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Characterization of a MAb to ovarian cancer and its possible diagnostic application.

We report the distribution pattern of the target antigen of an IgG1 monoclonal antibody, Ki-OC III raised in BALB/C mice against solubilised ovarian adenocarcinoma, in normal tissue and in a collection of human tumour types. Special reference was made to benign and malignant ovarian tumours. The reactive antigen protein purified to homogeneity for a planned amino acid analysis showed three bands between 37-40 kDa. Immunohistochemical analysis revealed a specificity of 98% and a sensitivity of 77%. The tracer kinetics of the radiolabelled antibody were tested on a human ovarian carcinoma cell line in athymic mice. The results were compared to cell lines derived from breast and stomach carcinomas as well as to a human glioblastoma cell line. The results show the preferential uptake by ovarian cancer cells followed by breast cancer cell lines. In animal models, scintigraphic monitoring and direct measurement of the radio-labelled monoclonal antibody showed a preferential accumulation in tumours, in addition to high level signals in the liver, kidney, spleen and heart which were related to degradation, excretion and high circulation. The Ki-OC III reactive antigen could be a potential candidate for immunomonitoring of ovarian and possibly also of breast cancer, for in vivo tumour imaging as well as for histopathologic examinations.

Amino Acid Sequence↗

[Differential diagnostic evaluation of chronic pancreatitis in relation to pancreatic cancer based on clinical, laboratory chemical and diagnostic parameters. Studies of 174 patients in 10 years].

174 patients with chronic pancreatic diseases, 30 patients with pancreatic carcinoma and 144 with chronic relapsing pancreatitis, 50 of them with calcifications, were observed in the Department of Internal Medicine of the University of Marburg/FRG between 1972 and 1982. In order to differentiate between carcinoma and relapsing pancreatitis the data of these patients were analysed retrospectively with regard to patient history, actual complaints, findings of laboratory, sonography, ERCP and X-ray investigations. The following results were obtained: Of discriminating value are steatorrhoe, local palpatory pain, alcohol ingestion, a history of earlier attacks and relapsing pain situations; however, general abdominal pain, nausea, vomiting and weight loss (if not exactly specified) are not. Within the laboratory findings bilirubin, GOT, alkaline phosphatase, gamma-GT, serum potassium, blood sugar and chymotrypsin content of the stool were significant while serum and urine amylase were similarly distributed within the groups of patients. Carcinoma and chronic relapsing pancreatitis can be identified by sonography in the majority of patients, but calcifications of the pancreas were rarely demonstrated during this observation period. The obstruction of the extrahepatic bile ducts--mostly due to a carcinoma of the pancreas head--was usually well documented by sonography. Intraabdominal air proofed to be the most disturbing factor. In carcinoma patients, the ERCP is important in demonstrating a complete obstruction of the pancreatic duct and stenosis and dilatation of the extrahepatic bile ducts. In patients with chronic relapsing pancreatitis the pancreatic duct alterations such as dilatations and partial stenosis are well documented by ERCP especially if calcifications occur. In patients without calcifications, dilatation of the branches of the main duct are less relevant in the diagnosis of pancreatic diseases. Radiological demonstration of calcification of the pancreatic area is important for the differential diagnosis. Longstanding characteristical complaints, symptoms and calcifications within the pancreatic area are the most relevant factors in discriminating carcinoma and chronic relapsing pancreatitis.

Adult↗

Diagnostic accuracy in lung cancer; comparison of techniques used in association with flexible fiberoptic bronchoscopy.

