bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Value of the Glycoprotein TAG-72 in Patients with Gastric Cancer
Authors: Vitores A.M. González , Duró G. Encabo , Fraile B. Bermejo , Carrasco M. Armengol
Published: March 2018

The specificity of the tumor markers used to date in patients with gastric cancer has not been satisfactory. For this reason we decided to evaluate the utility of TAG-72 in this disease. Between 1993 and 1998 we determined the levels of TAG-72 in 638 subjects (148 healthy volunteers, 33 patients with chronic renal failure (CRF), 149 patients with benign diseases of the liver, 95 patients with benign gastrointestinal diseases and 213 patients with gastric cancer). TAG-72 was measured using an IRMA method. Statistical analysis of the data was performed with the BMDP package. We established a cutoff for TAG-72 of 3 U/mL, corresponding to the 92.6th percentile of the healthy controls. We observed that neither CRF nor benign liver diseases affected TAG-72 levels, while certain benign gastrointestinal diseases did cause alterations of the marker. Using Cox multivariate analysis we discovered that the preoperative TAG-72 level was an independent prognostic variable associated with both disease-free and overall survival. We conclude that, although TAG-72 is not useful for the diagnosis of gastric cancer, it is a suitable tool for disease monitoring and prognostic assessment.
Soluble Urokinase Plasminogen Activator Receptor Measurements: Influence of Sample Handling
Authors: Riisbro R. , Christensen I.J. , Høgdall C. , Brünner N. , Høgdall E.
Published: March 2018

Aim

The influence of sample handling on soluble urokinase plasminogen activator receptor (suPAR) concentrations in serum and EDTA plasma was studied in 16 healthy premenopausal women.

Method

Blood was collected in dry tubes and tubes containing EDTA and kept at 4°C or 20°C for 1, 3, 8, 24 or 72 hours before processing into serum or EDTA plasma. In addition, serum and EDTA plasma were frozen and thawed 1–8 times. All suPAR measurements were performed by ELISA.

Results

No significant differences were found between serum or EDTA plasma suPAR concentrations when whole blood samples were kept for 1, 3, 8 or 24 hours. Significantly higher suPAR levels were found in samples kept for 72 hours at 20°C compared to samples processed into serum or EDTA plasma after short-term storage for no more than 24 hours after collection. No significant differences were observed when whole blood was kept at 4°C for up to 72 hours. Repeated freezing and thawing had no significant effect on the serum and EDTA plasma suPAR levels.

Conclusion

suPAR values in blood samples are dependent on the handling procedures of the samples. All samples of whole blood must be processed into EDTA plasma or serum within 24 hours if kept at 20°C and within 72 hours if kept at 4°C. However, repeated freezing/thawing cycles had no influence on suPAR values in the samples.
Immunohistochemical Study of Pepsinogen C Expression in Cutaneous Malignant Melanoma: Association with Clinicopathological Parameters
Authors: Quintela I. , Vizoso1 F. , Serra C. , González1 L.O. , Fernández1 R. , Merino A.M. , Baltasar A.
Published: March 2018

Background

The aim of this study was to evaluate the pepsinogen C expression in malignant cutaneous melanomas and analyze its possible relationship to clinical and pathological parameters. Pepsinogen C is an aspartyl proteinase primarily involved in the digestion of proteins in the stomach and represents one of the main androgen-inducible proteins in breast cancer cells.

Method

Tumoral pepsinogen C expression was retrospectively analyzed in 35 paraffin-embedded tissues from patients with primary malignant cutaneous melanoma and in 10 samples from 10 benign lesions (4 dermal melanocytic nevi, 4 compound melanocytic nevi and 2 dysplastic melanocytic nevi), using immunohistochemical methods.

Results

The benign lesions were consistently negative for pepsinogen C, whereas 20 of the 35 malignant melanomas (57%) showed positive immunostaining for pepsinogen C. The percentage of pepsinogen C-positive tumors was significantly higher in men than in women (p=0.01) and in epithelioid melanomas than in fusocellular or mixed type melanomas (p=0.003). In addition, the percentage of pepsinogen-C positive tumors was positively and significantly correlated with lesion thickness (p=0.003), Clark's level of invasion (p=0.028) and tumor stage (p<0.001).

Conclusion

Pepsinogen C could be a new prognosticator of unfavorable outcome in cutaneous malignant melanoma.
Differential Expression Levels of Urokinase-Type Plasminogen Activator and Cathepsin D in Locally Advanced Laryngeal Squamous Cell Carcinoma: Clinical Implications
Authors: Leto G. , Tumminello F.M. , Gebbia N. , Bazan V. , Tomasino R.M. , Dardanoni G. , Russo A.
Published: March 2018

