[The expressions and diagnostic values of miR-18a and miR-21 in esophageal cancer].

Objective: To investigate the expressional levels and diagnostic values of miR-18a and miR-21 in esophageal carcinoma. Methods: The expressions of miR-18a and miR-21 in esophageal cancer tissues and adjacent tissues from 45 esophageal cancer patients, peripheral blood from 45 esophageal cancer patients and 50 healthy donors respectively were detected by RT-PCR. The expressions of miR-18a and miR-21 in normal esophageal epithelial cell HET-1A, esophageal cancer cell lines including ECA109, KYSE150 and TE1 were also detected. Chemiluminescence immunoassay was used to quantitatively detect the concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), CYRFA21-1 and TPA (tissue polypeptide antigen) in peripheral blood serum from esophageal cancer patients and healthy controls. Meanwhile, the diagnostic effects of miR-18a and miR-21 on esophageal cancer were compared with those of tumor markers in serum. Results: The expression levels of miR-18a and miR-21 in esophageal cancer cells ECA109, KYSE150 and TE1 were 1.64±0.17, 1.62±0.19, 1.46±0.12 and 20.52±1.48, 6.73±0.73, 1.43±0.19, respectively, higher than those in normal esophageal epithelial cells (both P<0.01). The expressions of miR-18a and miR-21 in esophageal cancer tissues were 32.48±28.62 and 8.67±11.98, respectively, significantly higher than those in adjacent tissues (all P<0.001). The expression levels of miR-18a and miR-21 in peripheral blood of patients with esophageal cancer were 12.66±11.92 and 9.15±8.14, respectively, significantly higher than those in the normal control group (both P<0.001). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve of miR-18a and miR-21 for diagnosis of esophageal cancer were 0.948 and 0.913 5, respectively. Compared with traditional esophageal tumor markers, the expressions of miR-18a and miR-21 were more sensitive in the diagnosis of esophageal cancer. The sensitivity and accuracy of the expressions of miR-18a and miR-21 combined with traditional esophageal tumor markers in diagnosis of esophageal cancer can be further improved to 97.8% and 68.4%, respectively. Conclusion: Our study reveals that the expressions of miR-18a and miR-21 play important roles in the diagnosis of esophageal cancer and may be potentially novel biomarkers.

Criteria to interpret cancer biomarker increments crossing the recommended cut-off compared in a simulation model focusing on false positive signals and tumour detection time.

BACKGROUND: Several criteria have been proposed to interpret increments in serological cancer biomarker concentrations starting from low baseline concentrations crossing the cut-off. None of the criteria have been compared for their ability to signal tumour growth when ≤2% false positive results are accepted. METHODS: The cancer biomarker Tissue Polypeptide Antigen was used as an example. Seven criteria to interpret increments in concentrations were investigated by computer simulations. Firstly, for each criterion, we identified a baseline concentration stratified for three levels of biological variation providing ≤2% false positive signals of tumour growth during one year of monitoring. Secondly, combining the steady state concentrations with rates of marker increase during tumour growth allowed calculation of the lengths of tumour detection times for each criterion. RESULTS: The number of false positive marker signals depended on the baseline concentration, the magnitude of biological variation, and the magnitude of the required increment defined in the criterion. The lengths of the tumour detection times also depended on the rates of marker increase. CONCLUSIONS: The results suggest that different types of criteria should be used within different intervals of below cut-off level concentrations if the rate of false positive signals of marker increments should be kept ≤2%.

A sandwich-type immunosensor using Pd-Pt nanocrystals as labels for sensitive detection of human tissue polypeptide antigen.

