Serum Tissue Polypeptide Antigen Levels Research Articles

Correlation of Serum CA242, CA724, and TPA Levels with Clinicopathological Features and Prognosis in Patients with Inflammatory Bowel Disease Complicated with Rectal Cancer.

Objective To investigate the correlation of serum cancer antigen 242 (CA242), cancer antigen 72-4 (CA724), and tissue polypeptide antigen (TPA) levels with clinicopathological features and prognosis in patients with inflammatory bowel disease (IBD) complicated with rectal cancer. Methods The data of 120 patients with IBD were retrospectively analyzed. Patients were divided into the IBD group (without rectal cancer, n = 60) and the rectal cancer group (with rectal cancer, n = 60), and 60 healthy individuals receiving medical examination during the same period were selected as the healthy group. Serum CA242, CA724, and TPA levels of research subjects were measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the clinical data of the patients were collected. The patients were followed up for 3 years and divided into the survival group and the dead group. The relationship between the levels of CA242, CA724, TPA, and prognosis was tested. Results Significant differences were found in the serum CA242, CA724, and TPA levels among three groups (P < 0.001). CA242 was related to tumor size, histological stage, growth mode, and TNM stage in patients with IBD and rectal cancer. CA724 was related to histological stage, growth mode, depth of tumor invasion (T stage), lymph node metastasis (N stage), distant metastasis (M stage), and TNM stage in patients with IBD and rectal cancer. TPA was related to histological stage, T stage, M stage, and TNM stage in patients with IBD and rectal cancer. Serum CA242, CA724, and TPA levels in the survival group were significantly lower than those in the dead group after 3 years (P < 0.001). As for the combined prediction of serum CA242, CA724, and TPA for patients' prognosis, the confidence interval was 0.000-1.000, AUC was 0.875, standard error was 0.093, and sensitivity was 0.750. Conclusion Serum CA242, CA724, and TPA levels are closely related to the clinicopathological features such as location, stage, and metastasis of rectal cancer. The combined detection of serum CA242, CA724, and TPA levels has a significant correlation with the prognosis of patients with rectal cancer, which can be used in monitoring the disease progression.

Tissue polypeptide antigen & interleukin-6: Are their serum levels a predictor for response to chemotherapy in breast cancer?

Objective: To compare the serum level of tissue polypeptide antigen (TPA) and interleukin-6 (IL-6) in women with breast cancer at various stages of the disease and to consider the usefulness of these tumor markers in evaluating the response to chemotherapy. Methods: This case control study included 60 women, from those who were attending the Oncology and Nuclear Hospital in Mosul / Iraq from the period of 1st of March 2012 and 1st of March 2013, complaining of breast cancer of stage 1-4 and receiving chemotherapy after they were operated on. Thirty women age ranged between 29-69 years, were receiving six cycles of chemotherapy after they were operated. This group was compared with the second group of 30 breast cancer women, age ranged between 28-61 years who came for the first time after they were operated on and before receiving chemotherapy. Another 30 apparently healthy, age matched women were included in this study as a healthy control group. The sera obtained from the precipitants used for the estimation of serum TPA and IL-6 level using special commercial kits. Results: The mean serum levels of both TPA and IL-6 were significantly higher in breast cancer patients than healthy control group. The mean serum levels of both TPA and IL-6 in the breast cancer patients who received 6 cycles of chemotherapy were significantly lower than their levels in the breast cancer patients who did not received chemotherapy yet. There was a significant difference among the 4 stages of breast cancer regarding TPA and IL-6 serum levels, the highest value was detected in those with stage IV and the lowest value was detected in those with stage I. The mean serum levels of both TPA and IL-6 were significantly higher in patients with ductal type than those with lobular type in both breast cancer groups. Both TPA and IL-6 are highly sensitive in detecting breast cancer and the combination of the two tumor markers will increase the specificity for detecting breast cancer up to 96.7%. Conclusion: Serum level of TPA and IL-6 discriminates between localized and metastatic breast cancer and their levels are good indicators of disease progression, TPA and IL-6 levels have a good predictive value for response to chemotherapy. The combination of the two tumor markers will increase the specificity for detecting breast cancer up to 96.7%.