The expression levels and the prognostic impact of urokinase-type plasminogen activator (uPA) and cathepsin D (CD) were evaluated in patients with locally advanced laryngeal squamous cell carcinoma (LSCC). uPA and CD protein levels were determined by immunoluminometric or immunoenzymatic assays in the cytosol of paired sets of tumor tissues and corresponding adjacent normal mucosa (NLM) from 57 patients with stage III/IV LSCC and were correlated with a number of clinicobiological parameters of this tumor including anatomical site, tumor grade, nodal status, clinical stage, DNA ploidy, proliferation rate, and patient outcome. Median uPA levels were significantly higher in LSCC than in NLM (1.8 ng/mg of protein vs 0.3 ng/mg; p<0.001) whereas median CD levels were not significantly increased in tumor tissue compared to NLM (24 pmol/mg vs 19 pmol/mg, p=0.063). No significant correlation was observed between uPA and CD concentrations in tumor tissues (r=-0.1; p=0.4). Furthermore, the distribution analysis of uPA and CD in tumors showed no correlation between expression levels of these proteinases and the parameters mentioned above including patient outcome. However, when data were matched according to each parameter examined it was observed that the differences in uPA content between LSCC and NLM, expressed as uPA tumor/normal tissue ratio (T/M), were more marked in clinically advanced and/or aggressive forms of LSCC (i.e., node positive, stage IV, poorly and moderately differentated, aneuploid multiclonal, low S-phase, subglottis tumors). These data suggest that in such tumors altered regulation of uPA may occur to a greater extent than in less aggressive and less advanced forms of LSCC. This phenomenon was not observed for CD. However, in tumors with a high proliferation rate, in stage IV tumors as well as in those located in the supraglottis, CD levels were significantly higher than those found in the corresponding NLM (p=0.008, p=0.02 and p=0.03, respectively). In conclusion, uPA is highly expressed in locally advanced LSCC and appears to be implicated in some key events of progression of this tumor such as local invasion and/or nodal involvement, whereas CD does not seem to have a role in promoting these processes. Nevetheless, neither of these proteinases seem to be prognostically useful in patients with stage III/IV tumors.
Evaluation of Chromogranin a Expression in Serum and Tissues of Breast Cancer Patients
Authors: Giovanella L. , Marelli M. , Ceriani L. , Giardina G. , Garancini S. , Colombo L.
Published: March 2018

Human chromogranin A (CgA) is a member of the granin family and is widely distributed in large dense core granules of endocrine and neuroendocrine cells. A variety of non-neuroendocrine carcinomas arising in various tissues show patterns of neuroendocrine differentiation. Expression of CgA has been documented in epithelial cells of normal mammary gland as well as in breast cancers, and elevation of serum CgA has been detected in patients with breast cancer. Our study was undertaken to evaluate the relationship between serum CgA levels and neuroendocrine features in breast cancer. In addition, we evaluated the expression of serum CgA in patients affected by breast cancer compared to controls and the relationship between serum CgA and tumor histology, extent of disease, lymph node status, tumor stage and serum CA 15.3 levels. We enrolled 266 patients with infiltrating ductal or lobular breast carcinoma and a group of 100 age-matched healthy women serving as controls. Serum CgA and CA 15.3 were assayed by specific immunoradiometric methods. The overall sensitivity of CgA and CA 15.3 was 0.06 and 0.34, respectively (χ219.1, p<0.0005). No relationship was found between serum levels of CgA and tumor histology, extent of disease, lymph node status or tumor stage while serum levels of CA 15.3 were strongly correlated with all these variables but tumor histology. No relationship was found between serum levels of CgA and CA 15.3. Immunostaining against CgA, CgB, NSE and synaptophysin was performed on primary tumor tissue of 14 serum CgA-positive and 24 serum CgA-negative patients and was negative in all cases. We also evaluated eight cases of pathologically-proven neuroendocrine breast cancer: only four and two of these showed positive CgA immunostaining and increased serum CgA concentration, respectively. In conclusion, serum CgA assay offers no additional information regarding the presence, the extent and the histology of breast cancer compared to the CA 15.3 assay. Moreover, serum CgA was not an accurate marker to identify or exclude the rare neuroendocrine differentiation of breast cancer. We therefore conclude that CgA is not useful as a serum marker in breast cancer.
Diagnostic and Prognostic Significance of Inflammatory Markers in Lung Cancer-Associated Pleural Effusions
Authors: Kotyza Jaromír , Havel David , Vrzalová Jindra , Kulda Vlastimil , Pešek Miloš
Published: March 2018

Besides massive expression in inflammatory pleural effusions, inflammatory markers are also present in cancer-induced pleural effusions. Recent advances in cancer biology point to a role of inflammatory signaling in cancer and encourage reconsidering the diagnostic and prognostic value of inflammatory markers. Here an attempt was made to relate protein levels of inflammatory markers to underlying malignant processes in the pleural space.

Pleural effusions from lung cancer patients (n=116) were subjected to a multifactorial analysis covering 13 inflammatory markers. The composition of tumor-associated effusions was compared with that of parainflammatory pleural effusions (n=30), transudates (n=18), and serum values, and evaluated in relation to cancer origin, histology, cytology, pleural involvement, treatment history, and survival time.

Inflammatory markers were significantly expressed in pleural effusions of paraneoplastic origin when compared to transudates and most serum levels. Values in pleura-invading and metastatic tumor-associated effusions were typically higher than those of other tumors. Many markers correlated negatively with survival, most prominently IL-8 (r=–0.36, p=0.001) and VEGF (r=–0.35, p=0.001).

It appears that most inflammatory markers are highly expressed in tumor-associated pleural effusions, reflecting to some extent tumor origin and localization. Despite the lower efficacy of inflammatory markers in the differentiation between exudative pleural effusions, some inflammatory markers may represent potential prognostic markers of malignant processes in the pleural space.
HIF-1α is a Prognostic Marker in Oral Squamous Cell Carcinomas
Authors: Eckert Alexander W. , Schütze Andreas , Lautner Matthias H.W. , Taubert Helge , Schubert Johannes , Bilkenroth Udo
Published: March 2018

