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M Massobrio

Publications and source records attributed to M Massobrio.

At least 19 recordsLinked to original sources
PubMed2006

Should we consider gestational diabetes a vascular risk factor?

Few and contrasting data have reported vascular endothelial dysfunction and increased serum levels of endothelial dysfunction and inflammatory markers in women with previous gestational diabetes mellitus (pGDM). We aimed at evaluating 6.5 years after delivery: intimal medial thickness (IMT), and C-reactive protein (CRP), interleukin-6 (IL-6), E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) levels in 82 non-pregnant pGDM and 113 control women without pGDM. A subgroup of 21 women, taken from the pGDM group, showing current normal BMI, and no metabolic abnormalities, was separately analysed. All the subjects were free of medication and non-smokers. Women with pGDM, independently by their current BMI and presence of metabolic abnormalities, showed significantly higher E-selectin, ICAM-1 and IMT values than controls. IMT proved to be significantly associated with pGDM in a regression model, after adjustments for BMI, waist circumference, blood pressure, and glucose values (beta=0.046; 95% CI 0.028-0.064). In all pGDM women, E-selectin, ICAM-1, IL-6 and hs-CRP values were significantly associated with IMT in the same model. Post-GDM women, despite being currently free from metabolic abnormalities, showed higher values of markers of endothelial dysfunction and IMT than controls, consistent with an increased future cardiovascular risk.

Adult↗
PubMed2006

The use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study.

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were <1200 pg/ml. The primary outcome measure was the number of follicles >or=16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation.

Anovulation↗
PubMed2006

Fertility in patients with multiple sclerosis: current knowledge and future perspectives.

The issue of fertility in patients with multiple sclerosis (MS) has not been exhaustively studied. Epidemiological data have suggested that spontaneous fecundity might be reduced; several endocrine and sexual disturbances potentially interfering with reproduction have been evidenced in MS patients of both sexes. Moreover, some medical treatments used in MS (e. g., mitoxantrone, cyclophosphamide) may exert detrimental effects on spermatozoa as well as on oocytes, leading to early impairment of fertility. This review illustrates the factors potentially interfering with fertility in MS and discusses the therapeutic tools that may be used to promote fertility in these patients. The safety of hormonal therapies in MS is also examined. The current applications of assisted reproductive technology (ART) are discussed, including in vitro fertilisation (IVF) techniques. Currently available methods to preserve fertility in patients that undergo cytotoxic treatments by means of sperm/oocyte cryostorage or by ovarian fragment cryopreservation and autografting are considered.

Antineoplastic Agents↗
PubMed2006

[Leptin as a possible marker of augmented metabolic risk during pregnancy].

AIM: Leptin is a proteic hormone, isolated in 1994, mainly synthetized in the white adipose tissue. Aim of this study was to compare leptin concentrations in normal pregnancies with those measured in pregnancies complicated by gestational diabetes or gestational hypertension or pre-eclampsia. METHODS: We enrolled 48 pregnant women: 18 with uncomplicated pregnancy, 11 with gestational diabetes, 19 with gestational hypertension or pre-eclampsia. Leptin concentrations were measured in maternal serum at enrollment, together with insulin and cortisol, at delivery and in the immediate postpartum. At delivery serum leptin was calculated in the cord blood too. RESULTS: Fasting plasma leptin and insulin were higher in the group of patients with gestational hypertension, than in the other groups. Third-trimester maternal leptin concentrations correlated significantly with insulin levels in the group of women with gestational diabetes and in the group with gestational hypertension or pre-eclampsia, but not in the women with an uncomplicated pregnancy. CONCLUSIONS: Leptin concentrations in pregnancies complicated by hypertensive disorders are significantly higher than in normal pregnancies. The increased leptin concentrations are independent of associated proteinuria, as women with simple gestational hypertension and preeclampsia showed comparable third-trimester leptin concentrations. In both women with gestational diabetes and women with hypertensive disorders, serum leptin correlated closely with serum insulin, suggesting that the association between leptin and insulin resistance is preserved in pregnancy. Whatever the reasons for an increased maternal leptin production in pregnancies complicated by hypertension, maternal leptin homeostasis does not seem to influence foetal serum leptin concentrations, which seems to be mainly related to birth weight.

