Serum TPS Research Articles

Elevated serum levels of TPS and CYFRA 21-1 predict poor prognosis in advanced non-small-cell lung cancer patients treated with gefitinib

Serum concentrations of tissue polypeptide-specific antigen (TPS) and Cytokeratin-19-Fragments (CYFRA 21-1) before operation or chemotherapy have been proved to be a useful prognostic tool for patients with NSCLC, but the related data for advanced NSCLC patients treated with gefitinib are limited. We retrospectively reviewed 122 advanced NSCLC patients treated with gefitinib between April 2002 and August 2007. Multiple clinical factors including pretreatment serum levels of TPS and CYFRA 21-1, age, gender, performance status (PS), smoking history, stage, histology, the number of prior chemotherapy and the patients' clinical outcomes were analyzed. Patients without elevated serum TPS levels had a more RR (36.8%) than those with elevated serum TPS levels (18.5%) (P = 0.023), nevertheless, a similar result was not seen in patients with normal CYFRA 21-1 levels. For patients with normal vs. high TPS levels, the median survival times (MSTs) were 15.9 vs. 7.3 months (P = 0.001). For patients with normal vs. high CYFRA 21-1, the MSTs were 15.4 vs. 7.5 months (P = 0.003). Moreover, for patients with both elevated, vs. one elevated and both normal TPS and CYFRA 21-1 levels, the MSTs were 5.4 vs. 11.4 months (P = 0.001), and 16.5 months (P < 0.001), respectively. In multivariate analysis, TPS (P = 0.001) and CYFRA 21-1 (P = 0.005) alone or combination (P < 0.001) remained significant correlation to survival. In NSCLC patients with gefitinib therapy, pretreatment serum levels of TPS and CYFRA 21-1 alone or combined might be independent prognostic factors, and the pretreatment serum TPS level may predict the tumor response.

Serum Levels of Keratin-18 Fragments [Tissue Polypeptide-Specific Antigen (TPS)] Are Correlated with Hepatocyte Apoptosis in Alcoholic Hepatitis

Apoptosis is a major feature in alcoholic hepatitis. During apoptosis, the M30 neoepitope becomes exposed after keratin-18 cleavage. The tissue polypeptide-specific antigen (TPS) is a keratin-18 fragment that is routinely used as a tumor marker. Serum TPS levels are increased in patients with alcoholic hepatitis. The aim of this study was to investigate the possible relationship of TPS levels with hepatocyte apoptosis in alcoholic hepatitis. Thirty-one patients with alcoholic hepatitis and 22 with fatty liver were included. Hepatocyte apoptosis was evaluated by M30 immunostaining. Serum TPS levels were measured by a commercial immunoassay. The apoptotic score was higher in patients with alcoholic hepatitis than in patients with fatty liver. There was a significant correlation between the apoptotic score and TPS levels. The correlation of the apoptotic score with TPS levels was stronger than with standard liver tests. Serum TPS may be a marker of apoptosis in alcoholic hepatitis.

Using the Direct-Injection Model of Early Uveal Melanoma Hepatic Metastasis to Identify TPS as a Potentially Useful Serum Biomarker

To develop a method to screen for serum biomarkers of early hepatic metastasis from uveal melanoma. Cytokeratin 18 (TPS) was identified from gene expression profiles as protein generated by highly invasive uveal melanoma cells. Sera were collected from two groups of 15 SCID mice 2 weeks after injection of either tissue culture medium or MUM2B human metastatic uveal melanoma cells into the mouse liver. Serum TPS levels were assayed in 53 healthy human controls, 64 uveal melanoma patients who were disease free for at least 10 years, and 37 patients with metastatic uveal melanoma. After 2 weeks, small hepatic nodules (0.1-2.8 mm; mean, 0.80 mm) developed in 11 of 15 mice injected with MUM2B cells. Serum TPS levels in media-injected mice (84.7 U/L) were substantially lower than levels in MUM2B-injected mice (601 mug/L). TPS levels were significantly higher (P < 0.0001) in patients with metastatic uveal melanoma (139.63 +/- 22.20) than in healthy controls (54.23 +/- 0.01) or in patients free of disease (69.29 +/- 9.76). Significant differences were found between TPS levels before and after the development of hepatic metastases (P < 0.01), and serum TPS levels became elevated in four patients at least 6 months before the detection of hepatic metastases by abdominal ultrasonography. The direct-injection model of uveal melanoma in the mouse liver may be used to screen for potential serum biomarkers of metastatic uveal melanoma.

