Outcomes of prostate cancer screening among men using antidiabetic medication.

Diabetic men have decreased risk for prostate cancer (PCa) overall and lower PSA compared to non-diabetics. This may affect the outcomes of PSA-based screening. We investigated the effect of PSA-based screening at 4-year intervals on PCa incidence and mortality separately among users and non-users of antidiabetic medication with the hypothesis that screening would detect less low-grade cancer and more high-grade cancer in diabetic men. A cohort of 80,458 men from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) were linked to national prescription database to obtain information on antidiabetic medication purchases. PCa risk and mortality were compared between the FinRSPC screening arm (SA) and the control arm (CA) separately among users and non-users of antidiabetic medication. Among antidiabetic medication users median PSA was lower than in non-users (0.93 and 1.09 ng/ml, respectively, P for difference = 0.001). Screening increased overall PCa incidence compared to CA after the first screen both among medication users and non-users (HR 1.31, 95% CI 1.08-1.60 and HR 1.55, 95% CI 1.44-1.66, respectively). On the second and third screen the difference between SA and CA attenuated only among medication users. Detection of Gleason 6 tumors was lower among medication users, whereas no difference was observed in detection of Gleason 8-10 cancers. Concordantly, screening affected PCa mortality similarly regardless of antidiabetic medication use (HR 0.38, 95% CI 0.14-1.07 and HR 0.19, 95% CI 0.11-0.33 among users and non-users after three screens, respectively. P for difference = 0.18). Median PSA is lower in men using antidiabetic drugs than among non-users. Systematic PSA screening detects less low-risk tumors among medication users, whereas detection of high-risk tumors and mortality effects are similar regardless of medication use. This suggests that antidiabetic medication users may form a suitable target group for PCa screening, with less screening-related overdiagnosis of indolent tumors.

Desmosterol accumulation in users of amiodarone.

BACKGROUND: Amiodarone is an effective and widely used antiarrhythmic drug with many possible adverse effects including hypercholesterolaemia and hepatotoxicity. OBJECTIVE: Our aim was to evaluate how long-term amiodarone treatment affects cholesterol metabolism. METHODS: The study population consisted of 56 cardiac patients, of whom 20 were on amiodarone (amiodarone + group) and 36 did not use the drug (amiodarone - group). We also studied a control group of 124 individuals selected randomly from the population. Cholesterol metabolism was evaluated by analysis of serum noncholesterol sterols by gas-liquid chromatography and gas chromatography-mass spectrometry. RESULTS: Comparisons of serum lipids and noncholesterol sterols across the three groups showed increased serum triglyceride in users of amiodarone but no statistically significant group differences in total, LDL or HDL cholesterol or serum proprotein convertase subtilisin/kexin type 9 concentrations. Nor did the groups differ in the ratios of cholestanol or plant sterols to cholesterol in serum, suggesting that cholesterol absorption was unaltered. However, all users of amiodarone had very markedly elevated serum desmosterol concentrations: the desmosterol-to-cholesterol ratio (102 × µmol mmol-1 ) averaged 1030.7 ± 115.7 (mean ± SE) in the amiodarone + group versus 82.7 ± 3.4 and 75.9 ± 1.4 in the amiodarone - and the population control groups (P < 0.001), respectively. CONCLUSION: Use of amiodarone was associated with on average 12-fold serum desmosterol concentrations compared with the control groups. This observation is fully novel and suggests that amiodarone interferes with the conversion of desmosterol to cholesterol in the cholesterol synthesis pathway. Whether accumulation of desmosterol plays a role in amiodarone-induced hepatotoxicity deserves to be studied in the future.

Prostate cancer risk and nonsteroidal antiinflammatory drug use in the Finnish prostate cancer screening trial.

