced overall survival (p=0.0208). CONCLUSION: Our results using multivariate Cox regression analysis indicated a shorter overall survival for patients with positive staining for beta1-integrin in malignant serous surface epithelial-stromal tumors of the ovary. This pilot study warrants further investigation of the role of beta1-integrin in ovarian cancer.

Immunohistochemical detection of matrix metalloproteinases (MMP) 1 and 2, and tissue inhibitor of metalloproteinase 2 (TIMP 2) in stage I and II endometrial cancer.

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of zinc-dependent metalloendopeptidases which participate in the degradation of collagen and other extracellular matrix macromolecules. Expression of gelatonic MMPs, such as MMP-2 has been linked to enhanced tumor invasion and metastasis in in vitro and in vivo model systems. It was the aim of this study to determine whether the expression of MMP-1, MMP-2, and TIMP-2 correlates with survival in patients with surgically treated endometrial cancer. METHOD: A sample of 103 paraffin-embedded tumor specimens of surgical treated endometrial cancer was immunohistochemically investigated. RESULTS: MMP-1, MMP-2, and TIMP-2 were detected by immunohistochemistry in 95% (98/103), 87% (89/103), and 80% (82/103) of the tumour samples, respectively. Correlation coefficients for MMP-1/MMP-2, MMP-1/TIMP-2, MMP-2/TIMP-2 were 0.28 (p = 0.004), 0.05 (p = 0.6), and -0.03 (p = 0.73), respectively. In the univariate analysis, the expression of MMP-1 (log-rank test, p = ns), MMP-2 (log-rank test, p = ns), and TIMP-2 (log-rank test, p = ns) were not associated with overall survival. CONCLUSION: MMP-1, MMP-2, and TIMP-2, detected by immunohistochemistry are not helpful in predicting the prognosis of endometrial cancer patients.

Humoral p53 antibody response is a prognostic parameter in ovarian cancer.

BACKGROUND: Mutant p53 protein may become the target of a tumor-specific humoral and cellular immune response. MATERIAL AND METHODS: We used a specific qualitative p53 antibody ELISA to investigate serum samples of 33 patients with ovarian cancer taken prior to therapy. Additionally, we sought to evaluate whether p53 antibodies are also present in the sera of 17 patients with benign ovarian tumors. RESULTS: p53 antibodies were detected in 36% of serum samples. There was a statistically significant association between p53 serum antibody response and poor overall survival (p < 0.006). No significant associations were found between p53 antibody status and histological type, histological grade, and tumor stage. In 81% of serum samples, no changes from p53 antibody negativity to positivity or vice versa during follow-up were observed. p53 antibodies were also detected in the sera of 18% of patients with benign ovarian tumors. CONCLUSIONS: The results of this preliminary study suggest that a p53 antibody response in patients with ovarian cancer is associated with poor prognosis. A qualitative method of p53 antibody detection cannot be used to monitor the clinical course of ovarian cancer.

Immunohistochemical detection of matrix metalloproteinases (MMP) 1 and 2, and tissue inhibitor of metalloproteinase 2 (TIMP 2) in stage IB cervical cancer.

OBJECTIVE: Matrix metalloproteinases (MMPs) are a family of zinc-dependent metalloendopeptidases which participate in the degradation of collagen and other extracellular matrix macromolecules. Expression of gelatonic MMPs, such as MMP-2 has been linked to enhanced tumor invasion and metastases in in vitro and in vivo model systems. It was the aim of this study to determine whether the expression of MMP-1, MMP-2, and TIMP-2 correlates with survival in patients with surgically treated cervical cancer stage IB. METHODS: A sample of 154 paraffin-embedded tumor specimens of surgical treated FIGO stage IB cervical cancer was immunohistochemically investigated. RESULTS: MMP-1, MMP-2, and TIMP-2 were detected by immunohistochemistry in 74% (113/154), 32% (49/154), and 80% (107/154) of the tumor samples, respectively. Correlation coefficients for MMP-1/MMP-2, MMP-1/TIMP-2, MMP-2/TIMP-2 were 0.14 (p = 0.12), 0.37 (p = 0.0001), and 0.17 (p: 0.005), respectively. A significant correlation was found between MMP-1 and lymph node status (P < 0.01) and lymphvascular space invasion (P < 0.05). The expression of MMP-1 (log-rank test, p = 0.6), MMP-2 (log-rank test, p = 0.8), and TIMP-2 (log-rank test, p = 0.15) were not correlated with overall survival. CONCLUSION: MMP-1, detected by immunohistochemistry, seems to play a role in the development of lymphvascular space invasion and lymph node metastases, but is not helpful in predicting the prognosis of cervical cancer patients.