Serum levels of cytokeratin‐18 (tissue polypeptide‐specific antigen) in liver diseases

The tissue polypeptide-specific antigen (TPS, cytokeratin-18, a normal constituent of the hepatocyte cytoskeleton) is a standard tumour marker. This study aimed to evaluate serum TPS levels in patients with liver disease. Serum TPS was measured with a commercial immunoassay in 884 individuals (753 outpatients from a liver disease clinic, 131 patients admitted to the hospital with acute liver disease). Abnormally high (> 80 U/l) TPS levels were found in 57.7% (95% CI 54.0-61.3%) of outpatients with liver disease. Elevated TPS levels were observed for all liver diseases, including fatty liver, alcoholic disease, chronic viral hepatitis, autoimmune hepatitis, cholestasis, transplantation, and hepatocarcinoma. TPS levels correlated with liver markers, particularly serum AST. In addition, TPS levels correlated with Knodell's score in patients with chronic hepatitis. TPS was increased in one-third of patients with normal liver enzyme values. Serum TPS levels decreased after specific therapy in patients with hepatitis C and autoimmune hepatitis. Abnormally high TPS levels were found in the vast majority of patients admitted to the hospital, with markedly high (> 800 U/l) values being observed in 47.5% (95% CI 36.1-55.7%) of patients with alcoholic liver disease and in 80.8% (95% CI 60.0-92.7%) of patients with acute hepatitis. Serum TPS (cytokeratin-18) is elevated in patients with non-malignant liver diseases, particularly in those with prominent cytolysis. Further studies are needed to evaluate the use of TPS as a marker of liver disease.

Serum cytokeratins in alcoholic liver disease: contrasting levels of cytokeratin-18 and cytokeratin-19

Serum cytokeratin (CK) levels are widely used as tumor markers. Serum levels of CK-18, a tumor marker also known as tissue polypeptide specific antigen (TPS), are increased in patients with alcoholic liver disease. Cytokeratin-18 is the main component of Mallory bodies, a hallmark of alcoholic hepatitis, which may also contain CK-19. Serum levels of CK-18 and CK-19, a tumor marker also known as CYtokeratin FRAgment 21-1 (CYFRA 21-1) were investigated in (a) heavy drinkers with alcoholic liver disease ( n = 15), (b) patients with malignancy ( n = 22), and (c) healthy controls ( n = 10). Serum levels of CYFRA 21-1 (CK-19) were markedly increased in patients with malignancy, but were similar in heavy drinkers and healthy controls. In contrast, serum levels of TPS (CK-18) in heavy drinkers were higher than those of healthy controls, and even tended to be higher than those of patients with malignancy. Both CK-19 and CK-18 levels were higher in cases of alcoholic hepatitis than in cases of fatty liver. Correlation with hepatocyte CK inclusions was stronger for serum TPS (CK-18) than for CYFRA 21-1 (CK-19). In conclusion, serum CYFRA 21-1 (CK-19) and TPS (CK-18) show a different pattern of increase that could reflect the composition of the altered hepatocyte CK network in alcoholic liver disease. Their usefulness as tumor markers, particularly that of serum TPS (CK-18), may be limited in patients with alcoholic liver disease.

