bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunocytochemical determination of the tumor-associated glycoproteins MCA, CA 125 and BW 495/36-P in urine of patients with epithelial tumors of the kidney and urinary bladder
Authors: Ammon A. , Weber M.H. , Wallner I. , Marschner N. , Droese M. , Gröne H.J. , Hiddemann W.
Published: March 2018

Pre-operative and, in some cases, post-operative urine samples from 29 patients with renal cell or urinary bladder carcinoma were compared to samples from 24 healthy persons and 10 patients with nephrolithiasis and 9 patients with other benign disorders of the efferent urinary tract. The specimens were examined for the presence of MCA, CA 125 and BW 495/36-P expressing epithelial cells. The urine concentrations of the soluble antigens MCA and CA 125 were determined simultaneously in urine samples from 35 patients with renal cell or urinary bladder carcinoma, 10 patients with cystitis and 30 healthy individuals.

MCA and BW 495/36-P expressing epithelial cells were significantly increased in all pre-operative urine samples of the tumor patients compared to the group of healthy persons. This increase was also seen with CA 125-positive cells in patients with bladder carcinoma, not however in patients with renal cell carcinoma. BW 495/36-P positive cells were also found in both groups of tumor patients in greater numbers than in the patients with nephrolithiasis or other benign urinary tract disorders. Based on a specificity of 97% when compared to the control urine samples, the cytological determination of the antigens MCA, CA 125 and BW 495/36-P in urinary tract cells of all tumor patients revealed a sensitivity of 48%, 33% and 79% as well as a positive predictive value of 92%, 89% and 95%, respectively. The sensitivity of CA 125 increased to 67% upon isolated analysis of patients with bladder carcinoma.

The majority of labelled cells were not identifiable as tumor cells morphologically and appeared as normal transitional epithelial cells.

The urinary concentration of soluble MCA was greatest in healthy patients whereas the concentration of CA 125 was increased in patients with bladder carcinoma.

Our results indicate that especially the determination of BW 495/36-P expressing epithelial cells could be a helpful supplement to the cytological examination of urinary epithelium with regard to renal cell and bladder carcinoma. Determination of CA 125-positive cells appears to be of diagnostic relevance only in cases of suspected bladder carcinoma.
The clinical value of CEA and CA 15-3 in breast cancer management
Authors: Coveney E.C. , Geraghty J.G. , Sherry F. , McDermott E.W. , Fennelly J.J. , O'higgins N.J. , Duffy M.J.
Published: March 2018

The value of tumour-associated antigens CEA and CA 15-3 was studied in patients with breast cancer over a 4-year period. A total of 252 patients with primary or recurrent disease had available and corresponding CEA and CA 15-3 values at diagnosis and during follow-up and were studied in detail. Preoperative and three-monthly serial postoperative levels were measured in each patient. Ten of 11 patients presenting with primary and concurrent metastatic disease had elevated CA 15-3 levels (> 25 I.U./ml) as compared to 6 with CEA (> 5 ng/ml). Fourty-seven patients developed locoregional recurrence of which 15 had concurrent metastatic disease. CA 15-3 was elevated in 14 cases while CEA in 11. Of 32 patients with locoregional recurrence alone, 18 later developed metastatic disease at a mean follow-up time of 17.5 months. There was a significant correlation between CA 15-3 value at locoregional recurrence and time to subsequent metastasis (r = 0. -0.57, P = 0.0133). CEA was elevated in 64%, CA 15-3 in 87% and either marker in 94% of 87 patients diagnosed with metastatic disease. Of 53 patients with serial markers and metastatic disease, 72% (38/53) had rising CA 15-3 levels prior to diagnosis with a mean lead time of 9.9 months. Use of CEA in conjunction improved lead time detection to 83%.

This study demonstrates that CA 15-3 is superior to CEA at detecting metastatic disease at initial presentation and during follow-up. Use of CEA in conjunction with CA 15-3 improves the detection of systemic disease.
Skeletal alkaline phosphatase as a serum marker of bone metastases in the follow-up of patients with breast cancer
Authors: Reale M.G. , Santini D. , Marchei G.G. , Manna A. , Del Nero A. , Bianco V. , Marchei P. , Frati L.
Published: March 2018

Immunoradiometric determination of the bone isoenzyme of alkaline phosphatase with a method provided by Hybritech Inc., San Diego CA (USA) was carried out in 145 female patients, 97 of whom with radically operated breast cancer and 48 with benign mammary cysts, in order to evaluate the correlation of serum levels with the metabolic process of bone rearrangement in patients with bone metastases.

This study shows that skeletal ALP, having high specificity (86.48%) and sensitivity (78.6%) for early progression (the average anticipation time compared to scintigraphic detection was 101 days) could represent a valid marker for bone metastases in association with mucinous markers in the follow-up of patients operated for breast cancer. In addition, dynamic serum determination of skeletal ALP could be a valid help in monitoring the efficacy of therapy in patients with bone progression.
Serum soluble interleukin-2 receptors in epithelial ovarian cancer patients
Authors: Pavlidis N.A. , Bairaktari E. , Kalef-Ezra J. , Nicolaides C. , Seferiadis C. , Fountzilas G.
Published: March 2018

