Postoperative non-steroidal anti-inflammatory drug use and oncological outcomes of rectal cancer.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to suppress the inflammatory response after surgery and are often used for pain control. This study aimed to investigate NSAID use after radical surgical resection for rectal cancer and long-term oncological outcomes. METHODS: A cohort of patients who underwent anterior resection for rectal cancer between 2007 and 2013 in 15 hospitals in Sweden was investigated retrospectively. Data were obtained from the Swedish Colorectal Cancer Registry and medical records; follow-up was undertaken until July 2019. Patients who received NSAID treatment for at least 2 days after surgery were compared with controls who did not, and the primary outcome was recurrence-free survival. Cox regression modelling with confounder adjustment, propensity score matching, and an instrumental variables approach were used; missing data were handled by multiple imputation. RESULTS: The cohort included 1341 patients, 362 (27.0 per cent) of whom received NSAIDs after operation. In analyses using conventional regression and propensity score matching, there was no significant association between postoperative NSAID use and recurrence-free survival (adjusted hazard ratio (HR) 1.02, 0.79 to 1.33). The instrumental variables approach, including individual hospital as the instrumental variable and clinicopathological variables as co-variables, suggested a potential improvement in the NSAID group (HR 0.61, 0.38 to 0.99). CONCLUSION: conventional modelling did not demonstrate an association between postoperative NSAID use and recurrence-free survival in patients with rectal cancer, although an instrumental variables approach suggested a potential benefit.

Surface-protein interactions on different stainless steel grades: effects of protein adsorption, surface changes and metal release.

Implantation using stainless steels (SS) is an example where an understanding of protein-induced metal release from SS is important when assessing potential toxicological risks. Here, the protein-induced metal release was investigated for austenitic (AISI 304, 310, and 316L), ferritic (AISI 430), and duplex (AISI 2205) grades in a phosphate buffered saline (PBS, pH 7.4) solution containing either bovine serum albumin (BSA) or lysozyme (LSZ). The results show that both BSA and LSZ induce a significant enrichment of chromium in the surface oxide of all stainless steel grades. Both proteins induced an enhanced extent of released iron, chromium, nickel and manganese, very significant in the case of BSA (up to 40-fold increase), whereas both proteins reduced the corrosion resistance of SS, with the reverse situation for iron metal (reduced corrosion rates and reduced metal release in the presence of proteins). A full monolayer coverage is necessary to induce the effects observed.

Hemolytic properties of synthetic nano- and porous silica particles: the effect of surface properties and the protection by the plasma corona.

Novel silica materials incorporating nanotechnology are promising materials for biomedical applications, but their novel properties may also bring unforeseen behavior in biological systems. Micro-size silica is well documented to induce hemolysis, but little is known about the hemolytic activities of nanostructured silica materials. In this study, the hemolytic properties of synthetic amorphous silica nanoparticles with primary sizes of 7-14 nm (hydrophilic vs. hydrophobic), 5-15 nm, 20 nm and 50 nm, and model meso/macroporous silica particles with pore diameters of 40 nm and 170 nm are investigated. A crystalline silica sample (0.5-10 µm) is included for benchmarking purposes. Special emphasis is given to investigations of how the temperature and solution complexity (solvent, plasma), as well as the physicochemical properties (such as size, surface charge, hydrophobicity and other surface properties), link to the hemolytic activities of these particles. Results suggests the potential importance of small size and large external surface area, as well as surface charge/structure, in the hemolysis of silica particles. Furthermore, a significant correlation is observed between the hemolytic profile of red blood cells and the cytotoxicity profile of human promyelocytic leukemia cells (HL-60) induced by nano- and porous silica particles, suggesting a potential universal mechanism of action. Importantly, the results generated suggest that the protective effect of plasma towards silica nanoparticle-induced hemolysis as well as cytotoxicity is primarily due to the protein/lipid layer shielding the silica particle surface. These results will assist the rational design of hemocompatible silica particles for biomedical applications.

A web-based prognostic tool for extremity and trunk wall soft tissue sarcomas and its external validation.