The critical molecular regulator of hypoxia is the hypoxia-inducible factor 1 alpha (HIF-1α). The prognostic impact of this regulator protein in oral squamous cell carcinomas (OSCC) has not been comprehensively investigated. The aim of this study was to analyze the expression of HIF-1α in 82 patients with OSCC and to correlate it with their disease-specific survival. Immunohistochemical staining for HIF-1α was performed on 82 OSCC specimens using a standard immunoperoxidase technique. The expression of HIF-1α was correlated with poor disease-specific survival for OSCC patients. Patients with negatively or weakly HIF-1α–expressing tumors had a survival rate of 80%, whereas the survival decreased to only 33.6% in case of moderate or strong expression. In multivariate Cox regression analysis, we found a 3.5-fold increased risk of tumor-related death when HIF-1α was strongly expressed (p=0.016) compared to negative or weak expression of HIF-1α. We suggest HIF-1α is an independent prognostic marker in OSCC. Immunohistochemical detection of HIF-1α appears to be useful in the diagnosis of OSCC and to provide prognostic information in addition to TNM stage and histological grade.
Cervical Cytology Biobanking in Europe
Authors: Arbyn Marc , Van Veen Evert-Ben , Andersson Kristin , Bogers Johannes , Boulet Gaëlle , Bergeron Christine , von Knebel-Doeberitz Magnus , Dillner Joakim
Published: March 2018

A cervical cytology biobank (CCB) is an extension of current cytopathology laboratory practice consisting in the systematic storage of Pap smears or liquid-based cytology samples from women participating in cervical cancer screening with the explicit purpose to facilitate future scientific research and quality audit of preventive services. A CCB should use an internationally agreed uniform cytology terminology, be integrated in a national or regional screening registry, and be linked to other registries (histology, cancer, vaccination). Legal and ethical principles concerning personal integrity and data safety must be respected strictly. Biobank-based studies require approval of ethical review boards.

A CCB is an almost inexhaustible resource for fundamental and applied biological research. In particular, it can contribute to answering questions on the natural history of HPV infection and HPV-induced lesions and cancers, screening effectiveness, exploration of new biomarkers, and surveillance of the short- and long-term effects of the introduction of HPV vaccination. To understand the limitations of CCB, more studies are needed on the quality of samples in relation to sample type, storage procedures, and duration of storage.
Igf-Ii Mrna Expression in Breast Cancer: Predictive Value and Relationship to Other Prognostic Factors
Authors: Fiore Emilio , Campani Daniela , Muller Ilaria , Belardi Valentina , Giustarini Elisa , Rossi Giovanni , Pinchera Aldo , Giani Claudio
Published: March 2018

Purpose

Insulin-like growth factor-II (IGF-II) is an important regulator of tumor growth in breast cancer. In this study we have examined the prognostic value of IGF-II mRNA expression in breast cancer and its relationship to other predictive parameters.

Patients

Sixty-eight women with infiltrating ductal carcinoma were given the same treatments including mastectomy and antitumoral therapies and followed up for 5 years.

Results

The overall 5-year survival rate was 73.5% (55/68). IGF-II mRNA was expressed in 33/64 patients (51.6%) and had no significant impact on survival. The expression of estrogen receptor (ER) and progesterone receptor (PgR) did not significantly affect the 5-year survival, but in the presence of an IGF-II mRNA signal, the survival of ER- and PgR-negative patients (n=9) was lower than that of ER- and PgR-positive patients (n=15), although the difference was not significant. The 5-year survival was not significantly different between Ki-67-positive and negative patients, but in the IGF-II positive group Ki-67-positive patients (n=7) had a significantly poorer prognosis than Ki-67-negative patients (n=26). The expression of p53 protein was associated with a poorer prognosis: 6/11 (54.5%) p53-positive patients died in the first 26 months of follow-up and 5 of these 6 patients (83.3%) also had positive IGF-II mRNA expression.

Conclusions

IGF-II mRNA expression per se is not an independent predictive factor in breast cancer but may be a marker of poor prognosis when associated with other prognostic factors such as Ki-67 index and p53 expression.
Clinical Value of a Mucin-Like Carcinoma-Associated Antigen (MCA) in Patients with Carcinomas of the Kidney and the Urinary Collecting System
Authors: Miserez A.R. , Müller-Brand J. , Rist M. , Múcke H.
Published: March 2018

A new tumor marker, mucin-like carcinoma-associated antigen (MCA), was evaluated in thirty-four patients with renal cell carcinomas andforty patients with carinomas of the urinary collecting system. In the first group, specificity was 95%, sensitivity 65%, the predictive value for positive diagnosis was 94%, andfor negative diagnosis 72%. In the second group specificity was 83%, sensitivity 71%, predictive value for positive diagnosis was 63%, and for negative diagnosis 88%. Receiver operating characteristic curves indicated that the maximum amount of information was greater in patients of the first group than the second (0.379 vs. 0.332 bits). In the light of these data, the MCA test can be recommended for assessing metastatic spread in patients particularly with renal cell carcinomas.
Impact of Preoperative CA 15-3 Levels in Operable Breast Cancer. Comparison with Tissue Polypeptide Antigen (TPA) and Carcinoembryonic Antigen (CEA)
Authors: Iaffaioli R.V. , Caponigro F. , Esposito G. , Pagliarulo C. , Deplacido S. , Ungaro B. , Bazzicalupo L. , Frasci G. , Bianco A.R.
Published: March 2018

CA 15-3, TPA and CEA were assayed before surgery in 60 patients with breast cancer. A significant association was found between preoperative CA 15-3 levels and some of the most important prognostic factors in breast cancer, such as lymph node status and tumor size. No similar association was discovered for CEA and TPA.