The levels of soluble interleukin-2 receptors (sIL-R2) were measured in the serum of 52 patients with epithelial ovarian carcinoma as well as in 25 age and sex-matched normal controls. The mean serum level of sIL-2R was increased in 37 patients (71.2%). Comparison of these levels to those of normal controls showed a highly statistically significant difference (p<0.001). Serum sIL-2R levels were not related to histology, clinical stage or the presence of ascites (p-0.58, p=0.32 and p=0.67, respectively), nor did they follow disease activity or response to chemotherapy. However, patients with higher pretreatment sIL-2R levels (more than 1200 U/ml) were found to have a longer survival (p<0.02), possibly explained by the presence of activated lymphocytes and a better immune surveillance. We conclude that the serum level of sIL-2R: a) is elevated in ovarian cancer patients, b) has no relationship with histological subtypes, tumor burden or the presence of ascites, c) cannot serve as a valuable tumor marker for the monitoring of patient treatment, and d) has a prognostic value for survival.
Comparison of CA 72-4, CA 19-9 and CEA in the diagnosis and monitoring of gastric cancer
Authors: Safi F. , Kuhns V. , Beger H.G.
Published: March 2018

In order to assess the utility of the tumor-associated antigen CA 72-4 in the diagnosis and monitoring of gastric cancer, this tumor marker was measured preoperatively in 718 patients. This group comprised 282 patients with malignant disease (115 with gastric cancer and 167 with other malig-nancies not involving the stomach) and 476 patients with benign surgical diseases. The results were compared with those for carcinoembryonic antigen (CEA) and the tumor-associated antigen CA 19-9. CA 72-4 was above the normal limit of 2.5 U/ml in 61% of the patients with gastric cancer, in 35% of the patients with other malignancies, and in 7% of the patients with benign diseases. CEA and CA 19-9 were elevated in 37% of the patients with gastric cancer (>3 ng/mlfor CEA and >37 U/ml for CA 19-9). CA 72-4 levels were above 10 U/ml in 26% of the gastric cancer patients, in 15% of patients with other malignancies, and in 0.4% of the patients with benign diseases. There was a good correlation between CA 72-4 level and tumor stage in gastric cancer. CA 72-4 serum levels were over 2.5 U/ml in 31%, 48%, 68% and 88% of patients with stage I, II, III and IV disease, respectively. CA 72-4 was found to be more sensitive than CEA and CA 19-9 in detecting recurrences of gastric cancer. In the postoperative-care period, carcinoma recurred in 29 patients. Of these 93% had CA 72-4 concentrations above 2.5 U/ml, whereas only 59% and 35% had pathological CEA and CA 19-9 serum levels (p<0.002, p<0.0001). Although neither CA 72-4 nor CEA and CA 19-9 are sensitive enough for screening and diagnosis of early gastric cancer, CA 72-4 is superior to CEA and CA 19-9 in the detection of gastric cancer recurrences.
Determination of tissue polypeptide-specific antigen in pleural fluid and serum from patients with pleural effusion
Authors: Villena V. , Echave-Sustaeta J. , Lopez-Encuentra A. , Martin-Escribano P. , Estenoz-Alfaro J. , Ortuño-De-Solo B.
Published: March 2018

As a tool for differentiating malignant and benign pleural effusions, we evaluated the diagnostic value of the assay of tissue polypeptide-specific antigen (TPS) in pleural fluid and serum, and of the pleural fluid TPS/serum TPS ratio in patients with pleural effusion. We studied prospectively 147 consecutive patients who had pleural effusions: 43 malignant pleural effusions and 104 benign pleural effusions. TPS levels were measured by RIA. The sensitivity and specificity of these measurements were: TPS in pleural fluid (cutoff 20,000 U/L): 0.21 and 0.98; TPS in serum (cutoff 300 U/L): 0.31 and 0.96; pleural fluid TPSI serum TPS ratio (cutoff 1200): 0.07 and 0.99.

All these values enhanced the sensitivity of cytologic analysis of pleural fluid. However, we conclude that TPS assay in pleural fluid and serum, and the pleural fluid TPSI serum TPS ratio have limited diagnostic value in patients with pleural effusion.
Development of a new Prolifigen TPA IRMA assay using monoclonal anti-cytokeratin antibodies
Authors: Sundström B. E. , D'amico Y. , Brundell J.
Published: March 2018

A new immunoassay for TPA determination has been developed in which anti-cytokeratin monoclonal antibodies are used. A three-MAb combination with different anti-cytokeratin antibody specificities has been selected to mimic the complex pattern found for the polyclonal anti-TPA antibody. The accuracy of the assay is good, as judged from analytical recovery experiments, analysis of quality-assessment samples and comparison with the polyclonal Prolifigen TPA IRMA. No significant interferences or cross-reactivities have been identified. The lower limit of detection of the assay (mean + 3 SD of the zero standard) is below 15 U/L and the imprecision in low, giving a working range of 15-4000 UIL.

The improved handling of the assay, including a single incubation step of 2 hours with shaking at room temperature, results in a narrower normal distribution, thereby giving a better separation of normal and pathological samples.
Analysis of the Temporal Compressibility of Breast Tumour Marker Assays: Development of a “Near Patient” Assay
Authors: Murray A. , Robertson J. F. R. , Price M. R.
Published: March 2018

The aim of this study was to investigate whether immunoassays for circulating MUC1 antigen in breast cancer could be compressed in time so that serum level results would be made available during the time of the patient's visit to clinic.

Two assays were used: - The EMCA (Euro DPC) is a liquid phase immunoassay and the ELSA CA15-3 (CIS) is a double determinant solid phase immunoradiometric assay. The effects of shortened incubation times were investigated by assaying standards and unknown samples and comparing the results with those using the standard kit protocols. The binding kinetics of the monoclonal antibodies employed in the assays were analysed separately.