BACKGROUND: The association between nonsteroidal antiinflammatory drugs (NSAIDs) and prostate cancer risk remains controversial. We examined the risk among NSAID users in 78 615 men in the Finnish Prostate Cancer Screening Trial. METHODS: We obtained information on NSAID prescription usage from Finnish nationwide prescription database and on over-the-counter use by a questionnaire. Prostate cancer cases were identified from the Finnish Cancer Registry. RESULTS: Prostate cancer risk was elevated among current NSAID prescription users irrespective of screening (hazard ratio (HR)=1.45, confidence interval (95% CI)=1.33-1.59 and HR=1.71, 95% CI=1.58-1.86 in the screening and control arm, respectively), but not for previous use of NSAIDs. The risk increase was similar among coxib and acetaminophen current users, and stronger for metastatic prostate cancer (HR=2.41, 95% CI=1.59-3.67 and HR=3.44, 95% CI=2.60-4.55 in the screening and control arm, respectively). Previous use of NSAIDs, aspirin use and over-the-counter NSAID usage were not associated with prostate cancer. CONCLUSIONS: Differing association for current and previous use suggests that the risk increase is unlikely to be directly caused by the medication, but may be due to the conditions indicating NSAID prescription usage, such as symptoms of undiagnosed prostate cancer. To reduce inconsistency between the study outcomes, future epidemiological studies on NSAID use and prostate cancer risk should assess the indications for NSAID usage.

Candidate epitopes for measurement of hCG and related molecules: the second ISOBM TD-7 workshop.

Participants of the Second International Workshop (WS) on human chorionic gonadotropin (hCG) of the International Society of Oncology and Biomarkers Tissue Differentiation 7 (ISOBM TD-7) have characterized in detail a panel of 69 antibodies (Abs) directed against hCG and hCG-related variants that were submitted by eight companies and research groups. Specificities of the Abs were determined using the First WHO International Reference Reagents for six hCG variants, i.e., hCG, hCGn, hCGß, hCGßn, hCGßcf, and hCGα, which are calibrated in SI units, and hLH. Molecular epitope localizations were assigned to the ISOBM-mAbs by comparing ISOBM-Ab specificity, sandwich compatibility, and mutual inhibition profiles, to those of 17 reference monoclonal (m)Abs of known molecular epitope specificities. It appeared that 48 Abs recognized hCGß-, 8 hCGα-, and 13 αß-heterodimer-specific epitopes. Twenty-seven mAbs were of pan hCG specificity, two thereof with no (<0.1%; epitope ß1), 12 with low (<1.0%; epitopes ß2/4), and 13 with high (>>1%; epitopes ß3/5) hLH cross-reactivity. The majority of hCGß epitopes recognized were located in two major antigenic domains, one on the peptide chain of the tips of ß-sheet loops 1 and 3 (epitopes ß2-6; 27 mAbs) and the second around the cystine knot (e.g., epitopes ß1, ß7, and ß10; 9 mAbs). Four mAbs recognized epitopes on hCGßcf-only (e.g., epitopes ß11 and ß13) and six mAbs epitopes on the remote hCGß-carboxyl-terminal peptide (epitopes ß8 and ß9 corresponding to amino acids 135-144 and 111-116, respectively). For routine diagnostic measurements, methods are used that either detect hCG-only, hCGß-only, or hCG together with hCGß or hCG together with hCGß and hCGßcf. Sandwich assays that measure hCG plus hCGß and eventually hCGßcf should recognize the protein backbone of the analytes preferably on an equimolar basis, should not cross-react with hLH and not be susceptible to blunting of signal by nonmeasured variants like hCGßcf. Such assays can be constructed using pairs of mAbs directed against the cystine knot-associated epitope ß1 (Asp10, Asp60, and Gln89) in combination with epitopes ß2 or ß4 located at the top of ß-sheet loops 1 + 3 of hCGß involving aa hCGß20-25 + 68-77. In summary, the results of the First and Second ISOBM TD-7 WSs on hCG provide the basis for harmonization of specificities and epitopes of mAbs to be used in multifunctional and selective diagnostic hCG methods for different clinical purposes.

First trimester hyperglycosylated human chorionic gonadotrophin in serum - a marker of early-onset preeclampsia.