Preoperative CA 15-3 levels were also significantly associated with early recurrences of the disease, thus adding useful information to prognosis especially in N + patients.
The Clinical Status of Immunoscintigraphy with Monoclonal Antibodies in Ocular Melanoma
Authors: Schaling D.F. , Jager M.J. , Van Kroonenburg M.J.P.G. , Oosterhuis J.A. , Pauwels E.K.J.
Published: March 2018

A summary is given of data on the clinical experience with the antimelanoma antibody 225.28S in ophthalmology and the tissue expression of the high molecular weight-melanoma associated antigen in choroidal melanoma. Results are discussed in relation to other detection methodsfor ocular melanoma currently employed by the ophthalmologist.
Complementation of Expression of Carcinoembryonic Antigen and Tumor Associated Glycoprotein-72 (TAG-72) in Human Colon Adenocarcinomas
Authors: Simpson J.F. , Primus F. James , Schlom J.
Published: March 2018

Enzyme-labeled monoclonal antibodies (MAbs) were used in an immunohistochemical, dual-staining study of 10 colon adenocarcinomas. MAbs B72.3 and COL-4, reactive with the high molecular weight tumor-associated glycoprotein-72 (TAG-72) antigen and carcinoembryonic antigen (CEA), respectively, were labeled with horseradish peroxidase or alkaline phosphatase. Dual staining using the two MAbs on a single tissue section (formalin-fixed, paraffin-embedded) showed that greater numbers of carcinoma cells could be detected by using the combination of the two MAbs than could be detected by use of either MAb alone. In many tumors, some carcinoma cells reacted with MAb B72.3, some reacted with MAb COL-4, and some cells reacted with both MAbs. Only 1 of 10 carcinomas showed > 75% reactive cells when stained with each MAb individually. In 9 of 10 cases, however, > 75% of cells reacted when the combination of MAbs was used. Cell surface and cytoplasmic patterns of reactivity were observed with both MAbs while some pools of extracellular mucin were composed of both TAG- 72 and CEA. This study supports the rationalefor the use of a combination of anti-TAG-72 and anti-CEA MAbs for in vitro immunologic detection and potential in vivo immunodiagnostic and immunotherapeutic applications for these MAbs in colon adenocarcinoma patients.
A New Procedure for Gangliosidic N-Acetylneuraminic Acid Analysis in Serum
Authors: Gornati R. , Rapelli S. , Montorfano G. , Cattaneo C. , Berra B.
Published: March 2018

In this paper a method is presented which is suitable for the extraction, purification and analysis of serum gangliosides. The advantage in comparison with other previously published procedures is the complete extraction of sialoglycolipids without contamination of sialoglycoproteins and/or sialoglycopeptides. The method could be used as a second-level test for the diagnosis and follow-up of cancer patients, and also could be potentially used for pharmaco-kinetic studies after ganglioside treatment.
Blood Levels of IGF-I in Non-Small Cell Lung Cancer: Relation to Clinical Data
Authors: Tisi E. , Lissoni P. , Rovelli F. , Mandelli D. , Barni S. , Tancini G.
Published: March 2018

Recent observations have demonstrated that somatomedins, mainly insulin-like growth factor-I (IGF-I), are growth factors for non-small cell lung cancer (NSCLC). On the basis of this evidence, a study was started to evaluate serum levels of IGF-I in a group of untreated NSCLC patients. The study included 46 patients, 25 of whom had an operable tumor, while the other 21 showed distant organ metastases. IGF-I and GH serum levels were measured by RIA in each patient; moreover, in operable patients, hormonal detections were made either before, or 7 days after surgery. The control group comprised 38 age-matched healthy subjects. Mean serum levels of IGF-I were significantly higher in cancer patients with respect to controls, while no difference was seen in mean GH values. Moreover, patients with metastases showed significantly higher levels of IGF-I than the patients without. Within the operable group, patients with lung adenocarcinoma had higher levels of IGF-I than those with epidermoid cell carcinoma, but this difference was not significant. Finally, no significant difference in IGF-I mean values was seen before and after surgical removal of tumors. This preliminary study shows that NSCLC patients may present abnormally high levels of IGF-I. Because of the stimulating role of IGF-I on NSCLC growth, this evidence could play a role in the clinical course of neoplastic lung disease.
A Role for Tumor Markers in Therapeutic Decisions after Chemotherapy Induction of Objective Remission in Stage III Epithelial Ovarian Neoplasms
Authors: Pirtoli L. , Risso G. , Inaudi P. , Landoni F. , Pepi F. , Bindi M. , Tucci E. , D'antona N. , Mangioni C.
Published: March 2018

The management of advanced stage ovarian carcinomas is presently based on initial surgical debulking, multiple drug chemotherapy including cisplatinum, second-look laparotomy. Such an aggressive approach has improved objective response rates and expected survival time, but no dramatic change has been demonstrated as for definitive cure percentages. Many Authors have attempted to turn an optimal objective response to chemotherapy (no residual or minimal residual disease at second-look) into a definitive cure with irradiation. Some reports show satisfactory results, but a high incidence of bowel obstructive complications has been demonstrated, probably due to multiple surgical manipulations before radiotherapy. A reliable diagnostic tool, that could help to avoid the second-look laparotomy (whose inherent role in improving survival is not assessed) should be therefore useful. The possible role of serum tumor markers determinations, for this purpose, is here discussed on the ground of a series of 20 patients affected by stage III ovarian carcinoma. Following this experience, a valuable role seems attributable to CA 125 in monitoring tumor response. Patients achieving values under 35 U/ml before second-look laparotomy showed tumor residuals in the range O-microscopic- < 1cm., that is, neoplastic localizations reliable for consolidation radiation therapy.
Tumour Associated Antigens CA 15.3 and CA 125 in Ovarian Cancer
Authors: Lotzniker M. , Pavesi F. , Scarabelli M. , Vadacca G. , Franchi M. , Moratti R.
Published: March 2018