A sandwich-type immunosensor was developed for the detection of human tissue polypeptide antigen (hTPA). In this work, a graphene sheet (GS) was synthesized to modify the surface of a glassy carbon electrode (GCE), and Pd-Pt bimetallic nanocrystals were used as secondary-antibody (Ab2) labels for the fabrication of the immunosensor. The amperometric response of the immunosensor for catalyzing hydrogen peroxide (H2O2) was recorded. And electrochemical impedance spectroscopy was used to characterize the fabrication process of the immunosensor. The anti-human tissue polypeptide antigen primary antibody (Ab1) was immobilized onto the GS modified GCE via cross-linking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide (EDC/NHS). With Ab1 immobilized onto the GS modified GCE and Ab2 linked on Pd-Pt bimetallic nanocrystals, the immunosensor demonstrated a wide linear range (0.0050-15 ng ml(-1)), a low detection limit (1.2 pg ml(-1)), good reproducibility, good selectivity and acceptable stability. This design strategy may provide many potential applications in the detection of other cancer biomarkers.

Prognostic significance of TPA versus SCC-Ag, CEA and neopterin in carcinoma of the uterine cervix.

INTRODUCTION: Prognostic significance of squamous cell carcinoma antigen (SCC-Ag), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA) and neopterin in cervical cancer patients was compared. MATERIALS AND METHODS: Pretreatment concentrations were determined in 138 women. RESULTS: Median age was 52 years, 85% squamous cell carcinomas, 15% adeno- or adenosquamous carcinomas were seen. In 36% Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage I, 24% stage II, 32% stage III and 8% stage IV was diagnosed. TPA was elevated in 22%, SCC in 68%, CEA in 42% and neopterin in 29%. These patients showed significantly worse overall survival in univariate analysis (p<0.001). TPA remained as independent prognostic factor in multivariate analysis. CONCLUSIONS: Elevation of TPA was associated with worse overall survival.

Tumor markers in pleural effusions.

AIM: The aim of this study was to determine the diagnostic capabilities of tumor markers in pleural effusion and their importance for assessment of the etiology of pleural effusions. PATIENTS AND METHODS: In pleural effusions from 166 patients hospitalized during the period 2003-2005 at the Department of Oncology and Radiotherapy, Faculty Hospital in Pilsen, the following tumor markers were determined: thymidine kinase (TK), neuron-specific enolase (NSE), cytokeratins [tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and cytokeratin fragment 19 (CYFRA 21-1)], carcinoembryonic antigen (CEA) and mucinous markers (CA 15-3, CA 19-9, CA 125). The inflammatory marker procalcitonin-PCT was also assessed. RESULTS: Tumor markers CA 125, TPA, TPS were significantly elevated in exudates, irrespective of the etiology, as a non-specific reaction in mesothelial cells. TK had a sensitivity of over 80% for all the types of cancer examined, while CA 15-3 had a sensitivity of over 90%. CONCLUSION: Significant positivity of PCT and CA 15-3 in pleural effusions indicate a suspicion of inflammatory disease. Positivity of TK and CA 15-3 indicate a strong suspicion of malignant exudates.

Modelo experimental de fotoenvejecimiento cutáneo por radiación ultravioleta A / Experimental model of UVA-induced cutaneous photoageing

Antecedentes: La piel puede sufrir, además del envejecimiento cronológico, el fotoenvejecimiento, secundario a las radiaciones ultravioletas, las cuales se consideran el carcinógeno ambiental más potente. Material y métodos: Hemos utilizado 32 ratones Swiss en 4 grupos: I. control; II. TPA (102 sesiones); III. UVA (102 sesiones, 120 minutos/sesión); IV. TPA y UVA (32 sesiones, 120 minutos/sesión). Al final realizamos la necropsia. La piel del lomo y orejas fueron incluidas en parafina por el método habitual, seccionadas a 5 μm y teñidas con H.E. Valoramos diversos criterios histológicos epidérmicos y dérmicos (+, ++ o +++), por dos observadores distintos. Resultados: Hemos establecido un modelo de fotoenvejecimiento en los dos grupos tratados con UVA que presentaban lesiones de displasia moderada a severa en el grupo irradiado con UVA y carcinomas invasores en el grupo con UVA y TPA, mientras que en el grupo de TPA sólo observamos múltiples áreas de hiperplasia epitelial. Conclusiones: La exposición crónica a UVA asociada al promotor tumoral TPA ha desarrollado un modelo de fotocarcinogénesis cutánea en ratones Swiss