INTRODUCTION: Recent studies indicate that treatment with low-dose aspirin may reduce the risk of preeclampsia. Thus, early prediction of preeclampsia is needed. Low serum concentrations of hyperglycosylated human chorionic gonadotrophin (hCG-h) are associated with early pregnancy loss. We therefore studied whether it may serve as an early marker of preeclampsia. METHODS: A nested case-control study included 158 women with subsequent preeclampsia, 41 with gestational hypertension, 81 normotensive women giving birth to small-for-gestational-age (SGA) infants and 427 controls participating in first trimester screening for Down's syndrome between 8 and 13 weeks of gestation. Gestational-age-adjusted multiples of medians (MoMs) were calculated for serum concentrations of hCG-h, the free beta subunit of hCG (hCGß) and pregnancy-associated plasma placental protein A (PAPP-A) and the proportion of hCG-h to hCG (%hCG-h). Clinical risk factors including mean arterial pressure (MAP) and parity were also included in the risk calculation. RESULTS: In women with subsequent preeclampsia %hCG-h was lower than in controls (median MoM 0.92, P < 0.001), especially in 29 cases with early-onset preeclampsia (0.86, P < 0.001), in which PAPP-A also was reduced (0.95, P = 0.001). At 90% specificity for prediction of early-onset preeclampsia, sensitivity was 56% (95% confidence interval, 52-61%) for %hCG-h, 33% (28-37%) for PAPP-A, and 69% (51-83%) for the combination of these with first trimester MAP and parity. The area under the receiver-operating characteristic (ROC) curve for the combination of all these was 0.863 (0.791-0.935). CONCLUSIONS: hCG-h is a promising first trimester marker for early-onset preeclampsia. Addition of PAPP-A and maternal risk factors may improve the results.

A high-density tissue microarray from patients with clinically localized prostate cancer reveals ERG and TATI exclusivity in tumor cells.

BACKGROUND: Prostate cancer (PCa) is characterized by high tumor heterogeneity. In 2005, the fusion between the androgen-regulated gene TMPRSS2 and members of the ETS family was discovered in prostate cancer. In particular, fusion of TMPRSS2 with ERG was found in approximately 50% of prostate cancers and considered as an early event in the onset of the disease. The prognostic value of this fusion is still contradictory. Bioinformatics showed that overexpression of SPINK1 gene in a subset of fusion-gene-negative prostate cancers was associated with a poor prognosis. In theory, overexpression of the tumor-associated trypsin inhibitor (TATI) protein encoded by SPINK1 in fusion-gene-negative tumor cells opens the way to selected treatments for genotypically different cases. However, their expression has never been assessed at the cellular level in the same tissue samples. METHODS: As ERG expression has been shown to be a surrogate of fusion gene occurrence in prostate cancer, we have used double immunohistochemical staining to assess expression of ERG and TATI on a large tissue microarray comprising 4177 cases of localized prostate cancer. RESULTS: We did not detect any co-expression of ERG and TATI in the same cancer cells, which confirms previous suggestions from in silico studies. ERG was associated with Gleason score (GS), surgical margins and pathological stage, but had no prognostic value in this cohort. TATI was weakly associated with pathological stage but had no significant association with outcome. CONCLUSIONS: We here provide a morphological basis for ERG and TATI exclusivity in prostate cancer cells. Future therapies should be based on a combination of different targets in order to eradicate tumor cells with gene fusions and cells expressing other tumor-associated antigens. Further studies are needed to understand why ERG and TATI are not co-expressed in the same prostatic tumor cells.

OS009. Second trimester serum hyperglycosylated human chorionic gonadotrophin and preeclampsia.