Flexible fiberoptic bronchoscopic examination was performed 254 times in 228 patients in a prospective study to determine what specimens would give the greatest yield in the diagnosis of lung cancer. In addition, we questioned whether postbronchoscopic sputum specimens were still the most accurate method of diagnosing lung cancer, as they had been when only the rigid bronchoscope was available. Material for cytopathologic examination was obtained from bronchial brushings, bronchial biopsy, bronchial brushings in saline solution, bronchial washings, and three postbronchoscopie sputum specimens. In the latter part of the study, patients with peripheral tumors were studied with the aid of biplane fluoroscopic techniques. Bronchial brushings and bronchial biopsy each yielded the highest percentage of positive specimens (65 percent); postbronchoscopic sputum specimens were less frequently positive (40 percent). The combination of bronchial brushings and bronchial biopsies gave the optimum overall accuracy (79 percent). Bronchial washings and postbronchoscopic sputum specimens did not add significantly to diagnostic yield, and we conclude that they should no longer be part of the diagnostic procedures routinely ordered. In peripheral lesions, diagnostic accuracy was greatly enhanced in the cases where biplane fluoroscopic techniques were employed.

Biopsy↗

Concomitant analysis of salivary tumor markers--a new diagnostic tool for oral cancer.

PURPOSE: Oral squamous cell carcinoma (OSCC) is a common human malignancy. Circulatory epithelial tumor markers were previously investigated in the serum of OSCC patients but almost never in their saliva, in spite of the fact that there is a direct contact between the saliva and the oral cancer lesion. The purpose of the current study was to examine tumor markers in the saliva of OSCC patients. EXPERIMENTAL DESIGN: We measured the concentrations of the six most studied epithelial serum circulatory tumor markers in the saliva of OSCC (tongue) patients. RESULTS: Significant increases (of 400%) in salivary concentrations of Cyfra 21-1, tissue polypeptide antigen, and CA125 were shown. Salivary concentrations of CA19-9, SCC, and carcinoembryonic antigen were increased without statistical significance. A concurrent analysis of the three significantly increased markers revealed sensitivity, specificity, and negative and positive predictive values of 71%, 75%, 71%, and 75%, respectively. CONCLUSIONS: The increase reported in salivary tumor markers may be used as a diagnostic tool, especially when a concurrent analysis for significantly increased markers is done. Salivary testing is noninvasive, making it an attractive, effective alternative to serum testing, and the possibility of developing home testing kits would further facilitate it as a diagnostic aid, enabling patients to monitor their own health at home and is important for those who live far from their treatment centers and especially for those at risk of developing OSCC.

Adult↗

Diagnostic approach to prostate cancer using total prostate specific antigen-based parameters together.

This prospective study investigated the value of serum total prostate specific antigen (tPSA)-based parameters in the diagnosis of prostate cancer (PCa). Serum tPSA, free to tPSA ratio (f/tPSA), PSA density (PSAD), and PSA transition zone (PSAT) were evaluated in 110 patients with histologically confirmed benign prostate hyperplasia (BPH) and 98 patients with PCa. Once the serum tPSA was elevated (greater than 4 ng/ml) or digital rectal examination (DRE) was suspicious, transrectal ultrasound-guided biopsies were recommended. The tPSA, f/tPSA, PSAD, and PSAT levels were significantly different between the BPH and PCa groups. In patients with a tPSA level of 4.1-9.9 ng/ml or an abnormal DRE finding, only PSAT was found to have discriminating power. The cut-off values were 0.15 for f/tPSA, 0.30 for PSAT, and 0.15 for PSAD. The diagnostic sensitivity of a positive result for one of these parameters in the whole group was 84%, but 75% in patients with a tPSA of 4.1-9.9 ng/ml or an abnormal DRE finding. The diagnostic specificity of positive results for 3 parameters was 92% in the whole group and 93% in patients with a tPSA of 4.1-9.9 ng/ml or an abnormal DRE finding. All parameters were influenced by the histological grades. Histological grades showed a negative correlation (r = -0.56) with f/t PSA and a positive correlation (r = 0.44) with PSAT. No diagnostic marker investigated heretofore was able to rule out or detect early PCa in patients with a PSA level of 4.1-9.9 ng/ml. Using the PSA-based parameters together can be helpful in management of these patients. If all of the PSA-based parameters are negative, biopsy might be postponed; patients who have three positive PSA-based parameters should be biopsied. In case of one or two of the parameters, the patient's age and race should be considered in clinical decision-making.