Adult↗
PubMed2005

Glutathione S-transferase polymorphisms and ovarian cancer treatment and survival.

OBJECTIVE: Members of the glutathione S-transferase (GST) family have been shown to have functional polymorphisms that may affect drug metabolism and influence the effects of chemotherapy and survival from cancer. GSTM1, GSTT1, and GSTP1 genotypes were evaluated for their role in ovarian cancer treatment and survival. METHODS: DNA was extracted from tumor tissues of 215 patients diagnosed with primary epithelial ovarian cancer. GSTM1 and GSTT1 genotypes were determined by multiplex PCR; GSTP1 genotypes were assessed with PCR-RFLP. Associations between GST polymorphisms and risk of ovarian cancer progression or death were analyzed using Cox proportional hazards regression; subgroups of patients receiving different chemotherapeutics were also evaluated. RESULTS: GST polymorphisms were not found to be associated with patient or tumor characteristics or response to treatment. However, GSTM1 null patients were less likely to have disease progression (HR: 0.65, 95% CI: 0.43-0.99) or to die (HR: 0.68, 95% CI: 0.45-1.03) compared to patients with GSTM1. Patients with GSTM1 null and GSTP1 ile/val or val/val (reduced function) had a further reduction in risk of disease progression compared to patients with GSTM1 or GSTP1 ile/ile (HR: 0.42, 95% CI: 0.24-0.75). A similar association was also suggested for overall survival (HR: 0.61, 95% CI: 0.36-1.05). Subgroup analyses indicated that the effects of GST on survival were more pronounced among patients treated with specific chemotherapeutics. CONCLUSION: These findings support the idea that reduced GST function may improve ovarian cancer survival after post-operative chemotherapy; evaluation of GST functional polymorphisms may help to predict ovarian cancer prognosis.

Adult↗
PubMed2005

Preserved insulin sensitivity and {beta}-cell activity, but decreased glucose effectiveness in normal-weight women with the polycystic ovary syndrome.

Insulin resistance and hyperinsulinemia are often considered intrinsic features of the polycystic ovary syndrome (PCOS). Nevertheless, conflicting results of insulin sensitivity and secretion have been obtained in the subgroup of normal-weight women with PCOS. Differences in body composition, ethnicity, and diet composition and a family history of metabolic diseases may act as confounding variables in women with PCOS. In the present study, insulin sensitivity and secretion were estimated by an iv glucose tolerance test (IVGTT), analyzed by minimal models, in 20 normal-weight healthy women with PCOS and no family history of type 2 diabetes mellitus and in 20 normally ovulating women, matched for age and body mass index. Insulin sensitivity [mean (95% confidence intervals); PCOS 4.0 (2.8-5.1) vs. controls 4.5 (3.5-5.4) 10(-4) min(-1)/microU.ml], and insulin secretion, expressed as the acute insulin response to glucose [PCOS 3.7 (3.3-4.2) vs. controls 3.7 (3.4-4.0) microU/ml] were similar in the two groups. The women with PCOS showed an increased proportion of total body fat (PCOS 29% vs. controls 27.2%; P < 0.01). They also showed decreased glucose effectiveness, i.e. the proportion of glucose uptake independent from insulin activity [PCOS 2.6 (2.1-3.0) vs. controls 3.8 (3.0-4.6) mg x 100 min(-1); P = 0.01]. The levels of insulin sensitivity and of glucose effectiveness did not correlate in either group. Whether the isolated finding of decreased glucose effectiveness could reflect an early stage in the development of the metabolic aberrations often associated with the syndrome remains to be clarified.

Adult↗
PubMed2005

C-reactive protein and tumor necrosis factor-alpha in gestational hyperglycemia.