Correlation between pre-therapeutic TPS and VEGF concentrations, in the serum of patients with cancer of the uterine cervix, and early effects of therapy

Summary Aim To assess the relationship between pre-therapeutic serum TPS and VEGF levels and the results of treatment as measured immediately after completion of therapy. Materials/Methods The study included 146 women treated for cancer of the uterine cervix. Of these, 37 women were in stage I, 43 in stage II, 59 in stage III and 7 in stage IV of disease progression according to the FIGO classification. The ages of the patients ranged from 31 to 80 years. The dominant cancer observed was squamous cell carcinoma which accounted for more than 97% of cases. Samples were taken before commencement of treatment. Patients were treated by a combination of methods including radiochemotherapy, radical radiotherapy and palliative radiotherapy. The effects of therapy were graded after completion of irradiation according to generally accepted criteria. For tested criteria, ROC curves were drawn, determining cut-off points of 58 U/l for TPS and 500 pg/l for VEGF. For statistical calculations the U Mann-Whitney test was used. Results The level of VEGF expression varied between groups of patients in certain stages of disease progression (stages 1 & 2 and stages 2 & 3). Statistically significant differences were found between group PR in stage 2 and a control group of healthy women. Entry levels of TPS rose with tumor advancement (in stages 2, 3 & 4) and were higher than in a group of healthy women. Detected differences were statistically significant. Conclusions Only pre-therapeutic TPS levels show definite differences between degrees of clinical advancement and also with early therapeutic effects. Comparatively higher levels of serum TPS were found in patients with the worst prognosis prior to treatment (group P) than in the control group. This difference is statistically significant. Pre-therapeutic VEGF levels showed statistically significant differences between early (I, II) and advanced (III) clinical stages of the tumor as well as some effects of therapy assessed immediately after completion of treatment (PR vs S).

Indicative markers of cell proliferation and apoptosis during the perinatal period.

Tissue polypeptide-specific antigen (TPS), an indicative marker of cell proliferation and soluble Fas (sFas), an antiapoptotic molecule were determined in neonatal serum (day 1-N1 and day 4-N4 of life), compared with maternal serum (MS) and umbilical cord serum (UC) to study changes of these markers during the perinatal period. Serum TPS and sFas concentrations were measured in 33 healthy, termed neonates, their mothers and 25 healthy nonpregnant controls (CS), age-matched to the mothers. TPS serum concentrations were significantly elevated in N1 and N4 as compared to CS (p < 0.0001 and p < 0.0003), increasing significantly from UC to N1 (p < 0.0001) and decreasing thereafter in N4 (p < 0.0002). MS serum concentrations, being significantly higher than CS (p < 0.0001), UC (p < 0.0001) and N4 (p < 0.003), but lower than N1 (p < 0.02) were strongly depended on the mode of delivery (p < 0.001). Serum concentrations of sFas, being lower in UC than in MS or CS (p < 0.0001), increased significantly in N4 samples (p < 0.01). A strong correlation was found between sFas serum concentrations in N1 and N4 (r = 0.65; p < 0.001). Our results demonstrate significant perinatal changes in TPS and sFas serum concentrations, possibly indicating gradual decrease of proliferation and apoptosis in early postnatal life.

Role of Tissue Polypeptide Specific Antigen in the Detection of Prostate Cancer

Objective: The aim of the present study was to evaluate the role of tissue polypeptide specific antigen (TPS) in the diagnosis of different stages of prostatic cancer (CaP) and to compare the diagnostic efficacy of serum TPS in respect to total prostate-specific antigen (tPSA) and free/total (f/t) PSA ratio. Patients and Methods: Patients with BPH (n = 58), localized CaP (n = 37) and metastatic CaP (n = 16) were compared by measuring serum TPS, tPSA and f/t PSA ratio. Results: Serum TPS was significantly increased only in patients with metastatic CaP (p < 0.05) and TPS levels was not significantly different between patients with BPH and localized CaP. Both f/tPSA and tPSA showed better sensitivity, specificity and receiver operating curve analysis in the differential diagnosis of BPH and localized CaP. Conclusion: In conclusion, serum TPS measurement was found to be significantly increased in metastatic prostatic carcinoma cases but was not useful in the early detection of prostatic carcinoma. Although there are several studies demonstrating the usefulness of TPS in the differential diagnosis of prostate cancer, there is increasing evidence for the use of this molecule in the late period of the disease or as an adjunct to other molecules in the detection of recurrences.

