Tissue polypeptide-specific antigen (TPS) in monitoring palliative treatment response of patients with gastrointestinal tumours.

The new proliferation marker, tissue polypeptide-specific antigen (TPS), representing the specific epitope M3 of tissue polypeptide antigen, and three conventional biochemical markers, CEA, CA 19-9 and CA-195, were analysed in 69 patients with advanced gastrointestinal tumours. The aim of our study was to assess the clinical relevance of these markers and to determine whether their use in monitoring the course of the disease can reduce the need for serial imaging procedures. At baseline, pathologically elevated TPS levels occurred in 90% of patients. CEA was elevated in 73%, CA 19-9 in 59% and CA-195 in 68%. With a detection rate of > 90% in both advanced colorectal (n = 37) and pancreatic cancer (n = 20), and of 75% in gastric cancer (n = 12), TPS was the most sensitive marker in all three tumour types included in this analysis. Serial evaluations of TPS and other biochemical markers were available in 39 patients undergoing palliative systemic chemotherapy. Treatment with a fluorouracil-based regimen resulted in a partial response in 5/27 patients with colorectal cancer, whereas 2/12 patients with pancreatic cancer responded to therapy with a high-dose epirubicin combination regimen. All other patients had disease stabilisation or suffered from progressive disease. When compared with the results of serial CT scanning, the TPS correlated best with the course of the disease, the positive predictive value being 75% for a partial response, 96% for stable disease and partial response combined and 100% for progressive disease. The corresponding values for CEA were 50%, 81% and 62% and were similar to those for CA 19-9 and CA-195. In summary, TPS seems to represent a sensitive, clinically relevant and specific marker of proliferative activity in gastrointestinal cancer. According to our preliminary results in colorectal and pancreatic cancer, TPS may be considered as the primary means of monitoring treatment, and imaging reduced to confirm the response.     

Prognostic value of proliferating cell nuclear antigen in Wilms' tumour in children.

AIMS: To evaluate the prognostic value of index Proliferating Cell Nuclear Antigen (PCNA) in Wilms' tumour in children. METHODS: The study comprised 64 children aged from 2 days to 13 years treated according to the SIOP (Society International of Oncology Paediatric) and accepted by the PPGGL (Polish Paediatric Group for the Treatment of Solid Tumours). The studies were conducted on tumour tissue removed during surgery, fixed in formalin and embedded in paraffin blocks. Sections (4 microns) were evaluated by immunohistochemistry, using the peroxidase method to determine the expression of PCNA in Wilms' tumour cells by primary monoclonal antibody NCL-PCNA from Novocastra. RESULTS: The percentage of immunopositive cells in particular fragments of the tumour ranged from 0--93%, mean 30.5%, median 25.5%. Mean and median values enabled division of children into two groups: Group A, where the percentage of cells staining with anti-PCNA was <30% and Group B, where this percentage was >30%. The expression of PCNA was evaluated in various stages of advancement, various histological types and depending on the course of disease. The studies revealed the correlation between index PCNA and stage of advancement P<0.01, index PCNA and histological type of Wilms' tumour P<0.025. Moreover we observed that deaths were found more frequently in tumours with index PCNA >30%, P<0.001. CONCLUSIONS: PCNA is a useful prognostic factor in Wilms' tumour in children.     

TPS检测对乳腺癌的诊断价值

目的:探讨组织多肽特异性抗原(TPS)检测在乳腺癌和乳腺癌术后转移复发的诊断价值.方法:对我院2008年6月至2009年12月行手术治疗的乳腺癌74例,乳腺癌术后转移复发8例,乳腺良性疾病72例全部应用酶联免疫吸附试验(ELISA)检测TPS.结果:乳腺癌和乳腺癌术后转移复发组明显高于乳腺良性疾病对照组(P＜0.01).结论:组织多肽特异性抗原(TPS)检测值对乳腺癌和乳腺癌术后转移复发是一观察指标,并与CA153,CEA等联合检测,更具有临床实用价值.     

Measurements of tissue polypeptide-specific antigen and prostate-specific antigen in prostate cancer patients under intermittent androgen suppression therapy.