We conclude that the EMCA assay can be shortened to 35 min and we have attributed this to the fast binding kinetics inherent in a liquid phase assay. This shortened assay may produce the basis for a useful “near patient” assay. By comparison, the solid phase ELSA CA15-3 assay cannot be compressed without loss in assay performance.
Immunosuppressive Factors: Role in Cancer Development and Progression
Authors: Botti C. , Seregni E. , Ferrari L. , Martinetti A. , Bombardieri E.
Published: March 2018

The concept of the immunological surveillance against neoplastic cells was initially proposed by Erlich in 1909 and later elaborated by Burnet. This hypothesis states that the normal function of the immune system, in particular the cell-mediated immunity, is to recognize and destroy the transformed and proliferating tumor cells. The role of cell-mediated immunity during the first steps of tumorigenesis remains controversial. However, there is certain evidence about its importance in the progression and dissemination of cancer. The frequent immunosuppressed condition of cancer patients at tumor relapse or recurrence of secondary tumors is a clinical sign supporting this hypothesis, and many studies have demonstrated a defective immune response in patients diagnosed with advanced cancer. Several mechanisms of escape from the immune surveillance have been described, including the immunoselection of tumor antigen-negative variants, the downregulation of MHC class I expression, suppressive T cells, and the elaboration of immunosuppressive cytokines and other factors. Because of the technical difficulty of isolating the very small amounts from culture supernatants or body fluids, only a few of these substances have been characterized and studied with respect to their biological activity: transforming growth factor-β (TGF-β), the protein p15E, interleukin 10 (IL-10), prostaglandin E2 (PGE2), mucins, suppressive E-receptor (SER), immunosuppressive acidic protein (IAP), and adhesion molecules. The possibility of monitoring cancer patients by testing biochemical factors related to cancer growth led to a proposal to measure a number of these factors as tumor markers. Some of them, e.g mucins, enjoy the consensus of the oncologic community, as for some indications they can help the clinician in the management of cancer patients. Except for the class of mucins, the other above-mentioned immunosuppressive factors have not found any clinical application in the laboratory routine because the information deriving from their measurement, although of speculative and scientific interest, has limited clinical value at present. Nevertheless, even if they have no impact on patient management, these substances do have a potential role to play in the study of cancer patients, and should be taken into account when developing new therapeutic strategies.
The Value of Pretreatment Clinical and Biochemical Parameters in Staging and Prognostic Stratification of Patients with Newly Diagnosed Prostate Carcinoma
Authors: Stokkel M.P.M. , Zwinderman A. H. , Zwartendijk J. , Pauwels E.K.J. , Van Eck-Smit B.L.F.
Published: March 2018

Purpose

To determine whether it is possible to select patients in whom and for what reason bone scintigraphy should be performed or not, a retrospective study was performed of 161 consecutive patients with newly diagnosed prostate cancer.

Materials and methods

Follow-up varied from 1 to 88 months during which 67 patients died. Bone scans were classified from 0 (= normal) to 3 (typical pattern of metastases) and were correlated with age, alkaline phosphatase (AP), prostate specific antigen (PSA), tumor grade, TNM-stage and survival. For survival, 68 patients who were not referred for bone scintigraphy were also evaluated.

Results

All parameters demonstrated a correlation with the incidence of a positive bone scan, but PSA was the best overall predictor in this (p<0.0001). None of the patients with PSA ≤ 20 ng/ml (n=64) showed metastases, whereas 8 of 9 patients with PSA > 1000 ng/ml and patients with PSA values between 20 and 1000 ng/ml in combination with AP >90 U/L (n=24) had bone metastases. Furthermore, a class 3 bone scan was found to be the most important parameter in assessing prognosis and survival (p<0.0001), whereas no differences were found in patients with a class 0, 1 and 2 scintigram.

Conclusions

For staging and prognostic stratification purposes, bone scintigraphy and additional roentgenograms are of value in a selected group of patients. In contrast with a typical pattern of metastases on bone scintigraphy, an abnormal scan (class 1 and 2) at the time of diagnosis is not a poor prognostic parameter of the risk of death. Bone scintigraphy can be omitted in patients with PSA values < 20 ng/ml. In patients with PSA levels > 1000 ng/ml or less increased levels combined with alkaline phosphatase levels > 90 U/L, bone scintigraphy seems to be of no value in staging disease.
Urinary Excretion of Free and Acetylated Polyamines in Hepatocellular Carcinoma
Authors: Antoniello S. , Auletta M. , Magri P. , Pardo F.
Published: March 2018

Polyamines (putrescine, spermidine and spermine) are essential for the proliferation of normal and neoplastic cells, and have been repeatedly recommended as tumor markers, with contrasting and elusive results.

In the present study the urinary excretion of free and acetylated polyamines was measured in patients with hepatocellular carcinoma (HCC), cirrhotics and control subjects.

Separation and quantification of dansyl-derivatives of free, acetylated and total polyamines was performed by reverse-phase high-performance liquid chromatography.

