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Objective: The extracellular matrix glycoprotein tenascin-C has been proposed as a tumor marker with prognostic significance in many cancer forms, but in colorectal cancer, reported results have been controversial. The aim of this study was to evaluate the prognostic value of immunohistochemical tenascin-C expression in a series of 231 patients with colorectal cancer. Methods: Paraffin-embedded formalin-fixed specimens were stained with a tenascin-C-specific monoclonal antibody, and the stromal staining intensity and pattern were analyzed. Results: Tenascin-C immunoreactivity was observed in all 231 specimens, with a pattern of staining that was diffuse and interstitial. The staining was occasional in 39 (17%), moderate in 106 (46%) and strong in 86 specimens (37%). There was no statistically significant association between tenascin-C immunoreactivity and any of the other clinicopathological variables. The cumulative 5-year survival rates of patients with occasional and weak staining were similar (56.8 and 54.9%, respectively), while the patients with strong tenascin-C staining had a lower survival rate (46.1%). This difference in survival was not significant (p = 0.23). The staining pattern and distribution can be viewed from digitized representative microscope slides (virtual slides) at http://www.webmicroscope.net/supplements/tenascin. Conclusions: Our results indicate that immunohistochemical expression of tenascin-C is not of prognostic significance in colorectal cancer. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Loss of epithelial heparan sulfate proteoglycan syndecan-1 has been associated with a more aggressive behavior in various cancer forms, but the prognostic significance of syndecan-1 expression in colorectal cancer is unclear. The aim of this study was to evaluate the prognostic value of immunohistochemical syndecan-1 expression in a series of 237 patients with colorectal cancer. Methods: Paraffin-embedded formalin-fixed specimens were stained with a syndecan-1-specific monoclonal antibody, and both the epithelial and stromal expression were analyzed. Results: Epithelial expression of syndecan-1 was seen in 222 tumors (94%), and it was associated with low stage of disease (p = 0.002) and low histological differentiation grade (p = 0.048). The cumulative 5-year survival of patients with weak and strong syndecan-1 expression was 49 and 54 %, respectively (p = 0.234). Syndecan-1 stromal immunoreactivity was observed in 138 tumors (58%), but lacked prognostic significance. Staining pattern and distribution can be viewed from digitized representative microscope slides (virtual slides) at http://www.webmicroscope.net/supplements/syndecan. Conclusions: The results are in line with previous reports in that low epithelial syndecan-1 expression was associated with a higher histological grade and a more advanced clinical stage of the patients. This study shows that syndecan-1 is expressed also in stromal tissue of colorectal cancer, but it does not support the proposed role of stromal syndecan-1 expression as a marker of poor clinical outcome. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: p27 is a cyclin-dependent kinase inhibitor that prevents progression of the cell cycle from G1 phase. Postranscriptional loss of p27 correlates with poor prognosis in various solid tumors. In pancreatic cancer, the loss of p27 expression has been correlated with high tumor grade and advanced clinical stage, but data on its prognostic value are lacking. Method: In this retrospective study, the association between immunohistochemical p27 expression and prognosis was evaluated in 147 patients with pancreatic cancer using a commercial anti-Kip1/p27 monoclonal antibody. Result: p27 expression was generally low; in 103 of the 147 pancreatic cancer tumors examined, no nuclear staining was observed and in only 5 specimens did more than 50% of the nuclei stain, probably reflecting the aggressive nature of the disease. Loss of p27 expression was associated with poor prognosis in stage I–II pancreatic adenocarcinoma; the 5-year survival for p27 negative patients was 3.6% compared with 20% for p27-positive patients (p = 0.03). In a multivariate survival analysis in patients with stage I–II disease, p27 (HR 1.8) was a significant prognostic factor, independent of grade (RR 2.9). There was no association between p27 and other clinical variables. In conclusion, tissue expression of p27 is a significant predictor of 5-year survival in stage I–II pancreatic adenocarcinoma. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: Human chorionic gonadotropin (hCG) beta in serum is a promising tumour marker for gastrointestinal malignancies. Our aim was to investigate the expression of hCG beta by immunohistochemistry in various gastrointestinal cancers and benign tissues. Methods and results: A monoclonal antibody (MAb) specific for free hCG beta was used to stain 107 tissue samples from various gastrointestinal malignancies and 36 benign or normal tissue samples. The specificity of the staining was verified and the results compared with those obtained with a widely used commercial polyclonal antibody (PAb) which reacts with both free hCG beta and intact hCG, as well as with luteinizing hormone beta. With the MAb, we observed positive immunohistochemical staining in 24% of the malignant gastrointestinal tumours. Gastric (60%) and pancreatic (56%) carcinomas, as well as extrahepatic cholangiocarcinomas (36%), were positive most frequently. We also discovered immunoreactivity in half of the non-malignant samples from pancreatic and biliary tissues. With the PAb, hCG immunoreactivity was evident more frequently in some cancers, but the staining was diffuse and occasionally polymorphonuclear leucocytes were strongly stained. Conclusions: This study shows that our MAbs specific for hCG beta are well suited for immunohistochemistry. Our results confirm previous findings on gastrointestinal cancers and, furthermore, we demonstrate hCG beta tissue expression in pancreatic adenocarcinoma. The results support reports on hCG beta as a serum tumour marker for digestive tract diseases. [ABSTRACT FROM AUTHOR]