CA 125 and CA 15.3 antigens were determined by enzyme immunoassay in 78 patients with ovarian cancer for a total of 540 determinations. The antigens were also investigated in sera from 100 women with other gynaecological diseases, 82 lung cancer patients and in 39 pleural fluids of varying origin. CA 15.3 reference values were evaluated in 91 healthy women (cut-off: 25 U/ml). CA 15.3 sensitivity at diagnosis (60%) and for detecting relapse (44%) was lower than that of CA 125 (90% and 64,7%, respectively). However, CA 15.3 does not increase with aspecific mesothelial cell reaction and thus it is more specific than CA 125. Combined use of the markers during follow-up improves early detection of relapse (at least one of the two was positive in 79%, of cases). Therefore both CA 15.3 and CA 125 should be routinely determined for the detection and monitoring of ovarian cancer.
Circulating Immune Complexes in Human Breast Cyst Fluids: Relationship with Intracystic Immunoglobulin and Electrolyte Levels
Authors: Mannello F. , Battistelli S. , Bocchiotti G.D. , Marcheggiani F. , Troccoli R.
Published: March 2018

Circulating immune complexes, the major classes of immunoglobulins and electrolyte concentrations were measured in sixty-two breast cyst fluids aspirated in women affected by gross cystic breast disease. Two main classes of cysts were defined according to the Na/K ratio. Appreciable levels of immunoglobulins were found in almost all samples examined; 66% of breast cyst fluids showed increased levels of immune complexes. A highly significant linear correlation between increased values of immune complexes and immunoglobulin M (p < 0.001) was found in apocrine cysts, characterized by Na/K ratio <3. However, a significant inverse linear correlation was found between positive values of immune complexes and lowered levels of immunoglobulins A (p < 0.001) and G (p < 0.001) in epithelial cysts with Na/K ratio > 3. These data suggest and confirm that the menstrual cycle can also influence or modulate the metabolic activity of human breast cells as a part of the secretory immune system. The relationship between immune complexes and immunoglobulins and electrolyte profiles may provide further knowledge about the immunological features of breast cyst fluid and suggest the possible alteration of immune-response in cystic breast lesions associated with increased cancer risk
Evaluation of a Radioreceptor Assay to Assess Exogenous Estrogen Activity in Serum of Patients with Breast Cancer
Authors: Di Lorenzo D. , Roggeri G. , Iacobello C. , Belloli S. , Gion M. , Za Va D.T. , Ghielmi S. , Albertini A.
Published: March 2018

A radioreceptor assay (RRA) for the determination of total estrogen activity, was set up and used to assess the possible presence of exogenous molecules with estrogen activity in serum; a comparison was made with the specific radioimmunoassay (RIA) for the endogenous estrogen 17-B estradiol (17-B-E2).

The assay was first performed on sera from healthy people taking estrogens in the form of oral contraceptives or lotions for local application whose total estrogenic activity in the blood was assumed to be abnormal.

The assay was then performed on serum from 98 patients with early breast cancer and 20 patients with metastasis, not undergoing hormone therapy.

A higher estrogen activity was found in 2.5% of sera compared to the activity found using the RIA method which is specific for endogenous estrogen 17-B-E2, the RRA/17-B-E2 ratio being higher than 3. Increased estrogen activity was found in 10% serum samples from digoxin treated cardiopathic patients, with an RRA/17-B-E2 ratio ranging from 4.4 to 20.

The RRA assay could prove useful for showing up exogenous estrogen activity from various sources (drugs, food) in sera of people in whom estrogen stimulation could be potentially dangerous (i.e. in patients with hormone-sensitive tumors). This exogenous activity could support a certain degree of neoplastic stimulation and, therefore, unfavourably condition the patients’ therapeutic response.
Cell Kinetics and Tumor-Associated Antigen Expression in Human Mammary Carcinomas
Authors: Contegiacomo A. , Costantini R. Mariani , Muraro R. , Battista P. , Valli C. , Frati L. , Calderopoli R. , Zilembo N. , Falco I. , Petrella G. , Bianco A.R.
Published: March 2018

Twenty-six primary breast carcinomas were studied to evaluate cell proliferation as assessed by thymidine labeling index (TLI), and antigenic phenotype, as defined by immunohistochemistry using eight monoclonal antibodies (MAbs) to tumor-associated antigens (TAAs). The majority of tumors had low TLI values. Reactivity to MAbs B72.3, CC49, CC83 (anti TAG 72), COL-12 (anti CEA) and MOv2 (against a tumor-associated mucoprotein) was restricted to < 50% of the tumors studied, while MAbs B1.1 (anti CEA), MBrl and MBr8 (to tumor-associated carbohydrates) reacted with > 50% of the cases. Correlations between expression of TAAs and proliferative activity showed that the tumors could be divided into three groups, two characterized by either high proliferative activity and absence of antigenic expression or low proliferative activity and strong antigenic expression, and the third showing no relation between these two biological features. We defined two antigenic phenotypes associated with specific cellular kinetics: one characterized by negative immunoreaction with MAbs, CC49, CC83 and COL-12 and high proliferative activity; the other characterized by intense immunoreactivity with these antibodies and low proliferative activity. The data suggest that cell proliferation and antigenic phenotype may define biologic subsets of breast carcinomas
TAF Test in Primary Esophageal Carcinoma: Comparison with other Tumor Markers
Authors: Taccone W. , Gion M. , Pecchio F. , Rapellino M. , Tremolada C. , Mione R. , Gatti C. , Ruol A. , Segalin A. , Dei Poli M. , Pedicini G.
Published: March 2018

An ELISA method for the determination of circulating specific HSV-TAA antibodies has recently become available (TAF test). The presence of TAF was tested in serum of 154 patients with primary esophageal carcinoma, collected in three institutions. The overall TAF-test positivity rate was 57.1%, being significantly lower in stage IV than in stage III patients. The concordance rate between TAF and CEA, ferritin, TPA, SCC and TATI was low, suggesting that TAF is probably independent of the other tumor markers evaluated.