INTRODUCTION: Hyperglycosylated human chorionic gonadotrophin (hCG-h), produced by the placental trophoblast cells, is involved in placental development in early pregnancy. Decreased second trimester urine hCG-h is associated with later preeclampsia, which may be a sign of impaired trophoblastic invasion preceding symptoms of the disease. OBJECTIVES: To study whether maternal second trimester serum hCG-h concentrations predict later development of preeclampsia. METHODS: Fifty-five women with subsequent preeclampsia, 21 women with gestational hypertension, 30 normotensive women with small-for-gestational-age (SGA) infants and 83 controls with uneventful pregnancies were included in the study. Their serum hCG and hCG-h concentrations were analyzed by fluoroimmunoassay at 14-17weeks of gestation. The proportion of hCG-h of total hCG (%hCG-h) was calculated and converted to multiples of the median (MoMs) of the controls. MoMs of the groups were compared by Mann-Whitney U test. Pearson's correlation was used to analyze correlations between clinical characteristics and serum marker concentrations. The results are given as medians with 95% confidence intervals (95% CI). A two-tailed P<0.05 was considered significant. RESULTS: The concentrations of hCG-h and %hCG-h decreased with advancing gestational weeks in women with subsequent preeclampsia (r=-0.289, p=0.032 and r=-0.464, p<0.001), but not in women in the other groups. There was a tendency towards lower concentrations of hCG-h and %hCG-h in women with subsequent preeclampsia than in controls. The median MoMs of %hCG-h were 0.89 (95% CI,0.79-1.00) in women with subsequent preeclampsia and 1.00 (0.91-1.11) in controls. The corresponding values for women with subsequent gestational hypertension were 1.00 (0.86-1.16), for those with subsequent SGA infants they were 1.09 (0.89-1.23). The difference between preeclampsia and the other groups together was significant (p=0.029). CONCLUSION: Earlier studies suggest that decreased urine hCG-h concentrations reflect changes in placental function that precede the development of preeclampsia. At 14-17weeks of gestation, the serum concentrations of hCG-h showed moderate validity to predict later development of preeclampsia. Further studies on the utility of hCG-h for prediction of subsequent preeclampsia are warranted.

Stability of first trimester placental growth factor in serum and whole blood.

BACKGROUND: Placental growth factor (PlGF) is a proposed first-trimester screening marker for pre-eclampsia. This study investigates the stability of PlGF in serum and whole blood at typical routine storage temperatures. METHODS: Serum pools were stored at refrigerator temperature, room temperature or 30 °C for up to 30 days, or exposed to up to six freeze-thaw cycles. Whole blood was stored at room temperature or 30 °C for up to 6 days. PlGF was quantified using a DELFIA Xpress analyser. RESULTS: Placental growth factor levels increased over time, seemingly because of the dissociation of PlGF bound to a soluble binding protein, sFlt-1. Increase was slow in serum at refrigerator temperature, remaining stable (less than 10% change from start point) for at least 30 days. At room temperature PlGF was stable for 3.3 days and at 30 °C for 1 day. Serum PlGF remained stable for at least six freeze-thaw cycles. In whole blood, instability was worse, being stable for only 19.4 h at room temperature and just 3.3 h at 30 °C. CONCLUSION: Routine screening of sample handling requires careful monitoring. However, no extra precautions need to be taken when PlGF is used for pre-eclampsia screening run alongside existing first trimester aneuploidy screening programs that include hCGß.

Changes in serum concentrations of soluble vascular endothelial growth factor receptor-1 after pregnancy.

BACKGROUND: Vascular endothelial growth factor (VEGF) is the most potent stimulator of angiogenesis. It mediates its activity through two membrane-bound receptors, VEGFR-1 and VEGFR-2, both expressed in the placenta. Beginning in early pregnancy, the soluble form of the first, sVEGFR-1, binds and inhibits most of the biological actions of circulating VEGF. After delivery, it disappears from the maternal circulation. METHODS: We determined the biological elimination rate of endogenous sVEGFR-1 after term pregnancy in serial venous samples obtained during and after elective Caesarean sections (n=8), and we demonstrated the relationship between serum sVEGFR-1 and VEGF after mid-trimester legal termination of pregnancy (n = 5), by analysing their concentrations using immunoassays (ELISA). RESULTS: The disappearance of sVEGFR-1 from circulation after Caesarean delivery was biphasic with a rapid half-life of 3.4 h (2.2-7.5 h; median, range) and a slow one of 29 h (17-94 h). After mid-trimester legal termination of pregnancy the sVEGFR-1 concentrations decreased and those of free VEGF simultaneously increased with a highly significant negative correlation with each other (r = -0.90, P < 0.0001). CONCLUSIONS: The disappearance of endogenous sVEGFR-1 after pregnancy is biphasic, and it is associated with a simultaneous increase in free VEGF concentrations.

False-positive screening results in the Finnish prostate cancer screening trial.