Introduction: Chronological ageing aside, skin may also experience photoageing as a result of exposure to ultraviolet radiation, considered to be the most potent environmental carcinogen. Materials and Methods: 32 Swiss mice (divided into 4 groups) were treated as follows: I (Control); II (TPA: 102 sessions); III (UVA: 102 sessions at 120 minutes/session); IV (TPA & UVA: 32 sessions at 120 minutes/session). Finally, necropsies were performed. The skin from the back and ears was included in paraffin via the usual method, sectioned at 5 μm and stained using H-E. Diverse dermal and epidermal histological criteria were evaluated (+, ++, +++), by two different observers. Results: A model for photoageing was established for both groups treated with UVA, which displayed moderate to severe dysplasia in the case of those treated with UVA alone and invasive carcinoma in the case of those treated with UVA and TPA, whilst only (multiple) areas of epithelial hyperplasia were observed in the group treated with TPA alone. Conclusions: Chronic exposure to UVA in conjunction with the tumour promoter TPA has provided a model for cutaneous photocarcinogenesis in Swiss mice

Modelo experimental de fotoenvejecimiento cutáneo por radiación ultravioleta A / Experimental model of UVA-induced cutaneous photoageing

Antecedentes: La piel puede sufrir, además del envejecimiento cronológico, el fotoenvejecimiento, secundario a las radiaciones ultravioletas, las cuales se consideran el carcinógeno ambiental más potente. Material y métodos: Hemos utilizado 32 ratones Swiss en 4 grupos: I. control; II. TPA (102 sesiones); III. UVA (102 sesiones, 120 minutos/sesión); IV. TPA y UVA (32 sesiones, 120 minutos/sesión). Al final realizamos la necropsia. La piel del lomo y orejas fueron incluidas en parafina por el método habitual, seccionadas a 5 μm y teñidas con H.E. Valoramos diversos criterios histológicos epidérmicos y dérmicos (+, ++ o +++), por dos observadores distintos. Resultados: Hemos establecido un modelo de fotoenvejecimiento en los dos grupos tratados con UVA que presentaban lesiones de displasia moderada a severa en el grupo irradiado con UVA y carcinomas invasores en el grupo con UVA y TPA, mientras que en el grupo de TPA sólo observamos múltiples áreas de hiperplasia epitelial. Conclusiones: La exposición crónica a UVA asociada al promotor tumoral TPA ha desarrollado un modelo de fotocarcinogénesis cutánea en ratones Swiss

Introduction: Chronological ageing aside, skin may also experience photoageing as a result of exposure to ultraviolet radiation, considered to be the most potent environmental carcinogen. Materials and Methods: 32 Swiss mice (divided into 4 groups) were treated as follows: I (Control); II (TPA: 102 sessions); III (UVA: 102 sessions at 120 minutes/session); IV (TPA & UVA: 32 sessions at 120 minutes/session). Finally, necropsies were performed. The skin from the back and ears was included in paraffin via the usual method, sectioned at 5 μm and stained using H-E. Diverse dermal and epidermal histological criteria were evaluated (+, ++, +++), by two different observers. Results: A model for photoageing was established for both groups treated with UVA, which displayed moderate to severe dysplasia in the case of those treated with UVA alone and invasive carcinoma in the case of those treated with UVA and TPA, whilst only (multiple) areas of epithelial hyperplasia were observed in the group treated with TPA alone. Conclusions: Chronic exposure to UVA in conjunction with the tumour promoter TPA has provided a model for cutaneous photocarcinogenesis in Swiss mice

Neuron-specific enolase is an effective tumour marker in non-small cell lung cancer (NSCLC).