BACKGROUND: We developed a web-based, prognostic tool for extremity and trunk wall soft tissue sarcoma to predict 10-year sarcoma-specific survival. External validation was performed. METHODS: Patients referred during 1987-2002 to Helsinki University Central Hospital are included. External validation was obtained from the Lund University Hospital register. Cox proportional hazards models were fitted with the Helsinki data. The previously described model (SIN) includes size, necrosis, and vascular invasion. The extended model (SAM) includes the SIN factors and in addition depth, location, grade, and size on a continuous scale. Models were statistically compared according to accuracy (area under the ROC curve=AUC) of 10-year sarcoma-specific survival prediction. RESULTS: The AUC of the SAM model in 10-year survival prediction in the Helsinki patient series was 0.81 as compared with 0.74 for the SIN model (P=0.0007). The corresponding AUCs in the external validation series were 0.77 for the SAM model and 0.73 for the SIN model (P=0.03). A web-based calculator for the SAM model is available at http://www.prognomics.org/sam. CONCLUSION: Addition of grade, depth, and location as well as tumour size on a continuous scale significantly improved the accuracy of the prognostic model when compared with a model that includes only size, necrosis, and vascular invasion.

Adsorption and protein-induced metal release from chromium metal and stainless steel.

A research effort is undertaken to understand the mechanism of metal release from, e.g., inhaled metal particles or metal implants in the presence of proteins. The effect of protein adsorption on the metal release process from oxidized chromium metal surfaces and stainless steel surfaces was therefore examined by quartz crystal microbalance with energy dissipation monitoring (QCM-D) and graphite furnace atomic absorption spectroscopy (GFAAS). Differently charged and sized proteins, relevant for the inhalation and dermal exposure route were chosen including human and bovine serum albumin (HSA, BSA), mucin (BSM), and lysozyme (LYS). The results show that all proteins have high affinities for chromium and stainless steel (AISI 316) when deposited from solutions at pH 4 and at pH 7.4 where the protein adsorbed amount was very similar. Adsorption of albumin and mucin was substantially higher at pH 4 compared to pH 7.4 with approximately monolayer coverage at pH 7.4, whereas lysozyme adsorbed in multilayers at both investigated pH. The protein-surface interaction was strong since proteins were irreversibly adsorbed with respect to rinsing. Due to the passive nature of chromium and stainless steel (AISI 316) surfaces, very low metal release concentrations from the QCM metal surfaces in the presence of proteins were obtained on the time scale of the adsorption experiment. Therefore, metal release studies from massive metal sheets in contact with protein solutions were carried out in parallel. The presence of proteins increased the extent of metals released for chromium metal and stainless steel grades of different microstructure and alloy content, all with passive chromium(III)-rich surface oxides, such as QCM (AISI 316), ferritic (AISI 430), austentic (AISI 304, 316L), and duplex (LDX 2205).

Systematic knockdown of epigenetic enzymes identifies a novel histone demethylase PHF8 overexpressed in prostate cancer with an impact on cell proliferation, migration and invasion.

Our understanding of key epigenetic regulators involved in specific biological processes and cancers is still incomplete, despite great progress in genome-wide studies of the epigenome. Here, we carried out a systematic, genome-wide analysis of the functional significance of 615 epigenetic proteins in prostate cancer (PrCa) cells. We used the high-content cell-spot microarray technology and siRNA silencing of PrCa cell lines for functional screening of cell proliferation, survival, androgen receptor (AR) expression, histone methylation and acetylation. Our study highlights subsets of epigenetic enzymes influencing different cancer cell phenotypes. Plant homeo domain (PHD) finger proteins have a key role in cell survival and histone methylation, whereas histone deacetylases were primarily involved in regulating AR expression. In contrast, JumonjiC-domain (JmjC) containing histone lysine demethylases (KDMs) mainly had an impact on cell proliferation. Our results show that the KDMs JARID1B, PHF8, KDM3A, KDM3B and KDM4A were highly expressed in clinical PrCa samples. The PHD-finger protein 8 (PHF8), a transcriptional coactivator with both PHD- and JmjC-domains, was moderately to strongly expressed in 80% of clinical PrCa samples, whereas 76% of normal and benign samples were negative or only showed weak PHF8 expression. Strong PHF8 expression correlated significantly with high Gleason grade and was borderline significant for poor prognosis. The results of functional PHF8 knockdown implicate a role in cell migration and invasion, as shown by cell motility and 3-D invasion assays. Our study suggests that various cellular phenotypes are regulated by distinct subsets of epigenetic enzymes. Proteins interpreting and modifying histone methylation, such as JmjC-domain and particularly PHD-finger proteins like PHF8, are activated in subsets of PrCa's and promote cancer relevant phenotypes.