The clinical role of TAF-test determination in patients with esophageal carcinoma is currently under evaluation.
Tumor Markers in Leukemia: Evaluation of Serum Levels of Different Forms of Sialic Acid, Regan Isoenzyme and Lactate Dehydrogenase
Authors: Patel P.S. , Adhvaryu S.G. , Baxi B.R.
Published: March 2018

A sensitive and specific serum marker can greatly help in the early diagnosis of malignancy as well as in monitoring the treatment of cancer patients. The present work was initiated for determining serum levels of Total Sialic Acid (TSA), Lipid Bound Sialic Acid (LSA), Free Sialic Acid (FSA), Regan Isoenzyme (RI) and Lactate Dehydrogenase (LDH), so as to evaluate their value as potential tumor markers. Fifty patients with anemia and 78 patients with leukemia were studied. The leukemia group consisted of 32 cases of Acute Myeloid Leukemia (AML), 29 cases of Chronic Myeloid Leukemia (CML) and 17 cases of Acute Lymphatic Leukemia (ALL). The levels were compared with the values obtained from 88 healthy individuals. Compared to the healthy controls, all the biomarkers were significantly elevated in patients with anemia as well as in those with leukemia. However, in leukemia patients significantly higher levels of TSA, LSA, FSA and LDH were observed compared to anemia patients. TSA levels were significantly higher in AML patients compared to CML and ALL patients. LSA levels were also significantly higher in AML patients compared to ALL patients. LSA was the most sensitive (84.6%) while FSA and RI levels were the most specific (78.0%) markers for leukemia. The combined use of the markers showed increased sensitivity and specificity (100.0% and 98.0%, respectively). The study suggested that the biomarkers investigated might be used for differentiating anemic from leukemic conditions, however, more in-depth studies are indicated to assess their utility in classifying various leukemias.
Serum Levels of Ceruloplasmin, Properdin Factor B and Copper in Lymphoma Patients
Authors: Casamassima A. , Addabbo L. , Caporusso L. , Lorusso V.
Published: March 2018

The serum levels of Ceruloplasmin (CER), Properdin Factor B (PFB) and Copper (CU) were evaluated in a series of 40 patients with Hodgkin's Disease and 46 patients with non-Hodgkin's lymphoma. Concentrations of CER and PFB were determined by rate nephelometry and CU concentrations by the bathocuproine colorimetric method. The results obtained demonstrated that CER, together with the well documented CU, can be used for monitoring Hodgkin's Disease.
Squamous Cell Carcinoma Antigen and Protein-Bound Sialic Acid in the Management of Head and Neck Cancer
Authors: Bhatavdekar J.M. , Patel D.D. , Vora H.H. , Balar D.B.
Published: March 2018

Serum squamous cell carcinoma antigen (SCCAg) and protein-bound sialic acid (PBSA) were measured in 43 head and neck cancer patients and 50 controls. SCCAg and PBSA were correlated with clinical stage, histological grade, presence/absence of keratin and disease course. Patients with advanced cancer (stage III and IV) and grade III tumors had higher PBSA levels but no such difference was observed for SCCAg. Head and neck cancer patients were grouped according to the disease status i.e. a) patients who developed recurrence and b) who responded to the adjuvant therapies. There was an excellent correlation between serial serum PBSA changes and the progression of disease or the response to therapy in patients with advanced head and neck cancer.
The Tumour Marker CA 195 in Colorectal and Pancreatic Cancer
Authors: Sagar P.M. , Taylor O.M. , Cooper E.H. , Benson E.A. , Mcmahon M.J. , Finan P.J.
Published: March 2018

The aim of this study was to measure the serum level of the tumour markers CA 195 and CEA in patients with either colorectal or pancreatic cancer both before and at serial intervals after operation. CA 195 and CEA were measured in 199 patients with colorectal cancer and 52 patients with pancreatic cancer. The median concentrations of CA 195 were 3.0 u/ml (interquartile range 3.0-4.5 u/ml) in patients with a Dukes’ stage A lesion, 5.8 u/ml (3.0-18.2 u/ml) in patients with a Dukes’ stage B lesion, 6.1 u/ml (3.0-24.7 u/ml) in patients with a Dukes’ stage C and 23.8 u/ml (11.1-409.0 u/ml) in patients with metastatic disease (normal range 0-7 u/ml). The median levels of CEA were 2.6 ng/ml (1.7-3.3 ng/ml) for Dukes’ stage A, 3.3 ng/ml (1.7-7.2 ng/ml) for Dukes’ stage B, 3.7 ng/ml (2.2-7.9 ng/ml) for Dukes’ stage C and 34.5 ng/ml (13.3-289.4 ng/ml) for metastatic disease. A rising level of CA 195 or CEA after operation suggested recurrence of the tumour. In none of these patients was the recurrence operable. In patients with pancreatic adenocarcinoma, the level of CA 195 was significantly higher in patients with metastatic disease but it did not discriminate between resectable and unresectable disease. The duration of survival correlated with the initial level of CA 195 (Rs = –0.66, p < 0.001).
Plasma Monomeric Calcitonin as a Marker of Disease Activity in Multiple Myeloma Patients with Osteolysis
Authors: Monti M. , Scazzoso A. , Bevilacqua M. , Santi I. , D'Aprile E. , Saligari A , Norbiato G. , Cunietti E.
Published: March 2018