Serum tissue polypeptide specific antigen as a noninvasive prognostic indicator for early recurrence of hepatocellular carcinoma after curative resection.

Serum tissue polypeptide specific antigen (TPS) is a useful cell proliferation marker in diagnosing and monitoring patients with a variety of malignancies. The objective of this study was to determine the usefulness of serum TPS as a noninvasive prognostic factor for early recurrence of hepatocellular carcinoma (HCC) after patients undergo curative resection. Serum TPS levels were measured by monoclonal TPS immunoradiometric assay in 54 patients shortly before they underwent curative resection for HCC. The recurrence time was correlated with the TPS level and with other prognostic factors using the log-rank test in univariate analysis and a Cox regression in multivariate analysis. Receiver operating characteristic analysis was performed to examine the power of the various prognostic factors to distinguish between patients with recurrent tumors and patients who were disease free. Patients who had higher levels of TPS (>or= 150 U/L) had earlier recurrences compared with patients who had lower levels of TPS (< 150 U/L; P = 0.016) in univariate analysis. Tumor size, the number of tumors, portal vein invasion, and the resection margins also were associated significantly with the time to tumor recurrence (P = 0.015, P = 0.004, P = 0.003, and P = 0.003, respectively). Serum alpha-fetoprotein was not a significant risk factor for tumor recurrence. In multivariate analysis, the TPS level, tumor size, and resection margins were independent prognostic factors (P = 0.025, P = 0.018, and P = 0.016, respectively). The inclusion of TPS in addition to tumor size and resection margins increased the rate of corrective prediction from 0.72 to 0.80. The current study demonstrated that the preoperative serum TPS level was a significant factor in predicting early recurrence of HCC after curative resection. Patients with high serum TPS levels warrant more aggressive treatment and close follow-up after they undergo tumor resection.

Telomerase activity, and tissue polypeptide specific antigen (TPS) in Egyptian breast cancer patients

Objectives: Breast cancer is the most common malignancy among Egyptian women. The aim of this study is to evaluate the role of both telomerase and TPS estimation in assessment of breast cancer. Methods: The study included 40 patients with breast cancer, and 20 patients with benign breast diseases. Telomerase activity in breast tissues was assessed using TRAP assay. TPS was measured in sera of the patients by ELISA. Results: Telomerase positivity was 15% in benign group vs. 60% in malignant group ( p = 0.0009). It was significantly correlated to stage, and lymph node status ( p < 0.02). Telomerase positivity showed significant correlation to tumor recurrence ( p = 0.0076) in a follow-up period of 36 months. Mean rank of TPS was significantly higher in malignant than benign groups ( p < 0.001), and in telomerase positive than telomerase negative patients ( p < 0.001). In malignant group, mean rank of TPS was significantly higher in late stages ( p < 0.002), in higher grade ( p < 0.05), in larger tumor size ( p < 0.01), and in lymph node positive patients ( p < 0.001). ROC curve was utilized to choose the best cutoff for serum TPS (88 U/L). At this cutoff, the sensitivity was 95%, and the specificity was 75%. At a higher cutoff (109 U/L), TPS positivity was significantly correlated to stage, grade, lymph node status, and telomerase positivity ( p < 0.05). Conclusion: Telomerase positivity and serum TPS might be used as additional markers for assessment of breast cancer.