BACKGROUND: There is evidence that prostate cancer (PC) screening with prostate-specific antigen (PSA) serum test decreases PC mortality, but screening has adverse effects, such as a high false-positive (FP) rate. We investigated the proportion of FPs in a population-based randomised screening trial in Finland. METHODS: Finland is the largest centre in the European Randomized Study of Screening for Prostate Cancer. We have completed three screening rounds with a 4-year screening interval (mean follow-up time 9.2 years) using a PSA cutoff level of 4.0 ng ml(-1); in addition, men with PSA 3.0-3.9 and a positive auxiliary test were referred. An FP result was defined as a positive screening result without cancer in biopsy within 1 year from the screening test. RESULTS: The proportion of FP screening results varied from 3.3 to 12.1% per round. Of the screened men, 12.5% had at least one FP during three rounds. The risk of next-round PC following an FP result was 12.3-19.7 vs 1.4-3.7% following a screen-negative result (depending on the screening round), risk ratio 3.6-9.9. More than half of the men with one FP result had another one at a subsequent screen. Men with an FP result were 1.5 to 2.0 times more likely to not participate in subsequent rounds compared with men with a normal screening result (21.6-29.6 vs 14.0-16.7%). CONCLUSION: An FP result is a common adverse effect of PC screening and affects at least every eighth man screened repeatedly, even when using a relatively high cutoff level. False-positive men constitute a special group that receives unnecessary interventions but may harbour missed cancers. New strategies are needed for risk stratification in PC screening to minimise the proportion of FP men.

Prostate cancer incidence among finasteride and alpha-blocker users in the Finnish Prostate Cancer Screening Trial.

BACKGROUND: The Prostate Cancer Prevention Trial has shown a protective effect of finasteride on prostate cancer in low-risk men. It is uncertain whether similar results can be expected when finasteride is used to treat benign prostatic hyperplasia. METHODS: We performed an observational cohort study within the Finnish Prostate Cancer Screening Trial. Using a comprehensive prescription database on medication reimbursements during 1995-2004 of men using finasteride or alpha-blockers for benign prostatic hyperplasia, we evaluated prostate cancer incidence among 23 320 men screened during 1996-2004. RESULTS: Compared to medication non-users, overall prostate cancer incidence was not significantly affected in finasteride users (hazard ratio 0.87; 95% CI 0.63-1.19). Incidence of Gleason 2-6 tumours, however, was decreased among finasteride users (HR 0.59; 95% CI 0.38-0.91), whereas incidence of Gleason 7-10 tumours was unchanged (HR 1.33; 95% CI 0.77-2.30). The protective effect concerned mainly screen-detected tumours. Overall prostate cancer risk was not significantly reduced among alpha-blocker users relative to non-users, but decreased incidence of high-grade tumours was observed (0.55; 95% CI 0.31-0.96). CONCLUSIONS: The detection of low-grade, early-stage tumours is decreased among men who use finasteride for symptomatic BPH. The protective effect of finasteride can also be expected in men with benign prostatic hyperplasia.

High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer.

Increased expression of tumour-associated trypsin inhibitor (TATI) in tumour tissue and/or serum has been associated with poor survival in various cancer forms. Moreover, a proinvasive function of TATI has been shown in colon cancer cell lines. In this study, we have examined the prognostic significance of tumour-specific TATI expression in colorectal cancer, assessed by immunohistochemistry (IHC) on tissue microarrays (TMAs) with tumour specimens from two independent patient cohorts. Kaplan-Meier analysis and Cox proportional hazards modelling were used to estimate time to recurrence, disease-free survival and overall survival. In both cohorts, a high (>50% of tumour cells) TATI expression was an independent predictor of a significantly shorter overall survival. In cohort II, in multivariate analysis including age, gender, disease stage, differentiation grade, vascular invasion and carcinoembryonal antigen (CEA), high TATI expression was associated with a significantly decreased overall survival (HR=1.82; 95% CI=1.19-2.79) and disease-free survival (HR=1.56; 95% CI=1.05-2.32) in curatively treated patients. Moreover, there was an increased risk for liver metastasis in both cohorts that remained significant in multivariate analysis in cohort II (HR=2.85; 95% CI=1.43-5.66). In conclusion, high TATI expression is associated with liver metastasis and is an independent predictor of poor prognosis in patients with colorectal cancer.

Nexin-1 inhibits the activity of human brain trypsin.