Circulating monomeric human calcitonin (hCT-M), parathyroid hormone, osteocalcin, alkaline phosphatase, urinary hydroxyproline, corrected serum calcium and inorganic phosphate were measured in 49 multiple myeloma patients and 49 matched controls. In patients with Durie-Salmon stage III disease hCT-M levels (16.9 ± 5.8 ng/l, mean + SD) were significantly higher than controls and stage I patients (P < 0.01), and correlated directly with corrected serum calcium (r = 0.74; P < 0.001). In the same subgroup 14 of 15 patients had plasma hCT-M concentrations higher than the mean + 2SD of the controls. The calcium infusion test induced an increase of hCT-M in normocalcemic patients which was significantly greater in patients with advanced disease than in either controls or stage I patients. These findings suggest that hCT-M may be a biochemical index of bone resorption and disease activity in myeloma patients with osteolysis. In fact, its plasma concentrations were elevated in a large proportion (93%) of patients with severe bone involvement, and correlated directly with serum calcium. Moreover, our findings suggest the presence of a calcitonin-dependent calcium homeostatic mechanism, that protects against hypercalcemia due to tumor osteolysis.
The CEA Family: A System in Transitional Evolution?
Authors: Stanners C. P. , Rojas M. , Zhou H. , Fuks A. , Beauchemin N.
Published: March 2018

The CEA family consists of two structurally and functionally distinct subgroups; the group including CEA, NCA and CGM-6 which are cell surface-bound by phosphatidylinositol (PI) linkages, and the group of BGP splice variants which have transmembrane and cytoplasmic domains. Although all CEA family members mediate intercellular adhesion in vitro, the PI-linked group show Ca++ and temperature independent adhesion whereas the BGP group show rapidly reversible Ca++ and temperature dependent adhesion. From the close alignment in cDNA nucleotide sequences between family members and between repeated domains in one family member, it is apparent that the CEA family is now rapidly evolving; in fact, analogs of only the transmembrane BGP group have been found so far in the mouse. The addition of a new group of potent adhesion molecules to complex species at some time after the rodent radiation has strong evolutional implications, which are discussed.
CEA and NCA Expressed by Colon Carcinoma Cells Affect their Interaction with and Lysability by Activated Lymphocytes
Authors: Rivoltini L. , Cattoretti G. , Arienti F. , Mastroianni A. , Parmiani G.
Published: March 2018

Heterogeneous lysability by interleukin-2 activated lymphocytes (LAK) and other immune effectors was observed in the human colon-carcinoma lines LoVo/Dx, LoVo/H and HT29. The tumor cells with high susceptibility to LAK (LoVo/Dx, HT29) expressed higher amounts of the adhesion molecules ICAMl, LFA3 and NCA/CEA than cells with low LAK sensitivity (LoVo/H). Monoclonal antibodies against these molecules caused a marked reduction of lysis by LAK of LoVo/Dx and HT29. A pool of these antibodies induced a nearly complete inhibition of the LAK lysis of both lines. Treatment of LoVo/Dx with differentiating agents (dimethylformamide and retinoic acid) led to a decreased expression of the adhesion molecules, including NCA, accompanied by increased resistance to LAK-mediated lysis. Moreover, the presence of CEA soluble antigen drastically inhibited the cytotoxic activity of LAK effectors against HT29 and LoVo/Dx cells, in a dose-dependent manner. These data indicate that sensitivity of colon-carcinoma cells to activated lymphocytes depends on the level of expression of adhesion molecules, including CEA and NCA. Given the role of CEA-related antigens in tumor/lymphocyte interaction, soluble CEA, frequently released by colon-carcinoma, may be involved in immunosuppressive effects induced in vivo by tumor cells.
Immunohistology of Carcinoembryonic Antigen (CEA). Specificity of Reagents, Choice of Control Tissues and Practical Application in Surgical Pathology
Authors: Nap M. , Wilhelm W.W.
Published: March 2018

Immunohistology of CEA has been used now for many years in research and in diagnostic applications. In this congress paper, the need for specificity checks, correct preservation and quality control of antibodies as well as the choice and preservation of control tissues will be discussed and, in addition, some aspects of the interpretation of CEA immunohistology in surgical pathology are illustrated, based upon prospectively collected data from a routine surgical pathology unit. An approach for collection and analysis is demonstrated and the diagnostic importance of CEA expression together with other antigens in the same tumor.
CEA Serum Levels in Non-Neoplastic Disease
Authors: Morell A. Ruibal
Published: March 2018

Several non-neoplastic conditions, i.e., acute and chronic inflammations, benign tumors, renal or hepatic insufficiency, are associated with elevated plasma levels of Carcinoembryonic Antigen (CEA). Usually, CEA elevation in these pathologies is less than 10 ng/ml.

CEA values in non-malignant disease can be affected by many factors, which can be classified into five main categories: a) tissular, b) physiological, c) metabolic, d) circulating and e) methodological factors. Synthesis, expression and realease are the most important tissular factors. Among the metabolic ones liver, biliary and renal functions play a primary role in the determination of CEA concentrations. In addition, other factors such as the presence of circulating CEA-like substances, autoantibodies and immunocomplexes or the characteristics of the assay method can influence the diagnostic value of the CEA test.