Usefulness of Tissue Polypeptide-Specific Antigen in the Management of Ovarian Cysts

The aim of this study was to investigate whether the tissue polypeptide-specific antigen (TPS) levels in cystic fluid, peritoneal fluid, and blood could be used as a marker for the management of ovarian mass. Forty-one patients participated in the study with preoperative diagnosis of an ovarian mass. The patients were divided into two groups according to the results of the histopathologic examination. Group 1 included patients with a benign ovarian mass, and Group 2 included patients with ovarian cancer. Blood samples were taken just before surgery, and cystic fluid and peritoneal fluid were taken at the time of the operation. Comparison of the results between the two groups was performed with the Wilcoxon signed-rank test. There was a statistically significant difference between the TPS serum values in Group 1 compared with Group 2 (p = 0.004). Also, the mean levels of TPS in the serum of patients in Group 2 were significantly higher compared with the cutoff value provided by the manufacturer (80 U/L) and compared with the mean levels of TPS of patients in Group 1. Also, there was a statistically significant difference between the TPS values of the cystic fluid between the two groups (p < 0.05). This study suggests that serum TPS values can be used as a sensitive marker in differentiating malignant from benign ovarian cysts.

Clinicopathologic Correlation of Serum Tissue Polypeptide Specific Antigen in Hepatocellular Carcinoma

Objective: Recently, tissue polypeptide specific antigen (TPS) has been introduced as a cell proliferation marker. Little is known about its clinical significance in hepatocellular carcinoma (HCC). This study aimed to clarify serum TPS levels and tumor invasiveness of HCC. Methods: Serum TPS levels were determined with a monoclonal TPS IRMA assay in 69 patients with HCC. A correlation between serum TPS levels and clinical, biochemical, and pathological features was sought and compared with that of α-fetoprotein (AFP). In 57 healthy subjects, 56 patients with biopsy-proven chronic hepatitis and in 49 patients with liver cirrhosis, serum TPS levels were assayed and compared. Results: Serum TPS levels were significantly correlated with glutamic oxalacetic transaminase (p < 0.0001), glutamic pyruvic transaminase (p < 0.001), and lactate dehydrogenase (p = 0.027). There tended to be a positive relationship between serum TPS levels and tumor size, histological differentiation, capsular invasion, portal invasion, and clinical staging, although it did not reach statistical significance. A significant correlation, however, was observed between AFP and tumor size (p = 0.01), number (p = 0.042), histological grading (p = 0.028), portal invasion (p = 0.009), and clinical staging (p = 0.03). Patients with HCC had significantly higher TPS than healthy subjects (p < 0.001). However, there was substantial overlap between patients with HCC, chronic hepatitis, and liver cirrhosis. Conclusions: Our data suggest that serum TPS is not significantly related to tumor invasiveness in patients with HCC. Serum TPS levels are affected by the proliferative activity of the underlying chronic liver disease, which is frequently associated with HCC in Chinese patients. As a cell proliferation marker, serum TPS should be interpreted cautiously in the presence of chronic liver disease.

Prognostic Significance of CA 125 and TPS Levels after 3 Chemotherapy Courses in Ovarian Cancer Patients

Objective. To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients.Methods. We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients. The prognostic significance of CA 125 and TPS levels above the discrimination value (25 kU/L and 100 U/L, respectively) was examined by univariate and multivariate analyses.Results. Of the 213 cases included, 64 patients were staged as FIGO I + II and 149 patients were staged as FIGO III + IV. Tumor marker levels in stage I + II were not correlated with survival. However, stage III and IV patients with elevated levels of CA 125 or TPS after three chemotherapy courses had a worse 2-year OS (69% vs 26%, P < 0.0001 and 57% vs 20%, P < 0.0001, respectively) than patients with normal levels of the markers. In univariate analysis the result of operation (staging laparatomy and partial debulking) and advanced FIGO stage (IV) were also adverse prognostic factors. Independent factors predictive of low 2-year OS by multivariate analysis were staging laparotomy, TPS elevated, and CA 125 elevated. The only factors predictive of low 1-year OS were TPS elevated and staging laparotomy.Conclusions. Ovarian cancer patients with elevated CA 125 levels after three chemotherapy courses have a poor prognosis. However, the prognostic accuracy can be significantly increased by the parallel determination of serum TPS.