BACKGROUND: Neuron-specific enolase (NSE) is a well known marker of small cell lung cancer. The present study was designed to assess the clinical value of NSE in non-small cell lung cancer (NSCLC), as compared to that of carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA). METHODS: The study comprised 448 new consecutive NSCLC patients seen from 1996 to 2001. A set of 30 anthropometric, clinical, physical, laboratory, radiological, and pathological variables was prospectively recorded for all patients. Patients were carefully followed-up, and their subsequent clinical course recorded. RESULTS: Increased values of NSE were present in 32% of the patients. Bivariate analyses showed that NSE, TPA and CEA were significantly correlated with each other, lactate dehydrogenase, tumour diameter, and disease extent. Univariate analyses showed that patients with elevated concentration of both NSE and TPA had significantly shorter survivals than patients with low values (30 [95% CI: 25-35] vs. 61 weeks [46-76], and 30 [CI: 24-36] vs. 59 weeks [40-79], respectively, P=0.0000). The Cox proportional hazards model including all the 22 variables significant in univariate analysis selected, in decreasing order of significance, the following variables: (1) N factor; (2) main treatment; (3) ECOG PS; (4) CNS metastasis; (5) age; (6) tumour cavitation; (7) NSE; (8) T factor; and (9) adrenal gland metastasis. CONCLUSIONS: This data indicates that serum assay of NSE is a useful marker also in NSCLC and a significant predictor of survival, independently of the other prognostic factors.

Comparative analysis of CA125, tissue polypeptide specific antigen, and soluble interleukin-2 receptor alpha levels in sera, cyst, and ascitic fluids from patients with ovarian carcinoma.

BACKGROUND: The serum markers CA125, tissue polypeptide specific antigen (TPS), and soluble interleukin-2 receptor alpha (sIL-2Ralpha) concentrations were determined in sera, cyst, and ascitic fluids from patients with malignant and benign ovarian neoplasms. METHODS: CA125, TPS, and sIL-2Ralpha concentrations were measured in sera, cyst, and ascitic fluids by immunoassays in 67 patients with carcinoma and in 32 patients with benign ovarian neoplasms. RESULTS: CA125, TPS, and sIL-2Ralpha levels were elevated significantly in sera from patients who had ovarian carcinoma compared with patients who had benign neoplasms (P < 0.001). Patients who had International Federation of Gynecology and Obstetrics (FIGO) Stage III-IV disease had significantly higher serum levels for the markers studied compared with patients who had FIGO Stage I-II disease (P < 0.001 for CA125; P = 0.02 for TPS and sIL-2Ralpha). Concurrent measurement of CA125 and sIL-2Ralpha in sera identified 100% of ovarian carcinomas in FIGO Stage I-II. All patients with carcinoma demonstrated markedly higher levels of CA125 and TPS for both cyst and ascites compared with corresponding sera (P < 0.001). The level of sIL-2Ralpha was higher statistically in ascitic fluid compared with the level in serum (P < 0.001); however, its values in sera and cyst fluids were comparable. In ascitic fluid, the CA125 level was significantly higher in patients who had FIGO Stage III-IV disease compared with patients who had FIGO Stage I-II disease (P = 0.002), whereas such correlations were not found for TPS or sIL-2Ralpha. In cyst fluids, the levels of all studied markers were independent of the FIGO stage. In cyst fluids from patients with benign ovarian neoplasms, TPS and sIL-2Ralpha levels were significantly lower compared with the levels in patients with ovarian carcinoma (P < 0.001), whereas the values of CA125 were overlapping. CA125 and TPS concentrations were higher in cyst fluids compared with corresponding sera, whereas sIL-2Ralpha levels were comparable and low in cyst fluids and in the circulation of patients with benign neoplasms. CONCLUSIONS: In patients with ovarian carcinoma, TPS and CA125 concentrations were significantly higher in the place of their generation compared with the concentrations in blood circulation. sIL-2Ralpha values were higher in ascites compared with the values in corresponding sera, and its concentrations in sera and cyst fluids were comparable. The assessment of serum sIL-2Ralpha levels showed potential complementary value to CA125 for the detection of ovarian carcinoma in early FIGO stages; however, a 9% false positive rate limited the significance of cumulative value for a combination of these circulating markers.