Aged↗

[Value of diagnostic procedures in pancreatic cancer].

At the Surgical Department of Münster University in-patient treatment was applied to 320 patients for pancreas carcinoma, between 1977 and 1984. These cases were concomitantly studied for informative potentials of computed tomography (CT), sonography (Sono), and endoscopic retrograde cholangiopancreatography (ERCP). CT was performed on 163 patients (50.3 per cent), Sono on 180 (56.3 per cent), and ERCP on 90 (28.1 per cent). Highest sensitivity was recorded from ERCP, with 91.1 per cent of correctly positive diagnoses. CT gave correct positive findings in 70.5 per cent of all cases and Sono in 61.1 per cent. Resection rates were not increased by introduction of these new techniques, but the rate rather stayed at 14.8 per cent. While the period between hospitalisation and operation was slightly reduced, surgical intervention was too late for curative resection in most cases. In some highly advanced cases with distant metastases but absence of symptoms on the basis of CT findings, exploratory laparotomy was abandoned. The new methods have improved diagnostic accuracy rather than prognosis of pancreas carcinoma.

Cholangiopancreatography, Endoscopic Retrograde↗

Impact of UK Colorectal Cancer Screening Pilot on hospital diagnostic services.

OBJECTIVE: To determine the impact of the UK Colorectal Cancer Screening Pilot on hospital services involved in the diagnosis of colorectal cancer (predominantly colonoscopy, double contrast barium enema and pathology). METHODS: Routine data from seven hospitals at two sites within Scotland and England participating in the Pilot were collected on activity levels and waiting times for key hospital services (GI medicine, surgery and radiology), plus questionnaire survey data from hospital consultants. RESULTS: Hospital colonoscopy activity increased by 31 per cent in Scotland and 21 per cent in England due to the investigation of faecal occult blood testing (FOBt) positive subjects. The demand for symptomatic (non-screening) colonoscopy also increased. Pilot-generated activity was less than predicted for barium enema services (maximum 3 per cent increase in service volume) but greater than expected for pathology, with approximately 200 specimens/month generated. Out-patient review of Pilot colonoscopy patients and associated administrative duties added substantially to overall GI service workload, but quantification was limited by the quality of routinely available data. There was a wide discrepancy in colonoscopy waiting times between screened and symptomatic patients, with predominantly longer waits for symptomatic patients: otherwise the quality of colonoscopy services appeared to improve. In any future national screening programme, follow-up of patients with adenomas will result in a further increase of 28 per cent in the number of colonoscopies generated (over and above colonoscopy for FOBt-positive subjects), adding substantially to overall workload. CONCLUSIONS: During the planning of any successful national colorectal cancer screening programme, careful consideration must be given to the wider aspects of workload associated with screening, as well as to the implementation of appropriate hospital data collection systems.

Aged↗

[Cancer of the prostate: current diagnostic aspects].

Presentation of the initial results from a program for early diagnosis of prostate cancer, implemented a year ago at the Urology Unit of the Miguel Servet Hospital with the collaboration of the Region's specialists. All patients attending the Urology services, regardless the pathology, are evaluated when rectal examination is suspicious or the plasma PSA levels are higher than 4 ng/ml. Assessment is made through transrectal ultrasound scanning, with random or ultrasound-directed prostatic biopsy depending on the findings. A total of 83 prostatic biopsies have been analyzed n patients thus selected, presence of prostatic carcinoma becoming apparent in 52 (62.6%), 19 of which have undergone radical prostatectomy. The association suspected rectal examination/increased PSA has produced the higher percentages of diagnostic precision (80%) clearly improving those of rectal examination and PSA alone. The methods for local and nodular staging are analyzed, considering the systematic use of laparoscopic lymphadenectomy and biopsy of seminal vesicles highly useful for higher diagnostic precision in these patients. The diagnostic relevance of prognostic factors in advanced cancer is analyzed, this analysis being mandatory to evaluate the different therapeutic.