The results show that the urinary excretion of total, free, and acetylated polyamines is significantly higher in HCC patients than in cirrhotics and controls (p<0.001). The N1/N8 acetyl-spermidine molar ratio was found to be higher in HCC patients than in cirrhotics and controls (p<0.001). No correlation was found between urinary excretion of polyamines and serum alpha-fetoprotein, tumor size and severity of liver cirrhosis. The results show that increased urinary excretion of free and acetylated polyamines, as well as an altered N1/N8-acetyl-spermidine molar ratio, is a sensible but not specific feature of HCC patients; polyamines may play a role in human carcinogenesis, but their determination does not seem reliable for the early detection of liver cancer.
Preoperative Carbohydrate Antigen 195 (CA195) and CEA Serum Levels as Prognostic Factors in Patients with Colorectal Cancer
Authors: Andicoechea A. , Vizoso F. , Alexandre E. , Cuesta E. , Díez M. Cruz , Riera L. , García-Muñiz J.L. , Martínez E. , Ruibal A.
Published: March 2018

We evaluated in 214 patients with primary colorectal cancer the prognostic value of the preoperative serum levels of CEA and CA195. For CEA these levels were above the cutoff of 6 ng/ml in 31.3% of patients, whereas for CA195 they were higher than 12 U/ml in 35.9% of patients. The simultaneous use of both antigens increased the sensitivity to 49%, which was significantly higher than that of CEA (p<0.001) and CA195 (p<0.01) taken singly. The mean preoperative CEA levels were significantly (p<0.001) correlated with Dukes’ stage only, while there was a significant correlation between preoperative serum levels of CA195 and Dukes’ stage (p<0.001), grade of differentiation (p<0.01) and tumor location (p<0.05).

The results indicated that high preoperative serum levels of CEA and CA195 were associated with a shorter overall survival (p<0.0001). In addition, separate Cox multivariate analysis showed that preoperative CA195 was, after Dukes’ stage, the strongest factor to predict overall survival (p<0.0001).
CA 125: The past and the Future
Authors: Bast R.C. , Xu F.-J. , Yu Y.-H. , Barnhill S. , Zhang Z. , Mills G.B.
Published: March 2018

Over the last 15 years, substantial progress has been made in understanding the potential and the limitations of the CA 125 assay. More than 2000 papers have been published concerning laboratory and clinical studies of CA 125. The original CA 125 assay utilized the OC 125 antibody that recognizes the CA 125 epitope on a high molecular weight glycoprotein. Despite repeated attempts, the gene encoding the peptide component has not yet been cloned. Monoclonal antibodies have been raised against other epitopes expressed by this molecule, leading to the development of the CA 125-II assay that exhibits less day-to-day variation. Using either assay, elevated levels of CA 125 are detected in a number of benign conditions, including endometriosis. CA 125 is most consistently elevated in epithelial ovarian cancer, but can be expressed in a number of gynecologic (endometrial, fallopian tube) and non-gynecologic (pancreatic, breast, colon and lung) cancers. The best established application of the CA 125 assay is in monitoring ovarian cancer. The rate of decline in CA 125 during primary chemotherapy has been an important independent prognostic factor in several multivariate analyses. Persistent elevation of CA 125 at the time of a second look surgical surveillance procedure predicts residual disease with >95% specif city. Rising CA 125 values have preceded clinical detection of recurrent disease by at least 3 months in most, but not all studies. Given the modest activity of salvage chemotherapy, this information has not yet impacted on survival. Rising CA 125 during subsequent chemotherapy has been associated with progressive disease in more than 90% of cases. CA 125 may serve as an effective surrogate marker for clinical response in phase II trials of new drugs. CA 125 levels can aid in distinguishing malignant from benign pelvic masses, permitting effective triage of patients for primary surgery. Early detection of ovarian cancer remains the most promising application of CA 125. An algorithm has been developed that estimates the risk of ovarian cancer (ROC) based upon the level and trend of CA 125 values. A major trial has been initiated that uses the ROC algorithm to trigger transvaginal sonography and/or subsequent laparotomy. Such a trial could demonstrate improvement in survival through early detection. This strategy should provide adequate specificity, but sensitivity for early stage disease may not be optimal. In the future, improved sensitivity may be attained using multiple markers and neural network analysis. Most serum tumor markers have been proteins or carbohydrates, but lipid markers such as lysophosphatidic acid deserve evaluation. Genomic and proteonomic technologies should identify additional novel markers.
CA 125 Production and Release by Ovarian Cancer Cells In Vitro
Authors: Beck E.P. , Moldenhauer A. , Merkle E. , Kiesewetter F. , Jäger W. , Wildt L. , Lang N.
Published: March 2018

The antigenic determinant CA 125 is a high molecular weight glycoprotein which is elevated in more than 80% of patients with epithelial ovarian cancer. Despite its good performance as a human tumor marker, only little is known about its physiological function. According to recent publications, CA 125 production and release appear to be related to cellular growth. In order to investigate this putative relationship more closely, we analyzed the pattern of CA 125 production and release by ovarian cancer cells during exponential cell growth, during cell cycle arrest by colchicine and during inhibition of cellular protein synthesis by cycloheximide. The results were correlated with the cell cycle distribution. According to our results, the main determinant of CA 125 release into the culture supernatant is the total cell count. Although cell cycle arrest in the G2 + M phase by means of colchicine treatment resulted in the death of most cells, which was reflected by an increased release of CA 125, no differences in the intracellular production rate between colchicine treated and untreated cells were seen. In contrast, treatment of cells with cycloheximide not only resulted in decreasing cell numbers but also in a complete inhibition of CA 125 production by surviving cells.
Immunohistochemistry of CA 125
Authors: Nap M.
Published: March 2018