Trypsin and other trypsin-like serine proteases have been shown to play important roles in neural development, plasticity and neurodegeneration. Their activity is modulated by serine protease inhibitors, serpins. However, for human brain trypsin, trypsin-4, no brain-derived inhibitors have been described. Here, we report that nexin-1 inhibits trypsin-4, and forms stable complexes only with this trypsin-isoenzyme. This result suggests that nexin-1 could modulate trypsin activity in brain where both nexin-1 and trypsin-4 are expressed.

Safety assessment of common foods enriched with natural nonesterified plant sterols.

BACKGROUND/OBJECTIVES: To assess safety during a diet based on low-fat foods enriched with nonesterified wood-derived plant sterols and mineral nutrients related to serum phytosterol, sex hormone and fat-soluble vitamin metabolism. SUBJECTS/METHODS: Seventy-one study participants (52 women, 19 men) with mild-to-moderate hypercholesterolemia completed the double-blind, placebo-controlled feeding trial lasting for 15 weeks. The subjects were randomly allocated to the sterol group receiving food items enriched with mineral nutrients as well as with a total of 1.25, 2.5 and 5.0 g per day of plant sterols during the first, second and third 5-week periods, respectively, or to the placebo group receiving similar food items without plant sterols. This outpatient clinical trial with free-living subjects was carried out at two hospital clinics. RESULTS: Two significant findings were observed. Serum sitosterol concentrations increased from 2.84 to 5.35 mg l(-1) (P<0.004 vs placebo) but those of serum total plant sterols did not because of compensatory changes in other phytosterols. The highest plant sterol levels did not exceed 0.6% of total serum sterols. Serum alpha-tocopherol concentrations decreased in the sterol group by 10% (P<0.0002), but the between-group difference disappeared after adjusting for the change in the carrier (LDL cholesterol). CONCLUSIONS: Fifteen-week consumption of natural nonesterified plant sterol-enriched food does not cause any serious adverse effects during such a period. However, serum alpha-tocopherol levels were somewhat reduced in the sterol group suggesting that long-term effects of plant sterols on serum fat-soluble vitamin concentrations should be further explored, especially in relation to very low-fat diets.

Extended release of adenovirus from silica implants in vitro and in vivo.

Despite promising preclinical results, the clinical benefits of cancer gene therapy have been modest heretofore. The main obstacle continues to be the level and persistence of gene delivery to sufficiently large areas of the tumor. One approach for overcoming this might entail extended local virus release. We studied the utility of silica gel monoliths for delivery of adenovirus to advanced orthotopic gastric and pancreatic cancer tumors. Initially, the biochemical properties of the silica-virus matrix were studied and nearly linear release as a function of time was detected. Virus stayed infective for weeks at +37 degrees C and months at +4 degrees C, which may facilitate storage and distribution. In vivo, extended release of functional replication deficient and also replication-competent, capsid-modified oncolytic viruses was seen. Treatment of mice with pancreatic cancer doubled their survival (P<0.001). Also, silica gel-based delivery slowed the development of antiadenovirus antibodies.

Gonadotropins in doping: pharmacological basis and detection of illicit use.

Parenteral administration of human chorionic gonadotropin (hCG) or luteinizing hormone (LH) stimulates the production of testosterone in males and these gonadotropins can therefore be used by athletes to enhance muscle strength. However, they are more expensive and less efficient than testosterone and anabolic steroids. Therefore their main use is probably to stimulate gonadal testosterone production during and after self-administration of testosterone or anabolic steroids. A positive effect of hCG on muscle strength has not been demonstrated in women and elevated concentrations of hCG in females are often caused by pregnancy. The use of gonadotropins is therefore prohibited only in males but not in females. HCG occurs at low but measurable concentrations in plasma and urine of healthy males and can be measured by sensitive methods. However, the characteristics of the method to be used for doping control have not been defined. Virtually all commercially available hCG assays have been designed for determination of hCG in serum rather than urine, which is used for doping control. Methods based on mass spectrometric detection of fragments derived from hCG extracted from urine by immunoadsorption have been developed but their suitability for doping control remains to be determined. The concentrations of LH in serum and urine are variable and more then 10-fold higher than those hCG. It is therefore difficult to detect illicit use of LH. The characteristics and reference values for hCG and LH assays used in doping control and the cutoff values need to be defined.