OBJECTIVES AND STUDY DESIGN: Increasing evidences support an inflammatory origin for gestational hyperglycemia. This paper aims at investigating, cross-sectionally and prospectively, the relationships between tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) levels in normoglycemic and hyperglycemic pregnancies of women with and without conventional risk factors for gestational diabetes (GDM). RESULTS: Both at simple and multiple correlations TNF-alpha levels are associated to fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) values and gestational hyperglycemia, while high sensitivity CRP (hsCRP) levels to body mass index (BMI). Furthermore, the TNF-alpha levels of the second trimester and their increments in the third trimester are significant predictors of insulin levels measured at 32-36 weeks in the subgroup of hyperglycemic women with < or = 35 yr, BMI <25 kg/m2 and the absence of a first-degree relative with Type 2 diabetes (respectively, beta=1.1; 95%CI 0.66-1.48; p=0.002 and beta=1.0; 95%CI 0.36-1.66; p=0.02), in a multiple regression model, after multiple adjustments. In a second cohort of women at low risk for GDM (<25 yr, BMI <25 kg/m2 and absence of a first-degree relative with Type 2 diabetes), 24-28 weeks TNF-alpha levels are highly associated with corresponding insulin and HOMA values in the same model (respectively, beta=0.27; 95%CI 0.11-0.43; p=0.001 and beta=0.30; 95%CI 0.14-0.46; p<0.001). CONCLUSIONS: The data support the developing hypothesis that low-grade systemic inflammation is associated to GDM, in particular for pregnant women without conventional risk factors for gestational hyperglycemia, whose insulin resistance seems less explainable.

Adult↗
PubMed2004

Rapid prenatal diagnosis of common chromosome aneuploidies by QF-PCR. Assessment on 18,000 consecutive clinical samples.

The quantitative fluorescent PCR (QF-PCR) assay, introduced during the last few years, allows prenatal diagnoses of common chromosome aneuploidies in a few hours after sampling. We report the first assessment of QF-PCR performed on a large cohort of 18,000 consecutive clinical specimens analysed in two different Centres. All samples were analysed by QF-PCR using several selected STR markers together with amelogenin and, occasionally, SRY for fetal sexing. Results were compared with those obtained by conventional cytogenetic analysis. In 17,129 tests, normal fetuses were detected by QF-PCR. No false positives were observed. All 732 cases of trisomy 21, 18, 13, triploidies, double trisomies as well as all but one fetuses with X and Y aneuploidies were correctly diagnosed. Chromosome mosaicism could also be suspected in several samples. In some cases of in vitro culture failures, QF-PCR was the only evidence of fetal X, Y, 21, 18 and 13 chromosome complement. QF-PCR proved to be efficient and reliable in detecting major numerical chromosome disorders. The main advantages of the molecular assay are its very low cost, speed and automation enabling a single operator to perform up to 40 assays per day. QF-PCR relieves anxiety of most parents within 24 h from sampling and accelerates therapeutic interventions in the case of an abnormal result. In countries where large scale conventional cytogenetics is hampered by its high cost and lack of technical expertise, QF-PCR may be used as the only prenatal diagnostic test.

Aneuploidy↗
PubMed2004

Methylation of tumor suppressor gene p16 and prognosis of epithelial ovarian cancer.

OBJECTIVE: Methylation of p16 promoter was evaluated in ovarian cancer to determine the role of p16 methylation in ovarian cancer prognosis. METHODS: Two hundred and forty-nine patients with primary epithelial ovarian cancer were selected for the study; these patients were followed for a median of 31 months. Genomic DNA extracted from fresh frozen tumor tissues were treated with sodium bisulfite and were analyzed for p16 methylation using methylation-specific PCR (MSP). Cox regression survival analysis was performed to examine the associations of p16 methylation with progression-free and overall survivals. RESULTS: Of the 249 patients, 100 (40%) were tested positive for p16 promoter methylation. The status of p16 methylation did not change significantly with patient age, disease stage, histological grade, residual tumor size, and debulking results, although p16 methylation seemed to occur more often in patients with advanced diseases or aggressive tumors. Compared to those without p16 methylation, patients with p16 methylation had significantly higher risk for disease progression (P = 0.01). The relative risk for progression was 1.69 (95% CI: 1.12-2.54), and the association remained statistically significant (RR = 1.54, 95% CI: 1.01-2.34) after adjusting for clinical and pathological variables. The risk for death was also higher in methylation positive patients than in methylation negative patients (RR = 1.33, 95% CI: 0.88-2.00), but the difference was not statistically significant. CONCLUSION: The study suggests that promoter methylation in the p16 gene is associated with ovarian cancer progression, and evaluation of p16 methylation may have values in predicting ovarian cancer prognosis.

Adult↗
PubMed2003

Obesity or diabetes: what is worse for the mother and for the baby?