CA 125 is known as the marker that is most strongly associated with epithelial gynecological tumors. Compared to the number of publications on its use in serum assays, the application in immunohistochemistry is still limited. The availability of many good antibodies that perform well in formalin-fixed paraffin-embedded tissue opens good possibilities for a wider use. Outside the gynecological tract several other structures may react positive for CA 125. Among these are the lung and breast but also the epithelial cells of the conjunctiva and to some extent prostate glandular epithelium. In the fetus reactions can be found in the serosal linings of body cavities but also in the esophagus and skin. In diagnostic pathology CA 125 plays a role in identifying the primary locations of metastatic carcinoma of unknown origin. It is recommended to use CA 125 antibodies not in a solitary setting but in combination with CEA, BRST-2 and Vimentin to discriminate best between the most frequent sites of origin of metastatic carcinoma. Regular analysis of sensitivity/specificity ratios in a balanced population, representing the composition of the patient population seen in daily practice, should be performed to evaluate the position of CA 125 in diagnostic immunohistochemistry.
The Role of CA 125 in Screening for Ovarian Cancer
Authors: Rosenthal A.N. , Jacobs I.J.
Published: March 2018

Ovarian cancer has the worst prognosis of any gynaecological malignancy, primarily because it tends to present at an advanced stage. The excellent survival rates of early stage disease have provided the rationale for efforts to detect ovarian cancer early by screening, in the hope that survival rates will be improved. Available data suggests that CA 125 is elevated in the majority of epithelial ovarian malignancies prior to clinical presentation. Large trials of screening for ovarian cancer indicate that using a CA 125 cutoff value of 30 U/mL has good sensitivity, but inadequate specificity for detecting preclinical disease. Use of transvaginal ultrasonography as a second-line test in women with elevated CA 125 levels improves specificity to acceptable levels, as does use of a mathematical algorithm which analyses rates of change of CA 125. Two major randomised controlled trials, investigating the effect of screening strategies incorporating CA 125 on mortality, are currently underway.
Resection Guided by Antibodies (REGAJ) a Reappraisal after 10 Years
Authors: Jäger W. , Ackermann S.
Published: March 2018

Between 1986 and 1990 50 patients with ovarian cancer were submitted to a procedure which we called REGAJ - resection guided by antibodies. Using the radiolabeled murine monoclonal antibody OC 125, microscopic ovarian tumors producing CA 125 were detected during second-look surgery by a hand-held probe. Retrospective analysis after 10 years revealed that this procedure resulted in the cure of 4 of 11 patients, who would otherwise have been considered tumor free during second-look surgery and not further treated. Previous problems associated with the method can now be solved so that the clinical value of the procedure should be reconsidered.
CA 125 in Biological Fluids
Authors: Molina R. , Filella X. , Jo J. , Agusti C. , Ballesta A.M.
Published: March 2018

CA 125 is not a specific tumor marker, and is synthesized by normal and malignant cells of different origin (mainly in tissues derived from the müllerian epithelia) in a similar proportion. Abnormal CA 125 levels may be found in fluids of different origin (ascites, pleura, pericardium, amniotic fluid, cyst fluid, bronchoalveolar fluid, etc.) and in serum from patients with these fluids. Differences in serum CA 125 found in malignant or benign diseases may be related to the number of cells that synthesize the marker, and are highly dependent on the access to serum, where the marker is normally determined. Moreover, CA 125 is a very good tumor marker in ovarian and lung cancer. The sensitivity of CA 125 in ovarian cancer is related to stage (40–95%), histological type (lower levels in mucinous adenocarcinoma), and the marker is useful in the early detection of recurrence (sensitivity 80%) and in therapy monitoring. It's sensitivity in lung cancer is lower than in ovarian cancer, 39% in locoregional malignancies and 69% in metastastatic disease, but clearly related to stage and histology (mainly in adenocarcinomas and large cell lung cancer) and it is useful in prognosis and disease monitoring.
CA 125 in Benign Gynecological Conditions
Authors: Meden H. , Fattahi-Meibodi A.
Published: March 2018

The tumor marker CA 125 was initially thought to be specific for ovarian malignancies. Subsequently it was found to be raised in a variety of benign conditions, including pregnancy, pelvic inflammatory disease, tuberculosis and cirrhosis of the liver. With respect to gynecological tumors, CA 125 may be elevated in benign ovarian cysts, tubo-ovarian abscess, endometriosis, hyperstimulation syndrome, ectopic pregnancy and fibroids. These results demonstrate that CA 125 is a marker of non-specific peritoneal conditions.
C-erbB-2 Expression in Primary Breast Cancer
Authors: Tagliabue E. , Ménard S. , Robertson J.F.R. , Harris L.
Published: March 2018

c-erbB-2 is an oncoprotein which is overexpressed in up to 40% of primary breast cancers. c-erbB-2 overexpression is a bad prognostic factor in patients with lymph node-positive disease. Unfortunately, there has been no agreement to date on whether c-erbB-2 overexpression is of prognostic significance in patients with lymph node-negative disease. c-erbB-2 overexpression is correlated with the absence of estrogen receptor expression in a number of publications. Correlation between c-erbB-2 overexpression and hormone sensitivity in the clinical setting is less well established and is the focus of ongoing studies. Both preclinical and clinical studies support an association between c-erbB-2 receptor overexpression and resistance to alkylating agents. In contrast, the data for c-erbB-2 and anthracyclines should be viewed in a slightly different manner. Anthracyclines appear to have a greater therapeutic effect in c-erbB-2-positive disease which may be dose sensitive. In c-erbB-2-negative disease not only is the therapeutic effect reduced but there does not appear to be any improved response to higher doses of anthracyclines. The data for c-erbB-2 and the taxanes is still not clear enough to provide any definite conclusions. If there is a correlation it would at present appear to be between paclitaxel and response rates, but this needs to be confirmed in larger studies. Few studies have looked at changes in c-erbB-2 on therapy. Those that have seem to show no significant change on either tamoxifen or chemotherapy.
TPA and CA 15.3 Measurements for Breast Cancer Monitoring in a Routine Setting
Authors: Bonfrer J. M.G. , Korse C. M.
Published: March 2018