Diffuse pagetoid squamous cell carcinoma of the esophagus combined with choriocarcinoma and mucoepidermoid carcinoma: an autopsy case report.

Esophageal squamous cell carcinoma in situ (SCCIS) with diffuse pagetoid features is a recently recognized rare variant of squamous cell carcinoma. A histopathological study of a specimen from a 70-year-old male Japanese patient is reported. The patient died of respiratory failure due to rapidly progressing metastatic pulmonary tumors of unknown origin 73 days after the onset of hemosputum. Autopsy disclosed widespread metastasis of choriocarcinoma in the absence of tumors of the testes or other common sites of germ cell tumors. Elevation of human chorionic gonadotropin (hCG-beta) levels was later detected in the stored serum. Serial histological evaluation of the entire esophagus revealed a small primary site of choriocarcinoma in a background of diffuse SCCIS, mainly of pagetoid type, accompanied by several small foci of submucosally invasive squamous cell carcinoma and primary mucoepidermoid carcinoma. These stimulated nodal metastasis independently of the choriocarcinoma. The SCCIS did not alter the gross mucosal appearance. This is the first reported case of diffuse pagetoid SCCIS combined with choriocarcinoma. Morphological findings and previous studies suggest that the extensive SCCIS of the esophagus resulted from pagetoid spread of tumor cells. The invasive squamous cell carcinoma, mucoepidermoid carcinoma and choriocarcinoma are suggested to have originated from the overlying SCCIS.

SPan-1 and exocrine pancreatic carcinoma. The clinical role of a new tumor marker.

AIMS OF THE STUDY: Considerable progress has been made in imaging techniques over the past few years, yet this has not resulted in the ability to reach an earlier diagnosis of exocrine pancreatic cancer. The search for a noninvasive diagnostic tool capable of early diagnosis has led to the development of a series of serum tumor markers. This article discusses the clinical evaluation of SPan-1 and its comparison with established markers such as CA 19.9, CEA, TPA and CA 242. METHODS: The markers were measured in preoperative serum samples collected from 46 patients who had undergone surgery for ductal carcinoma of the pancreas, 20 patients with chronic pancreatitis, and 23 patients with other digestive neoplasms. RESULTS: The sensitivity, specificity and diagnostic accuracy for pancreatic cancer were as follows: [table: see text] CONCLUSIONS: The antigenic determinant SPan-1, recognized by monoclonal antibodies, is elevated in sera of patients with exocrine pancreatic cancer. SPan-1 may be considered as an additional useful and reliable serum marker for the detection of this neoplasm, but it does not significantly improve the diagnostic accuracy obtained with CA 19.9.

[Study of the cytosolic concentrations of the tissue poly-peptide specific (TPS) antigen in infiltrating ductal carcinomas of the breast. Positive relationship with hormone dependency and negative with cellular proliferation]. / Estudio de las concentraciones citosolicas del antígeno polipeptídico específico tisular (TPS) en carcinomas ductales infiltrantes de mama. Relación positiva con la hormonodependencia y negativa con la proliferación celular.