OBJECTIVES: The aim of the present study is to evaluate pregnancy outcomes in a cohort of Caucasian pregnant women in relation to their body mass index and glucose tolerance status; the role of central fat distribution, as indicated by waist-to-hip circumference ratio, was also considered. METHODS: Seven hundred women were studied; they had gestational diabetes or impaired glucose tolerance (250) or normoglycaemia (450). Among them 117 had pre-pregnancy overweight/obesity (44 were obese), 133 hyperglycaemia, but normal weight, and 117 hyperglycaemia and overweight/obesity (42 were obese). RESULTS: Hypertension, cesarean delivery and prevalence of large-for-gestational age babies were higher in obese (both with normoglycaemia and hyperglycaemia), mainly in those with greater gestational weight gain and central fat distribution (waist-to-hip ratio > 0.90). Normal weight hyperglycaemic women showed better outcomes than obese normoglycaemic women did. In a multiple logistic regression model, obesity (OR=10.6; 95% CI 5.00-22.54) was directly related to hypertension, and independent predictors of cesarean section were: gestational hyperglycaemia (OR=1.78; 95% CI 1.21-2.62), gestational weight gain (OR=1.06; 95% CI 1.02-1.10), and central obesity (OR=1.51; 95% CI 1.02-2.24), while obesity (OR=4.48; 95% CI 2.30-8.71) gestational weight gain (OR=1.08; 95% CI 1.03-1.12) and central fat distribution (OR=1.81: 95% CI 1.12-2.93) were directly related to delivering larger babies, after multiple adjustments. CONCLUSION: These results suggest that pre-pregnancy obesity and gestational hyperglycaemia were independent risk factors for different adverse pregnancy and neonatal outcomes, while central distribution of fat, and gestational weight gain play an additive adverse role on these outcomes.

Adult↗
PubMed2003

Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to beta-cell antigens.

AIMS: To evaluate the prevalence of beta-cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies. METHODS: One hundred and twenty-three pregnant patients with gestational diabetes, 84 with impaired glucose tolerance and 290 with normoglycaemia were evaluated for anti-islet cell antibodies, glutamic acid decarboxylase (GAD) autoantibodies, and the components of the metabolic syndrome. RESULTS: Autoantibody positivity was 8.9%, 17.9% and 0.3% in patients with diabetes, impaired tolerance and normoglycaemia, respectively. Hyperglycaemic patients with autoantibodies had lower body mass index, waist, weight gain at the time of the screening test and a lower percentage of previous pregnancies than those without autoantibodies. In addition, their fasting insulin values were significantly lower and inversely related to the presence of autoantibodies (odds ratio (OR) = 0.64; 95% confidence interval (CI) 0.42-0.96), the lowest values being found in anti-GAD+ patients. Autoantibody-positive women with diabetes were more frequently treated with insulin than negative patients (OR = 7.21; 95% CI 1.85-28.08). CONCLUSIONS: Autoantibody-positive women with gestational hyperglycaemia displayed fewer features of insulin resistance and required more frequent insulin therapy than negative women and presumably had presymptomatic Type 1 diabetes. If this conclusion is corroborated by the follow-up of larger series, clinical and immunological distinction of types of gestational hyperglycaemia would be useful.

Adult↗
PubMed2003

[Use of antibiotics in prevention and therapy in obstetrics and gynaecologic surgery].

BACKGROUND: The antibiotic treatments employed in 1999 in cases of gynaecologic and obstetric surgery in the first clinic of the Gynaecology and Obstetrics Department of the University of Turin have been evaluated. METHODS: 1131 gynaecological operations (major interventions, minor interventions, laparoscopies) and 492 laparotomic operations in obstetrics (mostly Cesareans) were assessed. Modalities of administration of chemoantibiotics (CAB) both at the prophylaxis stage and during the therapy stage were evaluated. RESULTS: A great application of chemoantibiotic prophylaxis (CABP) was noted as regards the gynaecological interventions (57.4% of cases) and low resort to chemoantibiotic therapy (CABT) (9%), thus highlighting the effectiveness of prophylaxis in reducing the incidence of infectious complications in the postoperative course in gynaecological surgery. As for obstetrics, the low percentage resort to CABP (36%) and the high resort to CABT (26%) were noted. It is proposed to obviate this fact by increasing the number of cases of CABP for obstetrics so as to reduce the massive recourse to CABT. CONCLUSIONS: Finally, some pharmacoeconomic remarks are offered regarding the rationalisation of the use of CABs in hospital surgical obstetrics and gynaecology.