Human papillomavirus infection and primary fallopian tube carcinoma: a seroepidemiological study.

OBJECTIVE: To evaluate the role of human papillomavirus (HPV) types 6, 11, 16, 18, 31 or 33 infection in primary fallopian tube carcinoma (PFTC). DESIGN: A retrospective case-control study. SETTING: Department of Obstetrics and Gynaecology, Helsinki University Hospital, Finland. POPULATION: Seventy-eight consecutive women with PFTC diagnosed between 1985 and 2000 were studied. For each case, two healthy controls were selected. METHODS: Serum immunoglobulin G antibodies to HPV types 6, 11, 16, 18, 31 and 33 were measured from women with PFTC and their healthy controls. MAIN OUTCOME MEASURES: Analysis of HPV 6, 11, 18, 31 and 33 seropositivity among women with PFTC and controls. RESULTS: Seropositivity rates of non-oncogenic or oncogenic HPV types did not differ between cases and controls, odds ratios being 1.04-1.30 for oncogenic HPVs and 1.08-1.19 for non-oncogenic HPVs, similarly. We did not find any multiplicative joint effect in PFTC by antibodies to more than one oncogenic HPV type; neither did we find any antagonistic effect among women with antibodies to non-oncogenic and oncogenic HPV types. CONCLUSIONS: Our results do not suggest any link between PFTC and serological evidence for HPV infection.

Specificity of serum prostate-specific antigen determination in the Finnish prostate cancer screening trial.

Specificity constitutes a component of validity for a screening test. The number of false-positive (FP) results has been regarded as one of major shortcomings in prostate cancer screening. We estimated the specificity of serum prostate-specific antigen (PSA) determination in prostate cancer screening using data from a randomised, controlled screening trial conducted in Finland with 32 000 men in the screening arm. We calculated the specificity as the proportion of men with negative findings (screen negatives, SN) relative to those with negative and FP results (SN/(SN+FP)). A SN finding was defined as either PSA

Past chlamydial infection is not associated with primary fallopian tube carcinoma.

We conducted a retrospective seroepidemiological study to evaluate the relationship between past chlamydial infection and primary fallopian tube carcinoma (PFTC). Postoperative serum samples were drawn from 79 consecutive patients treated for PFTC in 1985-2000. For each case two controls were selected. Serum samples were analysed for IgG antibodies to different C. trachomatis serotype pools and to C. pneumoniae. Seropositivity in general or serum antibody levels to different C. trachomatis serovars or C. pneumoniae did not differ between PFTC patients and controls. The lack of association between anti-chlamydial antibodies and PFTC suggests that past chlamydial infection does not play a role in the etiopathogenesis of PFTC. However, because chlamydial infection is common at young age and PFTC develops decades later, we cannot definitively exclude the possibility that C.trachomatis contributes to the development of PFTC.

Differential expression of trypsinogen and tumor-associated trypsin inhibitor (TATI) in bladder cancer.

Tumor-associated trypsin inhibitor (TATI) is a marker of mucinous ovarian carcinoma, but it is also widely expressed in other malignant tumors and normal human tissues. Elevated serum concentrations of TATI are of prognostic value in ovarian, kidney, and bladder cancer. Tumor-associated trypsin is co-expressed with TATI in many malignancies and is thought to be involved in tumor invasion. TATI mRNA has been shown to be overexpressed in bladder cancer. We therefore studied whether trypsinogen expression also can be detected in bladder cancer and how this and TATI expression are associated with the clinicopathological characteristics of the tumors. We used RT-PCR, in situ hybridization and immunohistochemistry to detect trypsinogen- and TATI mRNA and protein in tissue samples from 28 bladder cancer patients and ten benign urothelia. TATI expression was detected in all benign tissues and non-invasive tumors. However, the expression was lower in the muscle-invasive tumors (pT2; n=5), whereas trypsinogen expression was seen in all but one non-invasive tumor. We conclude that trypsinogen is expressed in both malignant and benign bladder epithelium, whereas TATI expression decreases with increasing stage and grade of the tumor. This may suggest that a balanced expression of TATI and trypsinogen is required in normal tissue and that this balance is disrupted during tumor progression.