Background: Worldwide survival data for ductal adenocarcinoma of the pancreas are the lowest among the 60 most frequent types of organ cancers. Hence published data on long time survivors of this disease are controversial. We performed a nationwide study comprising all Finnish patients diagnosed with pancreatic cancer in the period 1990-1996 who survived for at least five years alter diagnosis. Methods: Data on patients registered as five year survivors of pancreatic cancer were obtained from the Finnish Cancer Registry and Statistics Finland. Slides or paraffin blocks were collected from patients recorded as having histologically proven pancreatic ductal adenocarcinoma (PDAC) and were re- evaluated in a double blind fashion by three pathologists with special expertise in pancreatic pathology. Results: Between 1990 and 1996, the Finnish Cancer Registry recorded 4922 pancreatic cancer patients, 89 of whom survived for at least five years. Reviewing this series of patients revealed 45(49%) non-PDACs and 18 cases without histological verification. In 26 patients recorded as having histologically proven PDAC, re-evaluation of histological specimens confirmed PDAC in only 10 patients. Conclusions: This study indicates that (1) the prognosis of PDAC remains poor and (2) careful histopathological review of all patients with pancreatic cancer is mandatory if survival data are to be meaningful. [ABSTRACT FROM AUTHOR]

To cite this article: Hellgren J, Cervin A, Nordling S, Bergman A, Cardell LO. Allergic rhinitis and the common cold – high cost to society. Allergy 2010; 65: 776–783. Background: The common cold and allergic rhinitis constitute a global health problem that affects social life, sleep, school and work performance and is likely to impose a substantial economic burden on society because of absence from work and reduced working capacity. This study assesses the loss of productivity as a result of both allergic rhinitis and the common cold in the Swedish working population. Methods: Four thousand questionnaires were sent to a randomized adult population, aged 18–65 years, in Sweden, stratified by gender and area of residence (metropolitan area vs rest of the country). The human capital approach was used to assign monetary value to lost productivity in terms of absenteeism (absence from work), presenteeism (reduced working capacity while at work) and caregiver absenteeism (absence from work to take care of a sick child). Results: Thousand two hundred and thirteen individuals responded, response rate 32%. The mean productivity loss was estimated at 5.1 days or € 653 per worker and year, yielding a total productivity loss in Sweden of € 2.7 billion a year. Of the total costs, absenteeism (44%) was the dominant factor, followed by presenteeism (37%) and caregiver absenteeism (19%). Poisson regression analyses revealed that women, people in the 18–29 year age group, and respondents with ‘ doctor-diagnosed asthma’ reported more lost days than the rest of the group. Conclusion: In Sweden, the cost of rhinitis is € 2.7 billion a year in terms of lost productivity. A reduction in lost productivity of 1 day per individual and year would potentially save € 528 million. [ABSTRACT FROM AUTHOR]