Antibiotic Prophylaxis↗
PubMed2002

Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker.

Human kallikrein 6 protein is a newly discovered human kallikrein. We determined the amount of human kallikrein 6 in extracts of 182 ovarian tumours and correlated specific activity (ng hK6 mg(-1) total protein) with clinicopathological variables documented at the time of surgical excision and with outcome (progression free survival, overall survival) monitored over a median interval of 62 months. Thirty per cent of the tumours were positive for human kallikrein 6 (>35 ng hK6 mg(-1) total protein). Human kallikrein 6-specific immunohistochemical staining of four ovarian tissues that included benign, borderline and malignant lesions indicated a cytoplasmic location of human kallikrein 6 in tumour cells of epithelial origin, although the intensity of staining was variable. Tumour human kallikrein 6 (ng hK6 mg(-1) total protein) was higher in late stage disease, serous histotype, residual tumour >1 cm and suboptimal debulking (>1 cm) (P<0.05). Univariate analysis revealed that patients with tumour human kallikrein 6 positive specific activity were more likely to suffer progressive disease and to die (hazard ratio 1.71 (P=0.015) and 1.88 (P=0.022), respectively). Survival curves demonstrated the same (P=0.013 and 0.019, respectively). Multivariate analysis revealed that human kallikrein 6 positivity was retained as an independent prognostic variable in several subgroups of patients, namely those with (low) grade I and II tumours (hazard ratio progression free survival 4.3 (P=0.027) and overall survival 4.1 (P=0.023)) and those with optimal debulking (hazard ratio progression free survival 3.8 (P=0.019) and overall survival 5.6 (P=0.011)). We conclude that tumour kallikrein 6 protein levels have utility as an independent adverse prognostic marker in a subgroup of ovarian cancer patients with otherwise apparently good prognosis.

Adult↗
PubMed2002

[Expression and prognostic significance in epithelial ovarian cancer].

BACKGROUND: Insulin-like growth factor binding protein-3 (IGFBP-3) is a glycoprotein with specific binding affinity to peptide hormones insulin-like growth factors (IGFs) which are potent mitogens for a variety of cells. IGFBP-3 can inhibit the activities of IGFs by interfering with the interaction between IGFs and their receptor IGF-IR. Epithelial ovarian cancer (EOC) tissues express IGFBP-3, IGFs and IGF-IR. Moreover, high levels of IGF-I and IGF-IR have been shown in epithelial ovarian cancer, and IGF-I stimulates the growth of ovarian cancer. METHODS: We measured IGFBP-3 levels in ovarian cancer tissues of 147 consecutive patients and we examined its association with clinical and pathological features of the disease and patient survival. The average age of the patients in the study was 55 years and the median follow-up time was 37 months. IGFBP-3 levels were measured in the tissue extracts by a commercial ELISA kit and non-parametric statistics and the Cox regression survival analysis were used to determine the associations of IGFBP-3 with clinical and pathologic variables as well as with patient survival. RESULTS: High IGFBP-3 levels resulted significantly associated with some of the favorable prognostic features of the disease, including early clinical stage (p=0.048), small size of residual tumor (p=0.007), and optimal debulking result (p=0.007). High IGFBP-3 was also associated with a significantly reduced risk for disease progression (RR=0.52, p=0.034) and we showed an inverse dose-dependent relationship between IGFBP-3 and disease progression-free survival (p=0.033). However, the association with disease progression-free survival was no longer statistically significant in a multivariate analysis. An association between IGFBP-3 and overall survival was not shown. CONCLUSIONS: This study suggest that IGFBP-3 may play a role in the progression of epithelial ovarian cancer.

Adult↗
PubMed2002

[Growth factors in epithelial ovarian cancer].