All these factors must be carefully considered when the marker is used in clinical practice.
CEA Determination in the Follow-Up of Extracolorectal Neoplasms
Authors: Lamerz R.
Published: March 2018

CEA was initially described as a tumor and organ specific colorectal antigen, but later found by more sensitive methods in other tumors (stomach, pancreas, lung, breast) and in minor amounts in inflammatory, normal adult and fetal organs of the gastrointestinal tract. The main clinical application of CEA concerns its pretherapeutic and serial determination as circulating antigen in serum and other body fluids by means of CEA-specific, commercially available test kits. By clinical studies a significant correlation has been proven between the pretherapeutic serum CEA level and tumor stages and prognosis. Moreover, serial CEA level changes have been shown a valuable monitor following operation or during radio/chemotherapy anticipating and reflecting the clinical course of disease. In combination with newly established tumor markers, the main clinical indication for CEA determination in addition to colorectal cancer concerns monitoring of patients with stomach (+ CA 72-4), lung (+ NSE/SCC) and breast cancer (+ CA 15-3/MCA).
Cancer Imaging with CEA Antibodies: Historical and Current Perspectives
Authors: Goldenberg D.M.
Published: March 2018

This article reviews the history and status of cancer imaging with radiolabeled antibodies against carcinoembryonic antigen (CEA). Although CEA and many other cancer-associated antigens are not distinct for neoplasia, the quantitative increase of these markers in malignant tissues provides a sufficient differential for selective antibody targeting. Animal studies with xenografted human tumors provided the first evidence of the prospects of this technology, followed by initial clinical success with purified goat whole IgG antibodies to CEA, labeled with 131I and with the use of dual-isotope subtraction methods. Subsequently, improved and earlier imaging could be accomplished with monoclonal antibody fragments, which then would permit the use of shorter-lived radionuclides, such as 111In, 123I, and 99mTc. The preferred use of a monoclonal anti-CEA IgG Fab' fragment, labeled with 99mTc by a recently developed, simple and rapid kit, has enabled the detection of small lesions, including those in the liver, within 4 h of injection. By means of SPECT imaging, a high sensitivity and specificity for RAID could be achieved.
Diagnostic Applications and Therapeutic Approaches with Different Preparations of Anti-CEA Antibodies
Authors: Delaloye A. BISCHOF , Delaloye B.
Published: March 2018

Various preparations of anti-CEA antibodies have shown to detect very sensitively CEA producing tumors. The development of human anti-mouse antibodies (HAMA) prevents from the widespread use of immunoscintigraphy (IS) in the follow-up of patients with colorectal carcinoma. It is, however, not yet clear if genetically reshaped antibodies will solve this problem and it is even less clear if this will change prognosis of these patients. There is certainly room for new therapeutic approaches in colorectal carcinoma. Radioimmunotherapy in combination with other techniques might advantageously complete surgery, chemotherapy and radiotherapy, but needs to be further developed.
Anti-CEA and Other Antibodies in the Study of Gastrointestinal Tumors
Authors: Lastoria S. , Caracò C. , Vergara E. , Castelli L. , Salvatore M.
Published: March 2018

Localization of gastrointestinal tumors by means of labeled monoclonal antibodies is a new, sensitive and suitable technique currently used in several centers. Encouraging results have been documented with several monoclonal antibodies by different authors. This article reviews our experience with radioimmunoscintigraphy in 59 patients with colorectal cancer in follow-up, using 131I and 111In labeled B72.3, and in 16 patients with primary gastrointestinal tumors using 99mTc anti-CEA monoclonal antibody (type F023C5). The sensitivity of both B72.3 and anti-CEA was greater than 70% either for primary tumors and abdominal recurrences or distant metastases except hepatic ones. A significant gradient in antibody uptake was measured on surgical biopsies between tumors and normal tissues allowing a good in vivo contrast for gamma detection. We have defined the impact of some factors affecting in vivo tumor targeting. In fact, pharmacodynamics of MAbs, percentage of injected dose bound to tissues were measured, and in particular antigenic content in tumor nodules was quantified. Furthermore, the results of RIS were compared to those obtained by CT and other imaging modalities.
Serum Prolactin Levels in Women with Gross Cystic Breast Disease
Authors: Vizoso F. , Allende M.T. , García-Muñiz J.L. , Alexandre E. , Fueyo A. , Ruibal A.
Published: March 2018

Serum prolactin (PRL) concentrations at baseline and after TRH stimulation were determined in 15 healthy women and in 51 premenopausal patients suffering from Gross Cystic Breast Disease. All women were in the luteal phase of the menstrual cycle and patients were divided into three groups according to cyst type at presentation. Basal hormone levels were within the normal range in the control group and in the three cystic breast disease groups. The maximum PRL response to TRH stimulation was significantly higher (p < 0.001) in patients with type I cysts (low Na+/K+ intracystic ratio and apocrine epithelium) than in patients with type II cysts (high Na+/K+ intracystic ratio and flattened epithelium), type III cysts (intermediate Na+/K+ intracystic ratio and mixed epithelium) and in normal women. Serum PRL concentrations corresponding to samples obtained 60 and 90 minutes after stimulation remained higher in the first group of patients. These results led us to consider the existence of an altered central regulation of PRL secretion in patients with type I cysts at presentation.
Tissue Polypeptide Antigen (TPA) in Chronic Active Hepatitis and Mild Liver Diseases
Authors: Collazos J. , Genollà J. , Ruibal A.
Published: March 2018

Tissue polypeptide antigen (TPA) is a non-specific tumor marker with a broad reactivity. Increases in TPA are also observed in benign liver diseases. We conducted this study to evaluate the usefulness of TPA serum level determination in 15 patients with chronic active hepatitis (CAH) and in 30 patients with mild liver diseases (MLD) diagnosed at the time of evaluation. TPA levels were abnormal in 73.3% of CAH patients and in 40% of MLD patients. CAH patients had significantly higher TPA levels than MLD patients (p = 0.006). There was a significant correlation between TPA and ASAT(r = 0.581 p < 0.00001), suggesting that cytolysis plays an important role in the increase in TPA. A TPA value of twice the normal level will unlikely be due to MLD (specificity 90%). TPA can be used in the clinical characterization of these patients and in the selection of patients for biopsy.