Background and aim: Matrix metalloproteinases (MMPs) MMP-2 and MMP-9 can degrade type IV collagen of extracellular matrix and basal membranes. As cyclo-oxygenase-2 (COX-2) has been shown to activate MMPs, creating one of the COX-2-promoted pathways of tumour growth and metastasis, the prognostic role of MMP-2 and MMP-9 in gastric cancer was assessed and their association with COX-2 expression was evaluated. Materials and methods: Samples were collected from 342 consecutive patients operated on for gastric cancer, of which 315 were acceptable for MMP-2, MMP-9 and COX-2 immunohistochemistry. Specimens were stained with specific antibodies, evaluated and categorised by two interpreters, and then correlated with clinical data and survival. Results: Epithelial MMP-2 immunoreactivity was associated with male sex, high stage, advanced penetration depth, non-curative surgery, high COX-2 expression and poor survival. Stromal MMP-2 expression correlated with high stage, intestinal type and non-curative surgery whereas MMP-9 correlated only with intestinal type. Stage, intent of surgery and COX-2 were independent prognostic factors. Conclusions: Epithelial MMP-2 expression in gastric cancer is associated with aggressive forms, COX-2 and poor survival, although MMP-2 was not an independent prognostic factor. In gastric cancer tumour growth is apparently induced by COX-2, and invasion is mediated by MMP-2. [ABSTRACT FROM AUTHOR]

Background: Cyclooxygenase-2 (COX-2) overexpression is related to poor outcome in several cancers. COX-2 is upregulated in 42-90% of pancreatic ductal adenocarcinomas and is a potential target for chemotherapy. Earlier studies have not shown the expression of COX-2 to be a prognostic factor in pancreatic cancer. Objective: To evaluate the prognostic value of COX-2 in a series of patients with pancreatic adenocarcinoma. Methods: 128 patients operated on for pancreatic adenocarcinoma at Helsinki University Central Hospital between 1974 and 1998 provided sections from primary tumours which were immunohistochemically stained with a COX-2-antihuman monoclonal antibody. Results: Cytoplasmic COX-2 reactivity (>5%) occurred in 46 specimens (36%), correlating neither with age, sex, stage, size, tumour stage, nodal metastases, nor grade. Lack of COX-2 expression correlated with distant metastases (p = 0.026). In univariate survival analysis, COX-2 expression (p = .0.014), stage (p = 0.0002), grade (p = 0.0001), and age (p = 0.042) had prognostic significance. One, two, and five year survival rates were 51%, 32%, and 8% in the COX-2 negative groups compared with 34%, 5%, and 5% in the COX-2 positive groups (p = 0.011). Prognostic significance was especially high for patients operated on with curative intent (p = 0.004). In multivariate analysis, COX-2 was an independent prognostic factor (hazard ratio = 1.6 (95% confidence interval, 1.1 to 2.3)). Conclusions: Expression of COX-2 was associated with poor outcome from pancreatic ductal adenocarcinoma and was independent of tumour stage, grade, or age in multivariate analysis. [ABSTRACT FROM AUTHOR]