Tissue polypeptide antigen as a biological marker of malignant pleural mesothelioma

To evaluate the role of tissue polypeptide antigen (TPA) as a biological marker of malignant pleural mesothelioma (MPM), we used immunohistochemical techniques to detect TPA in tumor cells, and we measured the content of TPA in serum from patients with MPM. In 14 of 16 patients with MPM, TPA was detected in the cytoplasm of tumor cells. Epithelial-type cells from 11 of 12 patients were stained positively (91.7%), and sarcomatous-type cells from 7 of 8 patients were stained positively (87.5%). Serum TPA levels were abnormally high in 7 of 9 patients. Two of three patients with stage-I disease had normal serum TPA levels, and all patients whose disease was at stage II or higher had abnormal serum TPA levels. Serum TPA levels increased as MPM progressed. These results suggest that the serum TPA level can be used as a biological marker of MPM.

Quantitation of tissue polypeptide antigen (TPA) in hepatic and systemic circulation in patients with chronic liver diseases

Abnormal serum tissue polypeptide antigen (TPA) values are commonly found in patients with chronic liver damage and liver cirrhosis even in the absence of malignancies. The aim of this study was to compare serum TPA levels in patients with cirrhosis, to examine correlations between TPA levels and the degree of portal hypertension, and to evaluate TPA concentrations in paired hepatic and peripheral blood samples. A total of 128 patients with chronic liver disease of various severity were studied prospectively. TPA concentrations in hepatic vein and peripheral blood were determined, and Hepatic Vein Pressure Gradient (HVPG) was measured. TPA levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis, and in systemic circulation than in hepatic vein blood. Peripheral but not hepatic TPA levels did correlate with the HVPG. Subjects with clinically significant portal hypertension (HVPG > 10 mmHg) showed significantly higher peripheral TPA levels than those with HVPG < 10 mmHg. Our data suggest that the increased TPA levels observed in cirrhotic patients and the high systemic-to-hepatic blood TPA gradient are probably due to the presence of portal-systemic shunts rather than to hepatic necro-inflammatory activity. In clinical practice, TPA determination could help us to identify and to follow up cirrhotic patients with more severe portal hypertension.

Effect of Opium Smoking on Concentrations of Carcinoembryonic Antigen and Tissue Polypeptide Antigen

Previous studies have related opium and its pyrolysates to the risk of developing certain cancers. The aim of this work was to evaluate the clinical usefulness of determining carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) levels in habitual opium smokers. Serum CEA concentrations were measured in 128 opium smokers and in 44 controls of cigarette only smokers and 47 normal non-smokers by an EIA-based assay. TPA levels were also determined in serum and urine of a subgroup in the study population. The results indicated that serum CEA concentrations are higher in opium smokers than in healthy tobacco smokers (p = 0.004) and non-smokers (p = 0.001). The amount of opium used correlated with the serum CEA level (r = 0.276, p < 0.0001). The mean urine and serum TPA levels of the opium-addicted population were also higher than that of the non-smoking control group, but the differences were not statistically significant. We conclude that opium smoking is associated with elevated serum CEA levels. Therefore, for management of opium users with neoplastic diseases, increased levels of serum CEA should be viewed with caution to avoid misdiagnosis.

Effect of opium smoking on concentrations of carcinoembryonic antigen and tissue polypeptide antigen

Previous studies have related opium and its pyrolysates to the risk of developing certain cancers. The aim of this work was to evaluate the clinical usefulness of determining carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) levels in habitual opium smokers. Serum CEA concentrations were measured in 128 opium smokers and in 44 controls of cigarette only smokers and 47 normal non-smokers by an EIA-based assay. TPA levels were also determined in serum and urine of a subgroup in the study population. The results indicated that serum CEA concentrations are higher in opium smokers than in healthy tobacco smokers (p = 0.004) and non-smokers (p = 0.001). The amount of opium used correlated with the serum CEA level (r = 0.276, p < 0.0001). The mean urine and serum TPA levels of the opium-addicted population were also higher than that of the non-smoking control group, but the differences were not statistically significant. We conclude that opium smoking is associated with elevated serum CEA levels. Therefore, for management of opium users with neoplastic diseases, increased levels of serum CEA should be viewed with caution to avoid misdiagnosis.