The aim of this study was to provide an up-to-date review of the knowledge on the role of the main growth factors involved in the onset and progression of epithelial ovarian cancer (Transforming Growth Factor a-TGFa, Trans-forming Growth Factor-TGFb, Epidermal Growth Factor-EGF, Insulin-Like Growth Factor-IGF, Vascular Endothelial Growth Factor-VEGF). Relevant articles published between 1991 and 2001 were identified using the Medline database. Publications identified by the search were reviewed and critically evaluated for their relevance to growth factors role in ovarian cancer. This review may be useful for clinicians wishing to study the biological mechanisms involved in epithelial ovarian neoplasms, in order to evaluate the possible value of Growth Factors as prognostic or predictive markers which could lead to novel therapeutic regimens, fitting individual needs based on single biological variations.

Carcinoma↗
PubMed2001

Quantitative expression of the human kallikrein gene 9 (KLK9) in ovarian cancer: a new independent and favorable prognostic marker.

Many members of the human kallikrein gene family were found to be differentially expressed in various malignancies and some are useful cancer diagnostic/prognostic markers. KLK9 is a newly discovered human kallikrein gene that is expressed in several tissues including thymus, testis, spinal cord, salivary gland, ovary, and skin. Like other kallikreins, the KLK9 gene was found to be regulated by steroid hormones in cancer cell lines. Our purpose is to examine whether quantitative analysis of KLK9 expression has prognostic value in ovarian cancer. We studied the expression of KLK9 by quantitative reverse transcription-PCR in 168 consecutive ovarian tumors of different stages, grades, and histological types, and correlated the expression with clinicopathological parameters, response to chemotherapy, and patients' survival. We found that KLK9 expression was significantly higher in patients with early disease stages (I or II; P = 0.044) and in patients with optimal debulking (P = 0.019). Kaplan-Meier survival curves demonstrated that patients with KLK9-positive tumors have substantially longer progression-free and overall survival (P < 0.001 and P = 0.016, respectively). When the Cox proportional hazard regression analysis was applied to subgroups of patients, KLK9 expression was found to be a significant predictor of progression-free survival in the subgroup of patients with low-grade tumors [hazard ratio (HR), 0.13; P = 0.0015], early stage (HR, 0.099; P = 0.031); and those with optimal debulking (HR, 0.26; P = 0.012). After adjusting for other known prognostic variables, KLK9 retained its independent prognostic value in all of these subgroups of patients. A negative correlation was found between the expression levels of CA125 and KLK9 (rs, 0.350; P = 0.002). Our results indicate that KLK9 is under steroid hormone regulation in ovarian and breast cancer cell lines. Immmunohistochemically, human kallikrein protein (hK9) was localized in the cytoplasm, but not in the nuclei, of the epithelial cells of ovarian cancer tissues. We conclude that KLK9 is a potential new independent favorable prognostic marker for early stage, low-grade, optimally debulked ovarian cancer patients.

Adult↗
PubMed2001

Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in ovarian cancer.

Kallikrein gene 5 (KLK5, also known as KLK-L2), located on chromosome 19q13.4, is one of the newly identified members of the kallikrein gene family, which is a subgroup of the serine protease enzyme family. In normal human tissues, KLK5 is highly expressed in skin, mammary gland and testis. Preliminary RT-PCR analysis has indicated that KLK5 is expressed in a subset of ovarian tumours. We have thus hypothesized that KLK5 may be a new prognostic indicator in ovarian cancer. We have examined the mRNA expression of KLK5 in 142 malignant ovarian tissues. Tumours were pulverized, total RNA was extracted, and cDNA was prepared by reverse transcription. KLK5 was amplified by PCR using gene specific primers, and the identity of the PCR product was verified by sequencing. Ovarian tissues were then classified as KLK5 positive or negative, based on ethidium bromide staining of the PCR product on agarose gels. KLK5 was found to be highly expressed in 58/142 (41%) of ovarian cancer samples while its level of expression was very low in normal ovarian tissues. We found a strong positive relation between KLK5 expression and tumour grade (P = 0.006) and disease stage (P = 0.027). Univariate survival analysis revealed that patients with ovarian tumours positive for KLK5 expression had an increased risk for relapse and death (P = 0.018 and 0.022, respectively). In multivariate analysis, KLK5 expression showed independent prognostic value only in the subset of tumours with lower grade disease (grades I and II). We conclude that KLK5 expression is associated with more aggressive forms of epithelial ovarian carcinoma and has indepdent prognostic value in low grade tumours.

Adult↗