Wiksten J-P, Lundin J, Nordling S, Kokkola A, Stenman U-H&Haglund C(2005)HistopathologyHigh tissue expression of tumour-associated trypsin inhibitor (TATI) associates with a more favourable prognosis in gastric cancer: The tumour-associated trypsin inhibitor (TATI) is a 6-kDa protease inhibitor with potential inhibitory effects on tissue degradation. In serum, increased levels have been associated with adverse prognosis in different forms of cancer. We assessed the tumour tissue expression and prognostic value of TATI in a surgically treated, single-institution series of patients with gastric cancer.: Using a monoclonal anti-TATI antibody, immunohistochemistry was performed on formalin-fixed paraffin-embedded tumour specimens from 336 patients. TATI expression was observed in 265 (79%) of the tumours. There was a significant association between high TATI expression and low stage (P = 0.007), superficial tumours (P = 0.005), and absence of nodal (P = 0.015) and of distantmetastases (P = 0.022). In univariate analysis, patients with high TATI expression had a significantly more favourable 5-year cumulative survival compared with patients with negative to moderate immunostaining (43% and 28%, respectively,P = 0.006). On multivariate survival analysis stratified for estimated cure of surgery, stage (P < 0.0001) and age (P =0.022) at the time of surgery were independent prognostic factors.: High TATI expression in tumour tissue was detected more frequently in patients with early-stage gastric cancer and seems to correlate with a favourable outcome. [ABSTRACT FROM AUTHOR]

To study cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) expression in papillary thyroid cancer (PTC). Expression of COX-2 is elevated in various human tumours and it has an important role in carcinogenesis. MMP-2 is also an important component of the metastatic potential of tumours. In PTC the most important factor affecting survival is age, but it is poorly understood why older PTC patients have a worse prognosis. Our study shows that COX-2 expression increases with age. It is possible that the age-related increase in COX-2 expression could explain the more aggressive behaviour of PTC in the older age group compared with the young one. [ABSTRACT FROM AUTHOR]

Previous molecular cytogenetic studies by comparative genomic hybridization (CGH) on primary tumours of human malignant mesothelioma have revealed that loss of genetic material at chromosome 14q is one of the most frequently occurring aberrations. Here we further verify the frequency and pattern of deletions at 14q in mesothelioma. A high-resolution deletion mapping analysis of 23 microsatellite markers was performed on 18 primary mesothelioma tumours. Eight of these had previously been analysed by CGH. Loss of heterozygosity or allelic imbalance with at least one marker was detected in ten of 18 tumours (56%). Partial deletions of varying lengths were more common than loss of all informative markers, which occurred in only one tumour. The highest number of tumours with deletions at a specific marker was detected at 14q11.1-q12 with markers D14S283 (five tumours), D14S972 (seven tumours) and D14S64 (five tumours) and at 14q23-q24 with markers D14S258 (five tumours), D14S77 (five tumours) and D14S284 (six tumours). We conclude from these data that genomic deletions at 14q are more common than previously reported in mesothelioma. Furthermore, confirmation of previous CGH results was obtained in all tumours but one. This tumour showed deletions by allelotyping, but did not show any DNA copy number change at 14q by CGH. Although the number of tumours allelotyped was small and the deletion pattern was complex, 14q11.1-q12 and 14q23-q24 were found to be the most involved regions in deletions. These regions provide a good basis for further molecular analyses and may highlight chromosomal locations of tumour suppressor genes that could be important in the tumorigenesis of malignant mesothelioma. [ABSTRACT FROM AUTHOR]

Xanthine oxidoreductase (XOR) is a key enzyme in degradation of DNA and RNA, and has previously been shown to be decreased in aggressive breast and gastric cancer. In this study, XOR expression was assessed in tissue microarray specimens of 478 patients with colorectal cancer and related to clinical parameters. In addition, we performed in vitro studies of XOR activity, protein and mRNA in colon cancer cells (Caco-2). Results from the tissue expression analyses show that XOR was decreased in 62% and undetectable in 22% of the tumours as compared to normal tissue. Loss of XOR was associated with poor grade of differentiation (p=0.006) and advanced Dukes stage (p=0.03). In multivariate survival analysis, XOR was a prognostic factor (p=0.008), independent of Dukes stage, histological grade, age and tumour location. The in vitro analyses show that XOR is not measurable in undifferentiated Caco-2 cells, but appears and increases with differentiation. We conclude that XOR expression is associated with histological grade of differentiation and extent of disease in colorectal cancer, and it provides significant prognostic information independently of established factors. [ABSTRACT FROM AUTHOR]