Serum biomarkers facilitate the recognition of early- stage cancer and may guide the selection of surgical candidates: A study of carcinoembryonic antigen and tissue polypeptide antigen in patients with operable non–small cell lung cancer

Objectives: Copious literature shows that in lung cancer many serum markers, especially the cytokeratin degradation products, correlate with the extent of disease. In 1995, we suggested the possibility of predicting the resectability of non–small cell lung cancer by measuring the plasma level of the tissue polypeptide antigen, a marker of the cytokeratin family. This study was designed (1) to confirm the earlier data in a new prospective evaluation, (2) to comparatively assess another classic biomarker (ie, the carcinoembryonic antigen), and (3) to incorporate their results into the preoperative evaluation of non–small cell lung cancer. Methods: We analyzed the database of a single institution over a 5-year period (1994-1998) in a community-based hospital and second referral level institution for a province of 500,000 people. The database included 124 consecutive patients (105 men) with pathologically documented lung cancer (50% with adenocarcinoma) accurately staged, clinically judged operable or potentially operable, and eventually operated on. Anthropometric, clinical, and laboratory data (including the carcinoembryonic antigen and tissue polypeptide antigen serum levels) and the results of a complex staging workup were prospectively recorded. Receiver-operating characteristic curves and diagnostic formulas were used for data analysis. Results: Computed tomography of the thorax, upper part of the abdomen, and brain was the most accurate preoperative method to assess tumor resectability (receiver-operating characteristic area: 0.76, 95% confidence intervals: 0.67-0.86, P =.000; accuracy rate: 77%, confidence intervals: 69%-84%). Tissue polypeptide antigen was also predictive for tumor resectability (receiver-operating characteristic area: 0.62, 95% confidence intervals: 0.51-0.73, P =.035; accuracy rate at a threshold level of 110 U/L: 65%, 95% confidence intervals: 56%-73%). Carcinoembryonic antigen was diagnostic only at the extreme values of its distribution (accuracy rate at a level up to 10 ng/mL: 69%, 95% confidence intervals: 60%-77%). The probability of finding resectable disease at the time of the operation increased from 78% (baseline computed tomography–based probability) to 83% when the concentration of tissue polypeptide antigen was lower than 90 U/L and to 85% when the concentration of carcinoembryonic antigen was below 10 ng/mL. The probability of discovering an advanced disease increased from 68% (baseline computed tomography–based probability) to 89% when tissue polypeptide antigen levels were abnormal and to 100% when carcinoembryonic antigen concentrations were higher than 10 ng/mL. Conversely, the predictability of computed tomography was diminished by contrasting biomarker results, requiring further clinical investigations. Conclusions: Computed tomography remains the gold standard for the preoperative evaluation of non–small cell lung cancer, although it may significantly underestimate the real tumor extension. The addition of the easy and inexpensive tissue polypeptide antigen test (with or without carcinoembryonic antigen) is capable of correcting this underestimation and helps to decide whether to completely rely on computed tomography or order additional clinical investigations.J Thorac Cardiovasc Surg 2001;122:891-9

Placental expression of cytokeratin 18 and serum levels of tissue polypeptide antigen in women with pregnancy-induced hypertension.

We hypothesized that placental cytokeratin (CK) 18 expression and serum levels of tissue polypeptide antigen (TPA), a surrogate marker for CK 18, are increased among women with pregnancy-induced hypertension (PIH). Serum levels of TPA were measured in 46 women with PIH and 46 controls, matched for gestational age and parity, using an immunoradiometric assay. Immunohistochemical detection of CK 18 was assessed in placental specimens of 24 women with PIH and 20 controls. Results were correlated to clinical data. Cytokeratin 18 expression was found in the syncytiotrophoblast of 7 of 20 (35%) and 18 of 24 (75%) placental specimens of controls and women with PIH, respectively (p = 0.008). Median serum levels of TPA in controls and women with PIH were 93.0 U/L (range: 12.5-281.6) and 154.2 U/L (range: 37.3-496.6), respectively (p = 0.001). Serum levels of TPA significantly influenced the odds of presenting with PIH, as well as the odds of developing severe disease (p = 0.003, and p = 0.001, respectively). TPA values were significantly higher among women with severe PIH compared with women with mild PIH and controls, independent of gestational age (p = 0.004). Among women with severe PIH, serum TPA was inversely correlated with fetal birth weight (r = -0.3; p = 0.001) Cytokeratin 18 is overexpressed in the syncytiotrophoblast of women with PIH. Serum levels of TPA are elevated among women with PIH and correlate with disease severity and low fetal birth weight.