Increased Serum Tissue Polypeptide Specific Antigen (TPS) in Alcoholics: A Possible Marker of Alcoholic Hepatitis

Serum tissue polypeptide specific antigen (TPS) is widely used as a tumor proliferation marker. There is some evidence of an increase in serum TPS in benign liver diseases. The aim of the study was to evaluate serum TPS levels in alcoholics. Seventy-seven alcoholics (64 men and 13 women) admitted to the hospital with ethanol withdrawal syndrome entered the study. Twenty-three patients were biopsied (12 of them had alcoholic hepatitis and 11 steatosis or fibrosteatosis). Serum TPS was determined by enzyme immunoassay in all cases. Results were compared with those of 24 healthy controls. Serum TPS levels were significantly increased in alcoholic patients compared with controls (median 365 units/liter and range 41-6400 units/liter versus median 79 units/liter and range 19-235 units/ liter, respectively, p < 0.0001). Seventeen alcoholics (22%) had a TPS value 10 times higher than the upper normal threshold level (> or = 1000 units/liter). Among alcoholics, serum TPS levels were higher in patients with alcoholic hepatitis than in those with steatosis or fibrosteatosis (median 1486 units/liter and range 176-5023 units/liter versus median 106 units/liter and range 41-221 units/liter, respectively, p = 0.0001), offering a better discriminant value for the diagnosis of alcoholic hepatitis than usual liver function parameters. Serum TPS values showed significant correlation with liver cell necrosis and Mallory's hyaline degeneration. TPS values decreased after alcohol abstinence during hospital admission. Serum TPS is frequently increased in alcoholics and may be a marker of alcoholic hepatitis. Specificity of this molecule as a tumor marker is limited in alcoholics.

Clinical evaluation of serum tissue polypeptide specific antigen in patients with thyroid carcinoma.

There is no specific marker for diagnosis of thyroid cancer with the exception of carcinoembryonic antigen (CEA) and calcitonin for medullary thyroid carcinoma. Tissue polypeptide antigen (TPA) is known to be a diagnostic marker of malignant neoplasms. TPA is also one of the tumor markers for thyroid cancer, but serum TPA shows poor specificity because of polyclonal antibody. Tissue polypeptide specific antigen (TPS) is detected by the monoclonal antibody M3, directed at 1 of the 35 epitopes in TPA. TPS appears in proliferative tumor cells. We examined 72 patients (32 thyroid carcinoma, 20 thyroid adenoma, 5 adenomatous goiter, and 15 diffuse goiter) and 24 healthy volunteers for serum TPS, TPA, and thyroglobulin (Tg). The TPS in thyroid carcinoma was significantly higher than in healthy controls and thyroid adenoma (p < 0.05). The mean value of TPS for all diseases except thyroid carcinoma was below the cutoff value (95 U/L). The TPS sensitivity, specificity, and accuracy for thyroid carcinoma was 37.5%, 100%, and 64.9% respectively. There were no significant differences in mean values of serum Tg and TPA between thyroid carcinomas and adenomas. Positive rates of tissue TPS expression in thyroid carcinomas and adenomas were 87.5% (7/8) and 14.3% (1/7), respectively. The positive rates for serum TPS and immunoreactive TPS in the tissue correlated significantly (p < 0.0001). It is concluded that TPS is a useful marker for diagnosis of thyroid carcinoma.

Neuron-specific enolase, thymidine kinase, and tissue polypeptide-specific antigen in diagnosis and response to chemotherapy of small-cell lung cancer.