Expression and prognostic value of transcription factor PROX1 in colorectal cancer.

BACKGROUND: PROX1 is a specific target of the ß-catenin/TCF pathway in the intestinal epithelium. It acts as a regulator of progression from a benign to a highly dysplastic phenotype in colorectal tumours. However, the clinical significance of PROX1 expression is not known. METHODS: We studied the prognostic value of immunohistochemical expression of PROX1 in a series of 517 patients with colorectal cancer (CRC). RESULTS: The majority of the tumour samples expressed PROX1 (91%, 471 out of 517). High PROX1 expression was associated with a poor grade of tumour differentiation (P<0.0001). In the subgroup of patients with colon cancer, high PROX1 expression was associated with unfavourable colorectal cancer-specific survival (CCSS) as compared with low PROX1 expression (CCSS 47% vs 62%; P=0.045; RR 1.47). The association between high PROX1 and poor outcome was further strengthened in female colon cancer patients (CCSS 38% vs 63%; P=0.007; RR 2.02). Nonetheless, in multivariate survival analysis PROX1 expression was not retained as an independent prognostic factor. CONCLUSION: High PROX1 expression is associated with a poor grade of tumour differentiation, and, in colon cancer patients, also with less favourable patient outcome. Our results strengthen the previous preclinical observations that PROX1 has a role in tumour progression in CRC.

A public-domain image processing tool for automated quantification of fluorescence in situ hybridisation signals.

AIMS: To develop and evaluate an automated method for quantification of HER2 fluorescence in situ hybridisation (FISH) signals. METHODS: Using a popular, open source image manipulation tool, ImageJ, a macro for FISH signal assessment was created. A comparison against traditional manual counting was performed in breast cancer specimens from 42 patients. The tumour specimens were hybridised with probes for HER2 and chromosome 17 centromere (CEP17) and selected areas were digitised for image processing. Hybridisation signals were calculated both manually and automatically with the ImageJ custom macro. RESULTS: The correlation coefficient between the automatic and manual HER2/CEP17 ratios was 0.98. The corresponding percentage agreement was 90% and the kappa value was 0.82. CONCLUSIONS: This study shows that it is possible to automate the determination of HER2 amplification by the use of open-source software, with results comparable to manual counting. The automated counting decreases the time needed for sample analysis and provides possibilities to enhance inter- and intralaboratory reproducibility of results. The FISH quantification tool (FishJ) is available for download as an ImageJ macro or alternatively it can be utilised through a web interface with an option of uploading FISH images for hybridisation signal counting. Combined with digitisation of FISH samples, the FishJ macro enables gene copy number to be assessed and re-evaluated on any area of a digitised specimen.

Tenascin-C expression and its prognostic significance in colorectal cancer.

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.

Decreased xanthine oxidoreductase is a predictor of poor prognosis in early-stage gastric cancer.