Antigens, Neoplasm↗

Gene overexpression in pancreatic adenocarcinoma: diagnostic and therapeutic implications.

Pancreatic cancer is the deadliest of cancers, and effective diagnostic and therapeutic strategies are lacking. Global gene expression profiling holds promise for improved diagnosis and treatment. Knowledge of the location and timing of gene overexpression and the function of these genes, including their effects on signaling pathways, is important. These data may be used to develop histologic and serum biomarkers as well as to develop immunotherapeutic, molecular targeting, and gene therapy strategies. We have compiled a list of overexpressed genes in pancreatic cancer for which overexpression was confirmed by reverse transcriptase polymerase chain reaction, immunohistochemistry, and/or in situ hybridization following initial identification by global gene expression profiling. The techniques used in the determination of overexpression, problems encountered in global gene expression profiling, and the diagnostic and therapeutic implications of overexpression are discussed. The S100 gene family, mesothelin, prostate stem cell antigen, and 14-3-3 sigma, may have important clinical implications in pancreatic cancer diagnosis and treatment.

14-3-3 Proteins↗

Serum tumor marker CYFRA 21-1 in the diagnostics of squamous cell lung cancer--comparison with CEA.

The aim of the study was to test the diagnostic value of serum tumor marker CYFRA 21-1 for squamous cell lung cancer (SQCLC) in comparison with carcinoembryonic antigen (CEA). Ninety-one patients were included in this study: 56 with SQCLC-Group I, 25 with other types of lung cancer-Group II, 10 with benign respiratory tract diseases-Group III. Median CYFRA 21-1 serum concentration (ng/ml) was: in Group I: 4.52 (0.94 - > 16), in Group II: 3.58 (1.72 - > 16), in Group III: 2.05 (0.99-3.41). Median CEA serum concentration (ng/ml) was: in Group I: 4.49 (0.76 - > 20), in Group II: 3.32 (1.17 - > 20), in Group III: 3.09 (1.84-6.37). There was a highly significant difference between the levels of CYFRA 21-1 in Group I and III (p < 0.001), but there was no statistically significant difference between the levels of CEA in Group I and III. Sensitivity of CYFRA 21-1 by the cut-off 3.33 ng/ml in the diagnostics of SQCLC was 0.68, specificity 0.90, positive predictive value 0.91, negative predictive value 0.65. Sensitivity of CEA by cut-off 4.61 ng/ml was 0.5 by the same specificity 0.90. CYFRA 21-1 has high sensitivity, specificity and positive predictive value in the diagnostics of SQCLC. Sensitivity of CYFRA 21-1 is significantly higher than sensitivity of CEA in this setting.

Adult↗

Cytokeratin profiles identify diagnostic signatures in colorectal cancer using multiplex analysis of tissue microarrays.

BACKGROUND AND AIMS: Recent cDNA expression profiling analyses indicate that within specific organ cancers Cytokeratins (CKs) dysregulation may identify subgroups with distinct biological phenotypes. Our objectives in this study were (1) to test whether cytokeratins were also distinct on the protein level, (2) to evaluate these biomarkers in a series of well-characterised CRCs, (3) to apply hierarchical cluster analysis to immunohistochemical data. METHODS: Tissue microarrays (TMA) comprising 468 CRC specimens from 203 patients were constructed to evaluate CK5, CK7, CK8, CK13, CK14, CK16, CK17, CK18, CK19 and CK20. In total, 2919 samples were analyzed. RESULTS: Unsupervised hierarchical clustering discovered subgroups represented by reduced CK8 and CK20 expression, that differed by a shorter patients survival. The evaluation of the specific biomarkers by Kaplan-Meier analysis showed that reduced CK8 expression (p<0.01) was significantly associated with shorter patients' survival, but was not an independent factor correlated with tumour stage (pT), grading (G) and nodal stage (pN). CONCLUSIONS: Reduced coexpression of CK8 and CK20 may indicate an epithelial-mesenchymal transition (EMT) representing an important step in the development of more aggressive CRCs. In addition, multiplex analysis of TMAs together with immunohistochemistry (IHC) supplemented by hierarchical clustering are a useful, promising and very powerful tool for the identification of tumour subgroups with diagnostic and prognostic signatures.