The clinical usefulness of neuron-specific enolase (NSE), thymidine kinase (TK), and tissue polypeptide-specific antigen (TPS) was investigated in 41 patients (53-80 years old) with recently discovered small-cell lung cancer (SCLC). Eleven patients exhibited limited disease (LD) and 30 extensive disease (ED). Serum samples for NSE, TPS (immunoradiometric assay), and TK (radioenzymatic assay) evaluations were drawn from all patients at the time of diagnosis and before each cycle of chemotherapy in the treated patients. Therapy consisted of i.v. carboplatin 300 mg/m2 on the first day and i.v. etoposide 120 mg/m2 from the first to the third day every 3 weeks. Nine patients refused or were not eligible for chemotherapy. Five patients received only one course and showed no response (NR); 9 patients received two courses; 18 patients received three or more courses. In the last group, complete remission (CR) was obtained in 9 cases, partial remission (PR) in 18 cases. The tumor markers studied did not show any significant difference in distinguishing LD from ED. NSE and TPS were significantly more often abnormal than TK, either at the time of diagnosis (p < 0.05) or in PR or NR patients (p < 0.05). In relation to chemotherapy response, NSE and TPS serum patterns were shown to be more reliable than TK in PR (p < 0.05) and NR patients (computed error between 10% and 15%). No significant difference was observed between serum NSE and TPS patterns. Serum NSE and TPS seem to be more useful in the diagnosis and follow-up of SCLC patients undergoing chemotherapy. Further trials are necessary to ascertain whether the associated assessment of NSE and TPS can add useful information to that provided by the assessment of NSE alone.

The value of serum tissue polypeptide specific antigen in the diagnosis of hepatocellular carcinoma

Tissue polypeptide specific antigen (TPS) recently was introduced as an indicator of cell proliferation in various tumors. The authors investigated the value of serum TPS as a complement to alpha-fetoprotein (AFP) in the detection of hepatocellular carcinoma (HCC) in Chinese patients. Serum TPS and AFP levels were measured by monoclonal immunoradiometric assay in 85 subjects (52 males and 33 females): 26 with HCC, 30 with chronic hepatitis (CH), and 29 healthy controls. Patients with HCC had significantly higher TPS levels compared with healthy controls (P < 0.05). However, the difference between the HCC and CH groups was not significant (P = 0.18). The sensitivity and specificity of TPS were 73.1% and 71.2%, respectively, with a cutoff value of 164 U/L for HCC diagnosis. TPS had lower discriminatory power compared with AFP (72.1% vs. 79.2%). In addition, TPS had a much lower specificity compared with AFP (89.1%). Combining the cutoff values for serum TPS and AFP levels in a pessimistic prognostic rule increased the sensitivity by 11.6% from 69.2% using serum AFP levels alone, but reduced the diagnostic power by 3.7% to 75.5% due to an 18.9% decrease in specificity to 70.2%. Using TPS alone offers no advantage over AFP for the diagnosis of HCC in Chinese patients. In conjunction with AFP, TPS reduced the false-negative rate. However, the clinical utility of the combined prognostic rule is limited due to the poor discriminatory power of TPS for HCC and CH. Therefore, the use of serum TPS levels in the detection of HCC is not recommended.

Markov model and markers of small cell lung cancer: assessing the influence of reversible serum NSE, CYFRA 21-1 and TPS levels on prognosis.

High serum NSE and advanced tumour stage are well-known negative prognostic determinants of small cell lung cancer (SCLC) when observed at presentation. However, such variables are reversible disease indicators as they can change during the course of therapy. The relationship between risk of death and marker level and disease state during treatment of SCLC chemotherapy is not known. A total of 52 patients with SCLC were followed during cisplatin-based chemotherapy (the median number of tumour status and marker level assessments was 4). The time-homogeneous Markov model was used in order to analyse separately the prognostic significance of change in the state of the serum marker level (NSE, CYFRA 21-1, TPS) or the change in tumour status. In this model, transition rate intensities were analysed according to three different states: alive with low marker level (state 0), alive with high marker level (state 1) and dead (absorbing state). The model analysing NSE levels showed that the mean time to move out of state ‘high marker level’ was short (123 days). There was a 44% probability of the opposite reversible state ‘low marker level’ being reached, which demonstrated the reversible property of the state ‘high marker level’. The relative risk of death from this state ‘high marker level’ was about 2.24 times greater in comparison with that of state 0 ‘low marker level’ (Wald's test; P < 0.01). For patients in state ‘high marker level’ at time of sampling, the probability of death increased dramatically, a transition explaining the rapid decrease in the probability of remaining stationary at this state. However, a non-nil probability to change from state 1 ‘high marker level’ to the opposite transient level, state 0 ‘low marker level’, was observed suggesting that, however infrequently, patients in state 1 ‘high marker level’ might still return to state 0 ‘low marker level’. Almost similar conclusions can be drawn regarding the three-state model constructed using the tumour response status. For the two cytokeratin markers, the Markov model suggests the lack of a true reversible property of these variables as there was only a very weak probability of a patient returning to state ‘low marker level’ once having entered state ‘high marker level’. In conclusion, The Markov model suggests that the observation of an increase in serum NSE level or a lack of response of the disease at any time during follow-up (according to the homogeneous assumption) was strongly associated with a worse prognosis but that the reversion to a low mortality risk state remains possible. © 1999 Cancer Research Campaign