TPA and CA 15.3 concentrations were routinely determined in serum of patients treated for breast cancer during a 15-month period. ROC curves did not show differences in the ability to differentiate between NED and PD on the basis of matching tumor marker values. During monitoring of patients with NED, TPA levels showed fluctuations of more than 25% that were not disease related. We concluded that CA 15.3 is a more slowly reacting marker of tumor burden than TPA, which is an immediate indicator of cell turnover.
TPS Monitoring in Metastatic Breast Cancer
Authors: Van Dalen A.
Published: March 2018

The management of metastatic breast cancer patients reflects the heterogeneous nature of the disease. While patients may benefit from hormonal treatment, in most cases more toxic chemotherapy is applied in the advanced stages. The pretreatment levels of TPS in patients with metastatic breast cancer are correlated with prognosis. Decreasing TPS levels (>50%) during treatment are indicative of response. The fastest decrease in TPS levels is obtained in patients with a favorable prognosis. Increasing TPS levels (>25%) predict disease progression with a considerable lead time (median 8 months). The clinical impact of these observations is discussed in this paper.
Correlation of Biochemical Tumor Markers with Conventional Pathological Features in Primary Breast Cancer
Authors: Péley G , Bezzegh A. , Besznyák I. , Doleschall Z. , Csuka O. , Péter I. , Tóth J. , Számel I. , Schumann B. , Ottó S.
Published: March 2018

In this prospective study the correlation of pathological with biological prognostic factors and serum tumor markers has been investigated in 574 patients with primary invasive breast cancer. The p53 protein and Bax level correlated positively with tumor size, lymph node status and histological grade. The serum levels of CEA, CA 15.3, TPA-M and TK correlated with tumor extent. There was a significant difference between pre- and postmenopausal breast cancer patients in serum levels of TPA-M and cytosol levels of Bax. Whether these correlations can help in predicting the prognosis of breast cancer by providing additional information with respect to the conventional factors, will have to be investigated by several years of careful clinical follow-up.
C-erbB-2 in Serum of Patients Receiving Fractionated Paclitaxel Chemotherapy
Authors: Lüftner D. , Schnabel S. , Possinger K.
Published: March 2018

Humanized anti-c-erbB-2 antibodies (Herceptin®) in a weekly schedule are a new therapeutic option for the treatment of c-erbB-2-positive, advanced breast cancer (ABC). Addition of Herceptin® to first-line chemotherapy for c-erbB-2 overexpressing ABC increased anticancer activity in a randomized phase III trial. However, except from standard UICC response criteria, there are hitherto no recommendations as to how to monitor Herceptin® therapy. In a therapy optimizing study with weekly dose-intensified paclitaxel monotherapy (schedule: 90 mg/m2 weekly x 6, q9w), we correlated the clinical course of stage IV breast cancer in UICC criteria with the course of the shed c-erbB-2 protein fragment and the CA 27.29 serum level. Serum samples were taken weekly from 35 patients to measure the serum c-erbB-2 and CA 27.29 protein levels over time. Up to now, 10 patients (28.5%) are c-erbB-2 positive (>15 U/mL), with a median baseline protein expression of 65 U/mL. While the overall response rate in the study is 36%, the response rate among c-erbB-2-positive patients is 62%, indicating a high sensitivity of c-erbB-2 positive patients to dose-intense paclitaxel treatment. In all responders the c-erbB-2 serum level decreased below the detection limit either before the clinical diagnosis of response or by the end of the next cycle. However, the normalization of the c-erbB-2 serum level was not specific for responders as patients with stable or progressive disease presented normalized levels or a >50% decrease of the baseline level, too. The courses of the c-erbB-2 protein levels correlated closely with the courses of CA 27.29. The decrease in the serum c-erbB-2 oncoprotein level might indicate a regression of c-erbB-2 positive tumor load. This may even happen in progressive disease according to UICC criteria when the c-erbB-2-negative tumor fraction progresses while the c-erbB-2-positive fraction is controlled. Another explanation would be that the mechanisms of c-erbB-2 shedding change under chemotherapy, with less of the c-erbB-2 protein fragment being released to the serum, which would make the c-erbB-2 positive tumor cells a better target for anti-c-erbB-2 antibody treatment.
Relationship between Steroid Receptors (As Continuous Variables) and Response to Adjuvant Treatments in Postmenopausal Women with Node-Positive Breast Cancer
Authors: Coradini D. , Oriana S. , Biganzoli E. , Marubini E. , Boracchi P. , Bresciani G. , Di Fronzo G. , Daidone M.G.
Published: March 2018