INTRODUCTION: The tissue-specific polypeptide antigen (TPS) is an epitope of the tissue polypeptide antigen (TPA) which is defined by the M3 monoclonal antibody and is related to cytokeratin 18. Several groups have demonstrated its value as a useful parameter in the follow-up of some tumors. This work has aimed to study the TPS cytosolic levels in infiltrating ductal carcinomas of the breast (IDC) and their possible correlations with other clinical-biological parameters. PATIENTS AND METHODS: The TPS was determined by means of an immunoradiometric assay (Beki Diagnostics. Sweden). Other parameters included in the study were the estrogen receptors (ER), progesterone receptors (PR), pS2, cathepsin D, tissue-type plasminogen activator (t-PA), tumor size, axillary lymph node involvement, distant metastases, histological grade, ploidy and S-phase. RESULTS: The TPS cytosolic levels ranged from 1.8 to 606.3 KU/mg prt. (median 110.2) and had a significant correlation with the ER (r: 0.721), PR (r: 0.287), cathepsin D (r: 0.550) and t-PA (r:0.436). The TPS positive (> 110.2 KU/mg prt.) carcinomas had higher levels of ER (p: 0.001), PR (p: 0.021), pS2 (p: 0.058), cathepsin D (p: 0.000) and t-PA (p: 0.053) than the TPS negative tumors. When the IDC were classified according to S-phase values, we observed that the positive cases (S-phase > 8.1%, which represents the median value of all carcinomas) had lower levels of TPS (p: 0.046) than the negative tumors. Likewise, the GoG1 cellular fraction correlated positively and significantly with the TPS cytosolic levels (p: 0.000). CONCLUSIONS: Based on our results, we suggest that there is a positive correlation between the TPS cytosolic levels and hormone-dependence parameters, as well as an inverse correlation between these and the cellular proliferation parameters. Based on the above, we consider that it is worthwhile to carry out further studies on cytosolic TPS in order to investigate its possible value as a prognostic parameter in breast carcinomas.

Tissue polypeptide specific antigen (TPS), a marker for differentiation between pancreatic carcinoma and chronic pancreatitis. A comparative study with CA 19-9.

BACKGROUND: The value of serum tissue polypeptide specific antigen (TPS) as a complement to CA 19-9 in the detection of pancreatic carcinoma was determined prospectively. TPS and CA 19-9 levels obtained at the time of diagnosis in patients suspected of having chronic pancreatitis or pancreatic carcinoma were evaluated in receiver operating characteristic (ROC) curve analysis. METHODS: Serum TPS and CA 19-9 levels were measured by immunoassays in 122 subjects, 48 with pancreatic carcinoma and 74 with chronic pancreatitis. RESULTS: Elevated levels of CA 19-9 were detected preoperatively in 70% of pancreatic carcinoma patients and in 19% of chronic pancreatitis patients. Elevated levels of TPS were detected in 100% of patients with pancreatic carcinoma and in 22% of patients with chronic pancreatitis. The median levels of TPS and CA 19-9 for pancreatic carcinoma were significantly higher than those for chronic pancreatitis (P < 0.0001). Increasing the upper reference value of TPS allowed for better discrimination between chronic pancreatitis and pancreatic carcinoma. ROC curve analysis showed that the introduction of 200 U/L as a decision criterion for TPS did not reduce its sensitivity but significantly improved its specificity. At a specificity of 98% for TPS, discrimination between pancreatic carcinoma and chronic pancreatitis was found to be 97%. Increasing the upper reference level for CA 19-9 to attain a specificity of 98% decreased its sensitivity from 70% to 33%. CONCLUSIONS: At an elevated cut-off level for TPS (200 U/L), almost complete discrimination between pancreatic carcinoma and chronic pancreatitis was obtained. TPS will be more useful than CA 19-9 in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis.

An evaluation of tissue polypeptide antigen (TPA) in the two bronchoalveolar lavage fractions of lung cancer patients.

BACKGROUND: It has been proven that cytokeratins (CKs) are useful tumor markers for the follow-up, treatment monitoring and prognosis evaluation of lung cancer and among these, tissue polypeptide antigen (TPA) plays an important role. Nevertheless, only a small number of studies have been reported about their diagnostic capacity. Bronchoalveolar lavage (BAL) can be divided into two fractions: bronchiolar (BF) and alveolar (AF). For the above reasons, our aims were (1) to analyze the diagnostic usefulness of TPA in the BAL of lung cancer patients and (2) to observe if, in lung cancer patients, TPA levels in the two BAL fractions are different. This should mean that the study of tumor markers in the BAL should be carried out in both fractions to increase their diagnostic capacity. METHODS: We studied 289 BALs divided into two phases. In phase I, TPA was analyzed in the BAL of six groups of subjects (healthy persons, chronic bronchitis, asthma, respiratory infections, diffuse interstitial pulmonary diseases and lung cancer). In phase II, TPA was studied in both BAL fractions of a group of patients with lung cancer. RESULTS: We observed that TPA levels were significantly higher in the BAL of patients with bronchogenic neoplasias. In these patients, TPA was increased in the BF of the lavage in relation to the AF. In smoker patients with pulmonary carcinomas, TPA was higher in the AF of the BAL than in the lavage of non-smokers. This did not occur in the BF. We found no relation between the TPA concentrations and cancer histology. CONCLUSIONS: We believe that TPA is a useful tumor marker with diagnostic capacity and this capacity is increased when it is studied in the two BAL fractions. Smoking habit may play a role in the secretion of tumor markers by the tumor cells.