Placental Expression of Cytokeratin 18 and Serum Levels of Tissue Polypeptide Antigen in Women with Pregnancy-Induced Hypertension

Objective. We hypothesized that placental cytokeratin (CK) 18 expression and serum levels of tissue polypeptide antigen (TPA), a surrogate marker for CK 18, are increased among women with pregnancy-induced hypertension (PIH).Methods. Serum levels of TPA were measured in 46 women with PIH and 46 controls, matched for gestational age and parity, using an immunoradiometric assay. Immunohistochemical detection of CK 18 was assessed in placental specimens of 24 women with PIH and 20 controls. Results were correlated to clinical data.Results. Cytokeratin 18 expression was found in the syncytiotrophoblast of 7 of 20 (35%) and 18 of 24 (75%) placental specimens of controls and women with PIH, respectively (p = 0.008). Median serum levels of TPA in controls and women with PIH were 93.0 U/L (range: 12.5–281.6) and 154.2 U/L (range: 37.3–496.6), respectively (p = 0.001). Serum levels of TPA significantly influenced the odds of presenting with PIH, as well as the odds of developing severe disease (p = 0.003, and p = 0.001, respectively). TPA values were significantly higher among women with severe PIH compared with women with mild PIH and controls, independent of gestational age (p = 0.004). Among women with severe PIH, serum TPA was inversely correlated with fetal birth weight (r = -0.3; p = 0.001).Conclusion. Cytokeratin 18 is overexpressed in the syncytiotrophoblast of women with PIH. Serum levels of TPA are elevated among wornen with PIH and correlate with disease severity and low fetal birth weight.

Elevated tumour markers in patients with Balkan endemic nephropathy.

Balkan nephropathy (BEN) is commonly associated with urothelial cancer. Urothelial cancer is manifested in the advanced stage of disease. The aim of this study was to facilitate early detection of urothelial cancer in BEN patients and their family members living in an endemic region by using tumour markers, carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA), and a putative marker, ferritin. Fifteen BEN patients with normal renal function, 17 with renal failure (BEN-RF), 13 healthy members of their families (HFM), 14 patients with glomerulonephritis (GN) and 12 healthy controls (C) were studied. Serum CEA levels in BEN patients were within normal limits, however, in BEN-RF patients they were significantly increased over HFM (p<0.05). Serum TPA levels in BEN and BEN-RF patients were significantly higher than in the C and HFM groups (p<0.05). Urinary CEA was not significantly different between the groups studied. Urinary TPA levels in HFM (median 125 U/l, BEN (236 U/l) and BEN-RF (275 U/l) were significantly increased over C (30 U/l), however, TPA levels were increased also in GN patients (437 U/l). None of the BEN patients studied developed urothelial cancer during the ten years' follow-up. Markedly elevated urinary TPA-like levels in all patients studied (HFM, BEN, BEN-RF, GN) suggest that urinary TPA may not be a reliable tumour marker. However, the clinical relevance of high TPA levels in BEN patients should be evaluated.

Cytokeratins and proliferation in breast cancer patients

Tissue polypeptide antigen (TPA) was studied in 242 sera and 165 tumor cell cytosols (both evaluations in 67 cases) of breast cancer patients, for which proliferative activity, determined by the TLI technique, was also available. The TPA serum and tumor cell cytosol median values (utilized for measure analysis as cut-off) were 70 U/1 and 377 U/mg cytosol protein, respectively. High serum TPA levels were associated with unfavourable clinicopathological characteristics whereas a higher tumor cell cytosol TPA level was associated with better cytohistological tumor differentiation. Furthermore, no overall correlation was found between serum and tumor cell cytosol TPA levels or between their levels and TLI. When analyzing cases in which serum and tumor cell cytosol TPA values were higher than 100 U/l and 500 U/mg cytosol protein, respectively (n = 28), serum TPA was positively associated with TLI (slope = 12.3 r = 0.55, p < 0.01), while cytosolic TPA resulted negatively associated with TLI (slope = -87.4 r = 0.41, p < 0.01). Finally, a strong inverse relationship between cytosolic and serum TPA (p < 0.0005) became evident. We suggest that TPA could represent a serum marker for tumor cell proliferation in specific patient subgroups with original high serum and/or cytosol TPA expression.