In current clinical practice for breast cancer patients, estrogen (ER) and progesterone receptor (PgR) concentrations, quantified by the dextran-coated charcoal assay, are categorized by an arbitrary cutoff into a negative or positive status. However, although the results obtained with this approach are easy to interpret, such a representation could oversimplify the relationship between ER and PgR content and patient outcome and imply an assumption of monotonicity, which is generally expected but rarely proven. We evaluated the relationship between ER and PgR content (considered on a continuous scale) and clinical outcome, using a flexible statistical model, in a group of postmenopausal patients with N-positive operable tumors who were submitted to surgery and different adjuvant treatments (tamoxifen or CMF). Univariate analysis indicated that in the tamoxifen-treated group, ER level, number of metastatic nodes (pN) and age, but not PgR, were significant indicators of clinical outcome (p=0.032, p=0.021 and p=0.029, respectively). Multivariate analysis indicated that in this group of patients there was no interaction between variables, and in the final model for disease-free survival (DFS) only ER and pN were retained with an overall predictive ability of the regression model of 0.723, as evaluated by Harrell's c. However, pN markedly contributed to the predictive ability of the model with respect to ER, since a marked decrease in Harrell's c statistic (c=0.582) was observed when pN was removed from the model. In the CMF-treated group, only pN affected clinical outcome. When the estimated DFS curves obtained from the final Cox regression models were plotted according to four values of ER (in the tamoxifen-treated group) or three values of pN (in the CMF-treated group) we observed that in the tamoxifen-treated group patients with an ER concentration equal to 0 fmol/mg cytosol protein had the worst prognosis, whereas a marked improvement of the expected DFS was observed for patients with a low but detectable ER level (generally classified as ER-negative because falling below the conventional cutoff value of 10 fmol/mg cytosol protein). Our results seem to suggest that the use of steroid receptor concentrations on a continuous scale, instead of dichotomous “status”, is to be preferred in the choice of adequate therapeutic strategies.
Production of a Monoclonal Antibody Directed against the High-Affinity Nerve Growth Factor Receptor
Authors: Tagliabue E. , Ghirelli C. , Lombardi L. , Castiglioni F. , Asnaghi L. , Longhi C. , Borrello M.G , Aiello P. , Ménard S.
Published: March 2018

The high-affinity nerve growth factor receptor corresponds to the tyrosine protein kinase encoded by the proto-oncogene trkA. Different findings suggest that nerve growth factor (NGF) can be operative in the growth modulation of tumor cell lines possessing high-affinity binding sites for this molecule. Using as immunizing material the SKNBE neuroblastoma cell line transfected with proto-trkA we produced a monoclonal antibody (MAb) able to recognize the high-affinity nerve growth factor receptor. The selected MAb, designated MGR12, is directed against an epitope present on the extracellular domain of the receptor since it showed reactivity on living trkA-expressing cells and was able to immunoprecipitate the proto-trkA molecule. The MGR12 MAb is directed against a non-functional epitope since it neither inhibited NGF binding nor induced receptor internalization. This new reagent appears to be an appropriate tool for analyzing the expression of high-affinity nerve growth factor receptor in tumors of different origin and for elucidating its involvement in tumor progression.
Utility of Tumor Marker CA 72.4 in Patients with Chronic Renal Failure
Authors: Vitores A. Ma. González , Duró G. Encabo , Fraile B. Bermejo , Miró A. Olmos , Carrasco M. Armengol
Published: March 2018

The tumor marker CA 72.4 is composed of two monoclonal antibodies, B 72.3 and cc49, which detect the glycoprotein TAG 72 present in tumor cells. The levels of CA 72.4 may be modified depending on the route of excretion of the antigen TAG 72. The objective of this study was to evaluate the behavior of CA 72.4 in healthy subjects and to assess the influence of chronic renal failure (CRF) on the levels of this tumor marker.

Random serum samples were collected in 181 individuals (148 healthy volunteers and 33 patients with CRF) and 214 determinations of CA 72.4 were performed. We also performed 66 determinations of plasma creatinine. In healthy subjects the cutoff value of CA 72.4 was established at 3 U/mL, with a sensitivity of 53% and a specificity of 85.8%. In the CRF patients we found no statistically significant differences when we compared the values of CA 72.4 predialysis and postdialysis (p=0.197). However, a statistically significant difference was found in the plasma creatinine levels (p<0.001).

Chronic renal failure does not affect the result of CA 72.4 determinations; this tumor marker may therefore be useful in the monitoring of patients with cancer, independent of their renal function.
The biological Markers of Non-Hodgkin'S Lymphomas: Their Role in Diagnosis, Prognostic Assessment and Therapeutic Strategy
Authors: Morra E.
Published: March 2018

The biological markers of non-Hodgkin's lymphomas (NHL) are distinguished in three categories: serological, immunophenotypic, and molecular markers. The clinical importance of biological markers in NHL is based on their support of morphologic diagnosis, their role in staging and prognostic assessment, and their contribution to monitoring minimal residual disease (MRD). The most important serological markers reflect the tumor load (beta-2 microglobulin, β2-M), proliferative activity (lactic dehydrogenase, LDH), and invasive potential of lymphomas (CA 125). LDH and β2-Mare included as important prognostic parameters in widely used staging systems. Immunophenotypic analysis identifies specific markers of lineage (B or T-cells), maturation level, cell proliferation, and clonality. Results of immunophenotyping are particularly useful in low to intermediate-grade NHLs to support the morphologic diagnosis and facilitate the detection of MRD after treatment. The molecular markers are genetic lesions involved in the pathogenesis of some categories of NHL. Their use as markers for diagnosis is justified by the selective association with specific lymphoma categories: follicular, mantle cell, diffuse large cell, and anaplastic large cell lymphomas. Molecular lesions are the most specific and sensitive markers for evaluating MRD. Today the biological markers of NHL are widely employed for diagnosis, staging, and prognostic assessment. Their systematic use may complement clinical parameters in the stratification of NHL patients, who may thus become candidates for treatments of different intensity. The detection of MRD after first-line treatment identifies patients at high risk of relapse who require additional therapy to cure their disease.
Urinary 5α-Androstanediol and 5β-Androstanediol Measurement by Gas Chromatography after Solid-Phase Extraction and High-Performance Liquid Chromatography
Authors: Minut G.J. , CambiÈ M. , Lanzoni M. , Marubini E. , Secreto G.
Published: March 2018