BACKGROUND: Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA and high-energy phosphates. About half of the patients with breast cancer have a decrease in XOR expression. Patients with breast cancer with unfavourable prognosis are independently identified by the loss of XOR. AIM: To assess the clinical relevance of XOR expression in gastric cancer. METHODS: XOR levels were studied by immunohistochemistry in tissue microarray specimens of 337 patients with gastric cancer and the relation between XOR expression and a series of clinicopathological variables, as well as disease-specific survival, was assessed. RESULTS: XOR was moderately decreased in 41% and was undetectable in another 14% of the tumours compared with the corresponding normal tissue. Decreased XOR was associated with advanced stage, deep tumour penetration, diffusely spread tumour location, positive lymph node status, large tumour size, non-curative disease, cellular aneuploidy, high S-phase fraction and high cyclooxygenase-2 expression, but not with p53 expression or Borrmann classification. Down regulation of XOR was associated with unfavourable outcome, and the cumulative 5-year gastric cancer-specific survival in patients with strong XOR expression was 47%, compared with 22% in those with moderate to negative expression (p<0.001). This was also true in patients with stage I-II (p = 0.01) and lymph node-negative (p = 0.02) disease, as well as in patients with smaller (< or =5 cm) tumours (p = 0.02). CONCLUSION: XOR expression in gastric cancer may be a new marker for a more aggressive gastric cancer biology, similar to that previously reported for breast cancer.

Epithelial syndecan-1 expression is associated with stage and grade in colorectal cancer.

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.

A digital atlas of breast histopathology: an application of web based virtual microscopy.

AIMS: To develop an educationally useful atlas of breast histopathology, using advanced web based virtual microscopy technology. METHODS: By using a robotic microscope and software adopted and modified from the aerial and satellite imaging industry, a virtual microscopy system was developed that allows fully automated slide scanning and image distribution via the internet. More than 150 slides were scanned at high resolution with an oil immersion x 40 objective (numerical aperture, 1.3) and archived on an image server residing in a high speed university network. RESULTS: A publicly available website was constructed, http://www.webmicroscope.net/breastatlas, which features a comprehensive virtual slide atlas of breast histopathology according to the World Health Organisation 2003 classification. Users can view any part of an entire specimen at any magnification within a standard web browser. The virtual slides are supplemented with concise textual descriptions, but can also be viewed without diagnostic information for self assessment of histopathology skills. CONCLUSIONS: Using the technology described here, it is feasible to develop clinically and educationally useful virtual microscopy applications. Web based virtual microscopy will probably become widely used at all levels in pathology teaching.

Photoneutron yields from tungsten in the energy range of the giant dipole resonance.

Photoneutron production on the nuclei of high-Z components of medical accelerator heads can lead to a significant secondary dose during a course of bremsstrahlung radiotherapy. However, a quantitative evaluation of secondary neutron dose requires improved data on the photoreaction yields. These have been measured as a function of photon energy, neutron energy and neutron angle for natW, using tagged photons at the MAX-Lab photonuclear facility in Sweden. This work presents neutron yields for natW(gamma, n) and compares these with the predictions of the Monte Carlo code MCNP-GN, developed specifically to simulate photoneutron production at medical accelerators.

Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer.

The prognostic value of the immunohistochemical expression of epithelial and stromal syndecan-1 was evaluated in 296 patients with gastric carcinoma. Formalin-fixed, paraffin-embedded specimens of gastric adenocarcinomas were stained with mouse monoclonal antibody B-B4 against human syndecan-1. Loss of immunoreactivity (syndecan-1 immunoreactivity correlated with a higher stage of disease (stages II-IV), tumour location in the upper third of the stomach, nodal metastases (N1 or N2), positive stromal syndecan-1 staining, deep tumour penetration (to subserosa or deeper = T2-T4), larger tumour size (> or = 5 cm) and intestinal type of cancer. No correlation between epithelial syndecan-1 immunoreactivity and age, gender, distant metastases, grade of differentiation or Borrmann classification was observed. Positive stromal syndecan-1 immunoreactivity correlated with decreased epithelial syndecan-1 expression, intestinal type of cancer and Borrmann type I. Patients with low epithelial syndecan-1 expression in cancer cells had worse overall survival than patients with strong epithelial syndecan-1 staining (p = 0.0012). Stromal syndecan-1-positive patients had a worse outcome than patients with syndecan-1-negative stroma (p = 0.0193). In Cox multivariate analysis, stromal syndecan-1 immunoreactivity was a prognostic factor independent of TNM stage, surgery for cure and tumour size. Thus, the immunohistochemical expression of syndecan-1 might be a predictor of outcome in patients with gastric adenocarcinoma.