Biomarkers, Tumor↗

Metastatic breast cancer to the bladder: a diagnostic challenge and review of the literature.

Nineteen cases of breast cancer metastatic to the bladder and diagnosed in living patients have been identified in the English literature. Most patients were symptomatic with evidence of disseminated disease at the time of diagnosis. Metastasis usually occurred many years after diagnosis, and the prognosis was poor. The definitive modality for diagnosis in all cases was cystoscopy, which demonstrated an abnormal lesion in the bladder wall that was confirmed on biopsy. In our study, we discuss the case of a patient with breast cancer metastatic to the bladder despite a normal cystoscopic evaluation.

Antineoplastic Combined Chemotherapy Protocols↗

HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues.

To analyze HER2 amplification in a large cohort of diagnostic breast cancer specimens, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed on the same specimens with use of Food and Drug Administration&approved products. Procedures were standardized following the manufacturers' recommendations. Of 116,736 IHC specimens, 20% were positive for HER2. In 16,092 FISH specimens, 22.7% showed HER2 amplification. In the subset of 6556 tissues analyzed with IHC and FISH, however, 59% were positive on IHC and 23.6% were amplified on FISH. The increased frequency of positive test results is skewed by more frequent reflex FISH testing. In general, expression and amplification trended together, with the least amplification (4.1%) seen in IHC-negative cases, 7.4% amplification seen in IHC 1+ cases, 23.3% amplification seen in IHC 2+ cases, and 91.7% amplification seen in IHC 3+ cases. When FISH amplification ratios were stratified, the low FISH ratios (2.0-2.2) were most frequently seen in specimens with negative IHC results, high ratios (>5.0) were seen in IHC 3+ specimens, and intermediate levels of amplification were similar for all levels of IHC. The effect of changing the cutoff point was analyzed: removing cases with a ratio of exactly 2.0 decreased the FISH positivity rate to 22.2% in the combined IHC and FISH cohort. Sequentially moving the cutoff point to 2.2 and 2.5 affected cases at all IHC expression levels. Each change removed approximately 2% from the apparent positivity. This large database provides the distribution frequency of HER2 protein expression and gene amplification in invasive ductal and lobular breast cancer. The relationship between level of HER2 amplification and clinical outcome will require reanalysis of pivotal trial data.

Breast↗

Her-2/neu expression in breast cancer--A comparison of different diagnostic methods.

BACKGROUND: Determination of Her-2/neu overexpression in breast cancer has previously been shown to be of prognostic significance. In this study, Her-2/neu expression in breast cancer was characterised by real-time PCR (RLT-PCR) based LightCycler-HER-2/neu DNA Quantification with immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). MATERIAL AND METHODS: Fifteen specimens of invasive breast cancer - whole tissue sections as well as microdissected tumour cells - were subjected to RLT-PCR. Additionally, IHC and FISH were performed. RESULTS: Her-2/neu overexpression was detected by FISH and by real-time PCR in the same tumours. In contrast, IHC revealed discordant results. CONCLUSION: Determination of Her-2/neu amplification by real-time PCR is a sensitive and specific method with some advantages over FISH. This method is simple and reliable and has the potential of categorizing those tumours with borderline Her-2/neu overexpression as determined by IHC.

Breast Neoplasms↗

[The guidelines for diagnostics and treatment of cervical cancer].