Tissue Polypeptide Antigen Production in a Uterine Carcinosarcoma Cell Line in a Serum-Free Culture

Carcinosarcomas (malignant mixed Müllerian tumors, MMMT) of the female genital tract are uncommon neoplasms, most of which show a highly aggressive behavior. However, the biological characteristics of MMMT, especially the producibility of tumor-related substancesin vitro,have yet to be clarified. Using a serum-free culture model system which was newly established from an FU-MMT-2 cell line originating from an MMMT of the human uterus, the biological and immunocytochemical characteristics of MMMT cells were examinedin vitro.As a control model, the uterine fibroblasts were also cultured in the same conditions. Moreover, several tumor markers were also measured by a radioimmunoassay in the serum of five patients with MMMT. FU-MMT-2 produced and secreted tissue polypeptide antigen (TPA), a tumor marker closely related to the keratin family, under serum-free culture conditions. Moreover, TPA was also immunocytochemically demonstrated in carcinoma cells as well as sarcoma cells in FU-MMT-2. On the other hand, the uterine fibroblasts showed no detectable producibility of the substances examinedin vitro.An elevation of the serum TPA levels was also detected in four of five (80%) patients with MMMT. This is the first serum-free culture study of MMMT, which appears to provide a useful model for further studies of the tumor biology in MMMT of the female genital tract. An evaluation of the serum TPA level thus appears to be useful in determining the optimum management of patients with MMMT. In addition, the demonstration of TPA in sarcoma cells of FU-MMT-2in vitrosupports both the theory of a single cell origin and the current concept of MMMT as a “metaplastic carcinoma,” as substantiated in our previous study.

Tissue polypeptide antigen during parturition and puerperium.

The tumour and cytoskeleton protein tissue polypeptide antigen (TPA) was determined in maternal serum taken during the second stage of labour and on the 4th postpartum day. Pregnant women at term (weeks 38-42) served as a control group. TPA levels of women during parturition (median 169 U/l) were higher than those of the control group (median 108.5 U/l) and those of women on the 4th postpartum day (median 66.5 U/l); p < 0.0001 in each case. The correlation between duration of labour and TPA concentration was positive and significant (rs = 0.3; p = 0.03). A significant negative correlation was found between placental weight and maternal serum TPA levels during parturition (rs = -0.3; p = 0.03). The decline of TPA after delivery indicated a serum half-life for TPA of less than 4 days.

Monitoring lung cancer with tissue polypeptide antigen: an ancillary, profitable serum test to evaluate treatment response and posttreatment disease status

The tissue polypeptide antigen (TPA) is a protein produced and released by proliferating cells that possesses several characteristics for an ideal tumor marker. Our purpose was to define the clinical yield of TPA in the follow-up of patients with lung cancer (LC). Three hundred and forty-one new LC patients underwent an extensive pre-treatment staging evaluation (UICC 1987 classification) and a TPA serum measurement. We restaged them at regular times by: 1, clinical history and physical examination, routine lab tests, chest X-rays, and any other examination as suggested by the prior baseline evaluation, and 2, the serum level of TPA. We evaluated a total of 1513 assays (including 1172 posttreatment measurements). Individual values of TPA correlated significantly with treatment response and disease status. Patients with small-cell lung cancer showed the lowest correlation indexes between clinical parameters and the marker. Each objective response to treatment or disease progression was almost always associated to consistent changes of TPA ( P<0.0001, by the Wilcoxon's test). A 50% reduction under the prior TPA value was 30% sensitive, 90% specific, and 88% accurate in the diagnosis of response to treatment. The same percent reduction was 18% sensitive, 92% specific, and 88% accurate in predicting a future response. A 100% increase over the prior level of TPA permitted to recognize tumor relapses with sensitivity, specificity, and accuracy of 30%, 93%, and 80% (diagnosis of progression), and 18%, 92%, and 78% (prediction of progression). Similar diagnostic yields were observed using progressively increasing or progressively decreasing changes of the marker level. In lung cancer, the diagnosis (and even the anticipation) of disease status is often possible using appropriate threshold value of TPA.