Tissue expression of human chorionic gonadotropin beta predicts outcome in colorectal cancer: a comparison with serum expression.

Production of the glycoprotein hormone human chorionic gonadotropin beta (hCGbeta) has been associated with more aggressive behavior in non-trophoblastic tumors. In this study, the prognostic value of immunohistochemical hCGbeta expression was evaluated in 239 patients with colorectal cancer. Paraffin-embedded, formalin-fixed specimens were stained with hCGbeta-specific monoclonal antibody, and the results were compared with serum levels determined with an assay based on the same antibody. hCGbeta immunoreactivity was seen in 52 of 239 tumors (22%). The difference in survival time between patients with histologically hCGbeta-negative (median survival 94 months) and -positive (median survival 27 months) tumors was statistically significant (p = 0.014). The risk ratio during follow-up for patients with positive hCGbeta tissue expression was 1.65 (95% CI 1.11-2.46). In a Cox multivariate analysis, Dukes' stage, hCGbeta and age remained independent prognostic factors. There was moderate agreement between immunohistochemical and serum expression levels of hCGbeta (kappa = 0.30). Using a combination of histological and serum levels of hCGbeta, the difference between survival rates was highly significant (p < 0.001). The accuracy when predicting 5-year survival status with the combined results of serum and tissue expression was 1.3% higher compared to hCGbeta tissue expression alone. Our results show that hCGbeta expression in both tumor tissue and serum has prognostic significance independent of other clinicopathological variables. Positive tumor staining does not always occur together with elevated serum levels, and the prognostic accuracy can slightly be increased by combining the results.

Omission of histologic grading from clinical decision making may result in overuse of adjuvant therapies in breast cancer: results from a nationwide study.

PURPOSE: To investigate the influence of routinely performed histologic grading on breast cancer outcome prediction and patient selection for adjuvant therapy. PATIENTS AND METHODS: The analysis is based on a cohort of 2,842 women diagnosed with breast cancer and comprising 91% of all breast cancers diagnosed in five defined geographical regions in Finland in 1991 through 1992. Data on clinicopathologic factors and follow-up were collected from hospital case records and national registries. Histologic grade assessed at diagnosis and other clinicopathologic data were available for 1,554 operable unilateral invasive carcinomas. The relative value of grade with respect to competing prognostic factors was estimated with the Cox proportional hazards model and logistic regression. Interactions and nonlinearity of factors were accounted for by using an artificial neural network. RESULTS: Histologic grade was correlated strongly with survival in the entire series and in all subgroups studied. Women with well-differentiated node-negative cancer had a 97% 5-year distant disease-free survival rate as compared with 78% for women with poorly differentiated cancer. Grade was an independent prognostic factor in multivariate models and increased the predictive accuracy of a neural network model. Inclusion of grade data in a Cox multivariate model based on tumor size and hormone receptor status in node-negative cancer increased the proportion of patients with 5% or less risk for distant recurrence at 5 years from 15% to 54%. CONCLUSION: Even when assessed by pathologists who have no special training in breast cancer pathology, histologic grade has substantial and independent prognostic value in breast cancer. Omission of grading from clinical decision making may result in considerable overuse of adjuvant therapies.

Gene Structure of the U2 snRNP-Specific A' Protein Gene from Salmo salar: Alternative Transcripts Observed.

The genomic sequence of the Atlantic salmon (Salmo salar) U2 snRNP-specific A' protein gene (U2A') was identified on a cosmid clone, and the exon/intron organization of a U2A' gene is described for the first time. The cosmid sequence includes 8 exons from which the 227 amino-terminal amino acids, of a total of 339 amino acids, are deduced. The cosmid cloning site was found in the 8th intron, which also contains a BglII minisatellite repeat region of unknown length. The 3' end of the gene was determined from a complementary DNA sequence. In the 234 amino-terminal amino acids the sequence identity is 84% to human and 49% to Arabidopsis thaliana. The phases of introns 1 to 8 are 1, 2, 0, 2, 0, 2, 0, and 1, respectively. The salmon U2A' gene was found by reverse transcription-polymerase chain reaction to be expressed in all 10 tissues tested, and in addition to the expected fragment of 695 bp, a smaller fragment of 615 bp was amplified in all tissues. Nucleotide sequencing of the fragments obtained showed that the smaller transcript lacks exon 6 and this results in frameshift of exon 7 and a truncated deduced polypeptide. This result may be explained by alternative splicing of the salmon U2A' gene. Different U2A' transcripts were found to exist also in human tissue.