Objectives To analyze the expression of the androgen receptor(AR) and syndecan-1 in breast tissue during long-term hormonal treatment in cynomolgus monkeys. Methods Sixty oophorectomized macaques were randomized to receive either tibolone, conjugated equine estrogens (CEE), CEE + medroxyprogesterone acetate (MPA) or no hormonal treatment. Breast tissue was collected at necropsy after 2 years and stained for AR and syndecan-1. Results Apparent differences were seen between treatment groups as compared to untreated animals. AR expression was markedly increased by tibolone and suppressed by combined CEE/MPA. Both treatments increased syndecan-1 in stromal tissue, whereas CEE alone had no significant effect. Conclusions We found alternative regimens for hormonal therapy to differ in their influence on two markers of importance for the development of breast cancer. The results may be relevant for the ongoing clinical discussion on the long-term safety of different hormonal treatments. [ABSTRACT FROM AUTHOR]

KIT and PDGFRA are receptor tyrosine kinases that can be specifically inactivated by small-molecule tyrosine kinase inhibitors, notably imatinib mesylate. In ovarian carcinoma, expression of KIT and PDGFRA protein has been documented, but the frequency and the molecular background of expression are poorly known. We analysed the expression of KIT and PDGFRA by immunohistochemistry in 522 serous ovarian carcinomas, and mutations of KIT and PDGFRA by denaturing high-performance liquid chromatographyin 125 and 187 serous ovarian carcinomas, respectively. No mutations of KIT or PDGFRA were detected. KIT expression was detected in 12% of carcinomas: low expression in 10% and high expression in 2% of cases. Using normal serous epithelium as a reference, decreased PDGFRA expression was detected in 12% and increased expression in 13% of carcinomas. Both KIT and PDGFRA expression were associated with high tumour grade, high proliferation index and poor patient outcome. By fluorescence in situ hybridisation, no KIT amplification was found in carcinomas with high KIT expression, but two cases showed a relative gain of chromosome 4. In conclusion, no mutations of KIT or PDGFRA were found, but a subset of serous ovarian carcinoma showed overexpression of the proteins, which was associated with aggressive tumour characteristics. [ABSTRACT FROM AUTHOR]

The bile concentrations of trypsinogen-1, -2 and tumour-associated trypsin-inhibitor (TATI) were determined in 23 patients with benign biliary tract disease, two with biliary tract cancer, and in 15 with pancreatic cancer. We also examined the trypsinogen and TATI expression by immunohistochemistry in tissue specimens from biliary tract cancer and non-neoplastic extrahepatic biliary tract. High levels of trypsinogen-1, trypsinogen-2, and TATI occur in bile of most patients. In contrast to the trypsinogens, the levels of TATI were significantly higher in patients with malignant disease than in those with benign diseases (p=0.04). There was no significant correlation between trypsinogen-2 and amylase (r=0.13, p=0.40), indicating that the occurrence of trypsinogen in bile is not a result of reflux of pancreatic fluid into the bile duct. Immunohistochemically, trypsinogen-2 was detected in five and TATI in 12 out of 15 non-neoplastic biliary tract specimens, and in four and seven out of 11 cholangiocarcinomas, respectively. High concentrations of trypsinogen-1, trypsinogen-2 and TATI occur in the bile of patients with non-neoplastic and malignant biliary tract disease and in patients with pancreatic cancer. At least part of the trypsinogen-2 and TATI found in bile appears to be derived from the biliary epithelium itself. [ABSTRACT FROM AUTHOR]