A new human breast cancer cell line, KPL-1 secretes tumour-associated antigens and grows rapidly in female athymic nude mice.

We recently established a new human breast cell line, designated KPL-1, which was derived from the malignant effusion of a patient with breast cancer. This cell line is highly tumorigenic and grows rapidly in female nude mice. Cytogenetic analysis indicated its human origin and revealed a hypertriploid modal number of chromosomes. Electron microscopic examination suggested that the KPL-1 cells are of epithelial origin. Immunohistochemical studies revealed that the cells express cytokeratin, carcinoembryonic antigen and CA 15-3. They also possess a large number of oestrogen receptors but not progesterone receptors. Interestingly, KPL-1 cells seem to grow oestrogen independently in vitro. No amplification of c-erbB-2, c-myc, H-ras and N-ras genes was detected. KPL-1 cells secrete a large amount of tissue polypeptide antigen (TPA). Although the secretion of CA 15-3 seemed to be constant throughout all cell growth phases, TPA secretion increased during the exponential growth phase and decreased during the plateau phase. Serum TPA levels significantly correlated with the volume of KPL-1 tumours transplanted into nude mice. These data suggest that this KPL-1 cell line may be useful for studying oestrogen-independent growth and the kinetics of tumour-associated antigens in vivo as well as in vitro.

Pre-operative serum levels of tissue polypeptide antigen in patients with gastric cancer.

Pre-operative serum tissue polypeptide antigen (TPA) levels were measured in cases of gastric cancer from December 1987 to December 1992. All 351 cases received gastrectomies. The clinicopathological factors were analysed. The significant factors that correlated with the elevation of pre-operative serum TPA levels included tumour size (> 7 cm), Borrmann-type cancers, late stages (III and IV), lymph node metastasis, hepatic metastasis and Ming's expanding type cancers. Multivariate analysis showed that the tumour size (> 7 cm) and the presence of hepatic metastasis are significant factors. To clarify the relationships between gastric cancer per se and the pre-operative serum TPA levels, we selected cases without evidence of metastasis (n = 139). The tumour size was the only significant factor when multivariate analysis was applied. Possibilities of hepatic recurrence were found in cases with high pre-operative serum TPA levels (> 220 U/L), even radical gastrectomies were performed. A high pre-operative serum TPA level did not display a poor survival prognosis, if the radical gastrectomy was possible. We thus concluded that: (i) elevated pre-operative serum levels of TPA are associated with either a large size tumour (> 7 cm) or the presence of hepatic metastasis and the tumour size is the most important factor relating to the serum TPA levels; (ii) high pre-operative serum TPA levels (> 220 U/L) may serve as indicators of later hepatic recurrence; and (iii) elevated serum TPA levels were not indicators of survival prognosis.

The Tissue Polypeptide Antigen Serum Test in the Preoperative Evaluation of Non-Small Cell Lung Cancer: Diagnostic Yield and Comparison With Conventional Staging Methods

Tissue polypeptide antigen (TPA) is a protein produced and released by proliferating cells that has been shown to possess several characteristics for an ideal tumor marker. Our purpose was to determine the yield of TPA in the pretreatment assessment of non-small cell lung cancer (NSCLC), in comparison with a baseline clinical evaluation and multiorgan computed tomography (CT) assumed to be the gold standard for presurgical staging. One hundred four patients with NSCLC underwent thoracotomy, mediastinoscopy, or biopsy of suspected metastatic deposits, in addition to an extensive noninvasive evaluation of their stage of disease. We restaged retrospectively (UICC 1987 classification) these patients, on the basis of the following: (1) clinical history and physical examination, routine laboratory tests, bronchoscopy, chest radiographs, and any other examination as indicated by the prior baseline evaluation (BE stage); (2) the serum level of TPA (TPA stage); (3) the reading of a CT scan of brain, thorax, and abdomen obtained with no limitation to clinical information (CT stage); and (4) pathologic findings (RE stage). The TPA stage was calculated using 20 threshold values ranging from 45 U/L to 450 U/L. On the basis of the RE stage, sensitivity, specificity, accuracy, and predictive capabilities of BE, CT, and TPA were determined for stage I and II (full operability, FO), stage IIIa (possible operability, PO), and stage IIIb and IV (full inoperability, FI). The TPA thresholds were 110 U/L for detecting FO with the highest rate of success, and 160 U/L for detecting FI. Using these thresholds BE, CT, and TPA showed a diagnostic accuracy of, respectively, 75%, 79%, and 68% for FO; 87%, 69%, and 77% for PO; 87%, 77%, and 76% for FI. The accuracy of BE, CT, and TPA for both FO and FI was, respectively, 85%, 69%, and 69%. Of 74 patients classified operable by BE, 6 had a serum concentration of TPA less than 50 U/L and all 6 were confirmed in stage I or II at the subsequent thoracotomy; 15 others, out of 26 patients judged to have inoperable conditions by BE, had a TPA test result above 135 U/L and all 15 were pathologically classified in stage IIIb or IV. Using appropriate threshold values of TPA, it should be possible to predict NSCLC resectability with a diagnostic accuracy similar to that routinely achieved by CT.