Application of tumor markers CEA, TPA, and SCC-Ag in patients with low-risk FIGO stage IB and IIA squamous cell carcinoma of the uterine cervix.

OBJECTIVE: The aim of this study was to determine the potential clinical utility of tumor markers carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) in patients with FIGO stage IB and IIA squamous cell carcinoma of the uterine cervix with low-risk clinicopathologic factors (negative lymph node metastasis, no lymphovascular space involvement, no bulky tumor size, no parametrial invasion, no deep stromal invasion, and well-differentiated cellular histology). METHODS: A retrospective study was performed on 558 patients with FIGO stage IB-IIA and pathology-proven invasive squamous cell carcinoma of the uterine cervix, treated at the Veterans General Hospital, Taipei, between December 1986 and November 1990. Serum specimens were drawn before operation. A total of 140 assessable patients were enrolled into the study (including 109 stage IB patients and 31 stage IIA patients; all patients had no clinicopathologic risk factors and had at least one tumor marker datum). Survival curves were constructed according to the Kaplan-Meier method and survival curves were compared using the log-rank test. RESULTS: In univariate analysis of survival, CEA, TPA, and SCC-Ag all have roles in the prediction of prognosis. In Cox proportional hazards model using CEA, TPA, and SCC-Ag as covariates, TPA demonstrated the most significant risk factor (P = 0.031). CONCLUSIONS: We concluded that preoperative evaluation of serum TPA might be of great value in the prediction of survival of patients without any clinicopathologic risk factors and this special group of patients should be paid much attention in the follow-up period. From this study, preoperative elevation of TPA defines a group of otherwise low-risk invasive cervical cancer patients who are at high risk for recurrence. Adjuvant therapy might be necessary for this special subset of patients. A prospective study with a larger sample should be conducted to prove this particular finding.

CA 15-3, ceruloplasmin and tissue polypeptide specific antigen as a tumour marker panel in breast cancer.

BACKGROUND: Tumour markers along with other tests, may be useful in the assessment of the prognosis, monitoring response to treatment and early detection of metastases in breast cancer. The most commonly used breast cancer antigen is CA 15-3. OBJECTIVE: To examine the value of CA 15-3, ceruloplasmin and tissue polypeptide specific antigen (TPS) panel in the monitoring of breast cancer. SUBJECTS: Serum concentrations of CA 15-3, ceruloplasmin and TPS were measured in 90 women: Fifteen controls, sixteen patients with benign breast disease (BBD), thirty one patients in remission and twenty eight patients with active breast cancer. RESULTS: The results of CA 15-3, ceruloplasmin and TPS estimates were separated into four groups. The patients not in remission were found to have significantly higher levels of CA 15-3 (p<0.0001) and ceruloplasmin (p<0.0001) compared with the other three groups. The difference between the patients in remission, BBD and the control group was not statistically significant (p>0.05) for CA 15-3 and ceruloplasmin. The difference for TPS between the patients in remission and the patients with active breast cancer was not statistically significant (p>0.05). The sensitivities of CA 15-3, ceruloplasmin, and TPS for detecting active breast cancer were 75.0%, 75.0%, and 78.0%, respectively. CONCLUSION: The highest sensitivity for active breast cancer detection was obtained by the combined use of three tumour markers. We concluded that there may be an advantage in using panels in the follow up of breast cancer patients, although so far such tests have too low a specificity to be of practical value in screening.