Diagnostic value of tissue polypeptide-specific antigen (TPS) in neuroblastoma and Wilms' tumour.

Although tissue polypeptide-specific antigen (TPS) has been described as a potentially useful serum marker of tumour activity in adult epithelial tumours, few data are available for childhood malignancies. Neuroblastomas and Wilms' tumours are the commonest types of solid malignancies found in the retroperitoneum of children. At this time, a widely used marker for Wilms' tumour is not available. Using an enzyme-linked immunosorbent assay (ELISA) kit, serum TPS levels in 23 children with neuroblastomas, nine with Wilms' tumours and 22 with benign tumours were evaluated to test the usefulness of the marker in identifying malignancies. Compared with healthy children (n = 110), the preoperative least-square means (LSM) of serum TPS were considerably elevated in both neuroblastoma (LSM = 209 U l(-1)) and Wilms' tumour (LSM = 235 U l(-1)), whereas values in benign tumours were only slightly elevated. Although the Wilms' tumours were associated with higher preoperative serum TPS levels, there was no statistically significant difference compared with neuroblastomas. Receiver operating characteristic analysis (ROC curves) showed a high sensitivity and specificity for both malignancies. Successful treatment resulted in decrease in TPS serum values. Serum TPS measurements in children presenting with abdominal masses can help in diagnosing the two commonest extracranial solid malignancies of childhood. Furthermore, TPS could acquire a pivotal role in monitoring therapy.

Predictive factors of tumor response and prognostic factors of survival during lung cancer chemotherapy.

The aim of this study was (i) to determine predictive factors of a complete response to chemotherapy in small cell lung cancer (SCLC) and predictive factors of an objective response in non-small cell lung cancer (NSCLC) and (ii) to determine whether prognostic factors are different with regard to treatment response and survival. Ninety-nine patients with SCLC and two hundred and two patients with NSCLC received chemotherapy. The following variables were recorded prior to treatment: tumor, node, metastasis status, performance status, body weight loss, blood leukocyte count, serum sodium, serum albumin, lactate dehydrogenase (LDH), alkaline phosphatase, serum NSE, serum TPS, and serum CYFRA 21-1. Tumor response was analyzed at the 10th week. Analysis of survival were done using the landmark method. Hazard ratios of the significant prognostic variables of survival were calculated using the Cox's model. Odds ratios of the significant predicting factors of response were calculated by stepwise logistic regression. In SCLC, the significant determinants of poor survival were: lack of complete response (HR: 2.04), weight loss (HR: 1.76), high serum LDH level (HR: 1.64), and high serum TPS level (HR: 2.47). A high serum TPS level was the only factor among those studied able to predict lack of achievement of complete response (OR: 0.39). In NSCLC, significant determinants of poor survival were: no objective response (HR: 2.28), poor performance status (HR: 2.52), presence of metastases (HR: 1.51), and high serum CYFRA 21-1 level (HR: 1.84). On the other hand, a high serum TPS level (OR: 0.50), the presence of metastases (OR: 0.45), and a leukocyte blood count over 10,000/microl (OR: 0.43) were independent determinants for a patient not to achieve an objective response. We concluded that the predictive factors of complete response in SCLC remain to be defined. On the other hand, in NSCLC three variables contribute to the prediction of an objective response. Finally, determinants of survival differ from predictive factors of response.