A comparison of serum and tissue hCG beta as prognostic markers in colorectal cancer.

BACKGROUND: Production of the glycoprotein hormone hCG beta has been associated with aggressive behavior in nontrophoblastic tumors. In this study the prognostic value of serum level and tissue expression of hCG beta were compared in 232 patients with colorectal cancer. MATERIALS AND METHODS: Serum levels were measured with a hCG beta specific immunofluorometric assay. Tissue specimens were stained with the same monoclonal antibody as in the serum assay. RESULTS: The proportion of patients with a positive immunohistochemical expression of hCG beta was higher (22%) than the proportion with elevated serum levels (17%). The correlation between serum and tissue expression was moderate (kappa 0.298). Both serum and tissue expression of hCG beta were independent prognostic factors. hCG beta serum level was a stronger prognostic factor than tissue expression both in uni- and in multivariate analysis. The accuracy when predicting 5-year survival status of the patients was highest (63%) when using the combined results of serum and tissue expression. CONCLUSIONS: There is a moderate correlation between hCG beta expression in serum and in tissue. The predictive accuracy of serum hCG beta was higher than the predictive accuracy of tissue expression, and the prognostic accuracy was further slightly increased when using a combination of tissue and serum expression.

Artificial neural networks applied to survival prediction in breast cancer.

In this study, we evaluated the accuracy of a neural network in predicting 5-, 10- and 15-year breast-cancer-specific survival. A series of 951 breast cancer patients was divided into a training set of 651 and a validation set of 300 patients. Eight variables were entered as input to the network: tumor size, axillary nodal status, histological type, mitotic count, nuclear pleomorphism, tubule formation, tumor necrosis and age. The area under the ROC curve (AUC) was used as a measure of accuracy of the prediction models in generating survival estimates for the patients in the independent validation set. The AUC values of the neural network models for 5-, 10- and 15-year breast-cancer-specific survival were 0.909, 0.886 and 0.883, respectively. The corresponding AUC values for logistic regression were 0.897, 0.862 and 0.858. Axillary lymph node status (N0 vs. N+) predicted 5-year survival with a specificity of 71% and a sensitivity of 77%. The sensitivity of the neural network model was 91% at this specificity level. The rate of false predictions at 5 years was 82/300 for nodal status and 40/300 for the neural network. When nodal status was excluded from the neural network model, the rate of false predictions increased only to 49/300 (AUC 0. 877). An artificial neural network is very accurate in the 5-, 10- and 15-year breast-cancer-specific survival prediction. The consistently high accuracy over time and the good predictive performance of a network trained without information on nodal status demonstrate that neural networks can be important tools for cancer survival prediction.

Sialyl Tn is a frequently expressed antigen in colorectal cancer: No correlation with patient prognosis.

Immunohistochemical expression of sialyl Tn antigen (STn), previously claimed to be a prognostic factor in colorectal cancer, was evaluated in 239 patients with colorectal adenocarcinoma. Formalin-fixed, paraffin-embedded specimens were stained with the monoclonal antibody C1282. STn immunoreactivity was seen in 189 of 239 tumors (79%). There was no significant correlation between STn immunoreactivity and Dukes stage, tumor location, histological type or gender. However, STn was significantly more often expressed in younger patients. There was so significant difference in survival between STn-negative patients (median survival 68 months) and STn-positive patients (median survival 79 months). In a Cox multivariate analysis, Dukes stage was the strongest predictor of outcome, followed by the age of the patient, whereas STn did not provide any prognostic information.