Immunoradiometrical Measurement of Tissue Polypeptide Specific Antigen (TPS) in Normal, Healthy, Nonpregnant and Pregnant Japanese Women

Using a monoclonal immunoradiometrical assay, we measured the concentrations of the specific epitope M3 of tissue polypeptide antigen (TPA), namely, tissue polypeptide specific antigen (TPS), in serum and amniotic fluid obtained from normal, healthy, nonpregnant and pregnant Japanese women (NHNJW and NHPJW). The cut-off value of the serum TPS level was set at 130 U/l, based on the mean +2 standard deviations in the NHNJW. The serial measurement of serum TPS levels demonstrated the significant temporal elevation of TPS level near the time of ovulation (+/- 3 days) in the ovulatory women. In the NHPJW, the mean serum TPS level and the positivity rate (> 130 U/l) increased with the advance of gestation, reaching 183.7 U/l and 66.7%, respectively, in the third trimester. Maternal serum levels were much elevated just before (mean: 982.3 U/l) and after (mean: 824.6 U/l) delivery, and were reduced to about one-fourth by 3 days. In addition, markedly high TPS concentrations were found in the retroplacental blood (one case: 9,076 U/l) and the amniotic fluid (mean: 11,650 U/l). The serum TPS level correlated well (r = 0.871) with the serum TPA level in the TPS range of 2-2,000 U/l, while a poor correlation (r = 0.273) was found in the TPS range of 2-500 U/l. The present study thus obtained fundamental data on TPS in Japanese women. The fluctuation and change of serum TPS levels during the menstrual cycle and in pregnancy should be taken into consideration when we apply TPS as a tumor marker for women.

Evaluation of tissue polypeptide antigen serum levels for monitoring disease activity during chemotherapy in patients with transitional carcinoma of the urinary tract

In 28 patients with transitional carcinoma of the urinary tract, all treated with chemotherapy, serial measurements of serum tissue polypeptide antigen (TPA) were performed and correlated to clinical evaluations of response. At the start of chemotherapy elevated levels of TPA were found in 4 out of 14 patients with T2-4NO-2MO tumours and in 7 out of 14 patients with distant metastases. In most patients with elevated TPA levels who responded to chemotherapy, TPA levels rapidly returned to normal. False positive elevations of TPA were observed in 2 patients. It is concluded that serial measurement of TPA for monitoring disease activity has limited value because of the low sensitivity of TPA, especially for patients with early-stage cancer, and because of the occurrence of false positive results.

A clinical and laboratory evaluation of the behavior of tissue polypeptide antigen in liver cirrhosis.

Serum tissue polypeptide antigen (TPA) was determined in 86 cirrhotic patients who underwent a thorough clinical and laboratory evaluation. Increased serum TPA levels were found in 87.2% of the patients (81% of Child's A, 81.3% of Child's B and 97% of Child's C) with very high levels in some cases. There were significant correlations between TPA and several clinical and biochemical tests, especially AST (r = 0.678, p < 0.000001), and this enzyme was the best predictor of TPA levels. Patients with abnormal AST had also significantly higher serum levels of TPA than those with normal AST in each of the Child's class (p < 0.01 for each). TPA values were found to be more frequently abnormal than AST ones in cirrhotics (p = 0.009) and could be used as indirect markers of activity in these patients. The underlying mechanism involved in the increase in TPA in cirrhosis was probably related to the cytolytic/regenerative activity of the liver. TPA cannot be used as a tumor marker in these patients.