Urinary androstanediol measurement, often in association with other androgens, is commonly used to support the clinical diagnosis of idiopathic hirsutism. In addition, androgen excess has been shown to be the endocrine abnormality which characterizes patients with breast cancer. We recently developed a method for the measurement of urinary testosterone employing solid-phase extraction and HPLC purification before quantitative measurement by gas chromatography. In the present report we verify the feasibility of the method for the simultaneous measurement of 5α-androstane-3α,17β-diol and 5β-androstane-3α,17β-diol in addition to testosterone in the same urine sample. The mean recovery for the whole procedure was 89.8% for 5α-androstane-3α,17β-diol and 87.8% for 5β-androstane-3α, 17β-diol. The estimates of the coefficients of variation were 4.9% (95% confidence limits: 3.9–6.5%) and 3.9% (95% confidence limits: 3.1–5.2%), respectively. Accuracy was evaluated by standard addition and dilution assays and a linear relationship was found between expected and observed values (r2=0.997 for 5α-androstane-3α,17β-diol and r2=0.999 for 5β-androstane-3α,17β-diol). The method is rapid, effective and suitable for the measurement of testosterone, 5α-androstanediol and 5β-an-drostanediol in the same urine sample.
Chromogranin-A as a Serum Marker for Neuroendocrine Tumors: Comparison with Neuron-Specific Enolase and Correlation with Immunohistochemical Findings
Authors: Giovanella L. , la Rosa S. , Ceriani L. , Uccella S. , Erba P. , Garancini S.
Published: March 2018

Background

Chromogranin-A (Cg-A) is a 439-amino-acid protein contained in secretory granules of neuroendocrine cells, in addition to specific hormone peptides or neuropeptides. Since Cg-A is co-released with peptide hormones its serum concentration can be used as a marker of neuroendocrine tumors.

Aim

Evaluation of the analytical performance of a new IRMA method for Cg-A assay and of the clinical value of serum Cg-A and neuron-specific enolase (NSE) in neuroendocrine tumors. In addition, we compared the diagnostic usefulness of both Cg-A and NSE serum levels and their relationship to tissue expression.

Patients and methods

Initially we evaluated the analytical performance (intra- and interassay imprecision, dilution test and detection limit) of the Cg-A RIACT method (CIS Bio-International, Gifsur-Yvette, France). We selected 50 patients affected by various histologically confirmed neuroendocrine tumors (NETs): 111In-pentetreotide scan and helical computed tomography were employed to assess tumor extent. Cg-A and NSE were measured before surgery in serum samples of patients and 50 age-matched controls by IRMA methods. After surgery immunohistochemical stains for Cg-A and NSE were performed on surgical specimens of tumor tissue.

Results

Cg-A levels were significantly higher (p<0.0001) in patients with NETs than in healthy controls and we found a positive correlation between serum and tissue expression (p<0.05). Serum levels of Cg-A were also related to tumor extent (p<0.05) but in some cases we observed significant elevation of serum Cg-A in small, intensely immunoreactive NETs. ROC curve analysis showed better accuracy for serum Cg-A compared to NSE in the diagnosis of NETs, while no significant relationship was found between serum expression and immunostaining for NSE.

Discussion

Our results confirmed the biological and clinical significance of circulating Cg-A as an expression of granular content in neuroendocrine tissues and supported the complementary usefulness of serum Cg-A in the diagnosis and evaluation of NETs together with imaging modalities.
Angiogenesis at the Interface between Basic and Clinical Research
Authors: Albini A. , Noonan D. , Santi L.
Published: March 2018

The field of antiangiogenesis has shown a remarkably rapid evolution from the discovery at the bench to translation into the clinic. Currently a wide variety of compounds are in clinical trial as inhibitors of angiogenesis, and new compounds are being frequently added. The target cell of most angiogenesis inhibitors is the endothelial cell, with inhibitors that selectively affect a number of endothelial cell functions acquired during angiogenesis, including activation, proliferation, migration, invasion and survival. The endothelial cell may also be targeted by chemotherapeutic agents currently in use. The high doses and intermittent treatment schedules used to fight resistant tumor cells may be altered towards lower doses and chronic administration to obtain selective inhibition of angiogenic factor-stimulated endothelial cells as adjuvant therapy. Finally, gene therapy is a promising route for the delivery of novel protein inhibitors of angiogenesis, and is actively being investigated.
Models for Studying Angiogenesis in Vivo
Authors: Ribatti D. , Vacca A.
Published: March 2018

In vivo and in vitro techniques are available for reseach on the functions of endothelial cells during angiogenesis. In this review we describe and evaluate the methodology and specific features of some of the most frequently used in vivo assays.