Cervical cancer is one of the most common cancers in women. The purpose of this article is to analyze the main diagnostic and treatment strategies for all stages and recurrences of cervical cancer. The article reviews the epidemiological situation, clinical features, diagnostic procedures for detection of this tumor and for evaluation of the dissemination of the disease, staging criteria, TNM (Tumor, Nodes, Metastases) and FIGO (Federation Internationale de Gynecologie et d'Obstetrique) classification, as well as treatment and prognosis. Surgical treatment (radical type II or III hysterectomy and lymphonodectomy) for early stage I and IIA cervical cancer is the main treatment method. Delivery of adjuvant postoperative radiation therapy or concomitant chemoradiation depends on the prognostic factors (tumor penetration to cervical tissues, lymphovascular invasion, tumor invasion to paracervical tissues, and surgical margins). For treatment of more advanced stages of cervical cancer (IIB, IIIA, IIIB, IVA) concomitant chemoradiation: external beam radiotherapy with chemotherapy and brachytherapy is used. Description of the treatment guidelines for each stage of cervical cancer is given in this article. These guidelines are useful for good treatment practice.

Adult↗

ROC analysis of diagnostic performance utilizing serum antiproteases in cancer patients.

Assessment of the accuracy of diagnostic procedures is made independent of diagnostic criteria by means of a receiver-operating-characteristics (ROC) curve. We performed ROC analysis for the major serum antiproteases: alpha-1-antitrypsin (A1AT) and alpha-2-macroglobulin (A2M), in 99 cancer patients compared with 71 normal individuals. A1AT and A2M were significantly higher in cancer patients (p less than 0.0005). By comparing true positive and false positive rates for different serum levels, ROC analysis showed that serum A1AT quantification seems more useful in clinical practice than serum A2M.

Adult↗

Predictive value of SCC-Ag, CYFRA 21-1 and selected acute phase proteins in radiotherapy of pharyngeal and laryngeal cancer. A preliminary report.

The diagnostic sensitivity and specificity of tumor markers in head and neck cancers is not satisfactory. It is a stimulus for search of other biochemical indicators, among others determinations of acute phase proteins, helpful in head and neck cancers diagnostics and prognosis. In a group of 33 patients with squamous cell carcinoma of the pharynx and larynx (T1-4 N0-3 M0) CYFRA 21-1, SCC-Ag and acute phase proteins such as prealbumin, albumin, alpha-1 acid glycoprotein, alpha-1 antytrypsin, transferrin, ceruloplasmin and C-reactive protein (CRP) determinations were performed before radiotherapy. Significantly greater area under ROC curve for CYFRA 21-1 than for SCC-Ag was found. In T3-4 group, significantly lower albumin and higher AAG and CRP concentrations in comparison with T1-2 patients were observed. Multivariate analysis revealed that apart from tumor stage, elevated concentrations of SCC-Ag and/or CRP are independent unfavorable prognostic factors.

Acute-Phase Proteins↗

The influence of diagnostic radiography on the incidence of breast cancer and leukemia.

Little accurate information is available on the influence of diagnostic radiography on the incidence of cancer in the general population, largely because of a lack of knowledge of the numbers and the age distributions of patients undergoing radiographic examinations. We used such information from a closed population in Maine that was followed for a year, along with data from the literature on the absorbed dose from typical examinations and a mathematical model linking dose to the incidence rate of cancer, to estimate the numbers of cases of radiologically induced cancer of the bone marrow and breast. Our data indicate that about 1 percent of all cases of leukemia and less than 1 percent of all cases of breast cancer result from diagnostic radiography. In addition, such tumors generally occur late in life; the incidence of radiation-induced leukemia was highest at 69 years, and the incidence of radiation-induced breast cancer was highest at 76 years. Thus, diagnostic radiography has only a small influence on the occurrence of leukemia and breast cancer.

Adolescent↗