CYFRA 21-1, TPA-M, TPS, SCC-Ag and CEA in patients with squamous cell lung cancer and in chemical industry workers as a reference group.

In etiology of lung cancer chemical carcinogenesis seems to be a very important factor. In the studies presented here the diagnostic usefulness of tumor markers in lung cancer was evaluated, using as a reference group workers of a chemical plant producing chromite and chromate pigments. The investigations of CYFRA 21-1, TPA-M, TPS, CEA and SCC-Ag were performed before treatment in a group of 76 squamous cell lung cancer patients in different stages of disease and in a reference group of 75 workers of the chemical company, who had been exposed to hexavalent chromium for longer than 1 year and had no clinical or radiological symptoms of lung diseases. In the squamous cell lung cancer group concentrations of all analyzed tumor markers were considered to be significantly higher than in the reference group. TPA assay demonstrated higher diagnostic performance than CYFRA 21-1 and the remaining tumor markers. At 0.95 specificity, the sensitivity of TPA was 0.79, CYFRA 21-1 -0.76, of TPS -0.29 whilst of CEA and SCC-Ag -0.31. The univariate analysis showed a significant prognostic value for clinical stages, only for CYFRA 21-1 and SCC-Ag. A significant relationship between marker level and survival was observed for CYFRA 21-1 as well as SCC-Ag levels. In a multivariate analysis CYFRA 21-1 and/or TPS remained significant predictors of survival.

[Diagnostic value of the tumor markers TPA-M, CYPFRA 21-1 and CEA in pleural effusion. Prospective comparison of thoracoscopic investigations in patients with pleural effusion]. / Diagnostischer Wert der Tumormarker TPA-M, CYFRA 21-1 und CEA bei Pleuraergüssen. Prospektiver Vergleich bei thorakoskopisch untersuchten Patienten mit Pleuaerguss.

The diagnostic value of tumour markers in pleural effusion is not yet clearly defined. CEA (Carcinoembryonic Antigen), CYFRA 21-1 (Cytokeratin 19-Fragment) and TPA-M, a new monoclonal-based radioimmunoassay for TPA (Tissue Polypeptide Antigen), were measured in pleural fluid and sera of 125 consecutive patients who underwent medical thoracoscopy. The group consisted of 79 patients with malignant and 45 with non-malignant pleural effusion and 1 patient without definitive diagnosis, and hence 124 patients were available for assessing the diagnostic value. In pleural fluid based on a specificity of 90% versus benign diseases the sensitivity for CEA was 52.5%; with the maximum achievable specificity of 80% for CYFRA 21-1 the sensitivity was 68% and for TPA-M with 67% the sensitivity was 67%. Based on the cut-off values for these specificities the combined use of the three tumour markers resulted in a sensitivity of 85.7% but with a lower specificity of 59.1%. There is only a limited value for tumour markers in the diagnosis of pleural effusion.

Prognostic value of the serum tumour markers Cyfra 21-1 and tissue polypeptide antigen in malignant mesothelioma.

In malignant mesothelioma, survival is claimed to be related to age, duration of symptoms, performance status, histological subtype, stage and platelet count. However the exact prognostic value of these factors is still a matter of debate. We studied the two cytokeratin markers, Cyfra 21-1 and Tissue polypeptide antigen (TPA) for their significance in predicting survival retrospectively in 52 patients. Cyfra 21-1 and TPA were elevated in 26 (50%) and 30 (58%) patients, respectively, and were highly correlated (r = 0.98). Univariate analysis of data from 51 patients, showed a relation with survival for performance status (P = 0.010), thoracic pain (P = 0.014), platelet count (P = 0.027), Cyfra 21-1 (P = 0.002) and TPA (P = 0.003). Multivariate analysis identified independent prognostic significance for performance status, platelet count and Cyfra 21-1. In addition to performance status ( < 80 vs. > 80) the cytokeratin markers identified patients with good prognosis in a log rank test. Values of Cyfra 21-1 and TPA are significantly correlated.