The present study evaluated serial serum measurements of tissue polypeptide-specific antigen (TPS) in comparison with prostate-specific antigen (PSA) for assessment of tumour progression in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Twenty-three men were recruited into an IAS trial consisting of an initial 8 months of androgen suppression, followed by cycles of treatment cessation and resumption of therapy upon increases of PSA > 20 ng ml(-1) to prolong the hormone responsiveness of the tumour cells. Periods of androgen suppression resulted in reversible reduction in serum testosterone (< 1.8 nmol I(-1)) and PSA (< 4 ng ml(-1)) and decreases in tumour volume (mean reduction for first cycle 24 +/- 10%), indicating partial growth arrest and apoptotic regression of the tumours. In contrast to PSA values, non-specifically elevated TPS values were found in 8 of 23 patients. In 15 of 23 patients, TPS fell during periods of apoptotic tumour regression and increased simultaneously with testosterone and preceded the increases in PSA by 2 months during the period of treatment cessation. Although TPS represents a highly sensitive marker of tumour proliferation in this IAS clinical model of controlled tumour regression and regrowth, its low specificity compared with PSA limits its usefulness to monitoring of prostate cancer patients with proven absence of non-specific elevations of this marker.     

Cell types expressing the Wilms' tumour gene (WT1) in Wilms' tumours: implications for tumour histogenesis.

Wilms' tumour (nephroblastoma), a childhood embryonal kidney tumour, is believed to arise from malignant transformation of abnormally persistent metanephric blastemal cells. At a histological level, tumours show a remarkable mimicry of the normal nephrogenic pathway. There is histological and epidemiological evidence for at least two pathogenetic groupings within Wilms' tumour which may reflect different timings of the tumorigenic insult in this pathway and/or involvement of different genes. Tumorigenesis is thought to result from loss of function of a so-called tumour-suppressor gene which has an essential role in control of normal genitourinary development. Such a candidate, Wilms' tumour gene (WT1) mapping to chromosome 11p13, has been isolated and is known to be mutated in some tumours. We have examined the cell types expressing this gene in 32 Wilms' tumours and in nephroblastomatosis by in situ mRNA hybridization. Our results show that WT1 is expressed only in neoplastic structures whose normal counterparts also express the gene and that abnormally persistent high levels of expression are common in both these lesions. Thus, WT1 expression is a good marker for tumour differentiation and reveals how the normal pattern of differentiation is disrupted in Wilms' tumours. We postulate that mutation of the WT1 gene at the 11p13 locus results in Wilms' tumours associated with intralobar nephrogenic rests, which frequently show stromal-predominant histology. We have used our results and ideas to reinterpret current theories on tumour histogenesis and propose a model which explains how patterns of epithelial differentiation are disrupted in Wilms' tumour and how malignant stroma can result from mutation in WT1.     

DIAGNOSTIC VALUE OF SERUM PANCREATIC TISSUE CARCINOMA ANTIGEN IN PANCREATIC CARCINOMA

Serum pancreatic tissue carcinoma antigen (PCA) was measured by ELISA in 396 patients with pancreatic carcinoma (PC) and other diseases diagnosed by clinical examination, histopathology and operation. Serum PCA more than 300 U/ml was considered as diagnostic value for PC and 30-299 U/ml as probable index for PC. The sensitivity of PCA for PC was 78.2% (43/55), and the specifity 94.6%. The positive rate of PCA in other diseases were 0-13.3%. Combining the determination of PCA with B-mode ultrasonic scanning (BU). CT and/or ERCP (endos-copic retrograde cholangiopancreatography) may increase the diagnostic rate of PC to 89-91%, and with the "cocktail" of CA19-9, CEA (carcino-embryonic antigen) and RNase-C, PC be diagnosed in 88.9%. Therefore, it is suggest that PCA si a promising tumor market of PC with high sensitivity and relative specificity.     

Diagnostic value of mucin-like carcinoma-associated antigen (MCA) in breast cancer

The diagnostic value of mucin-like carcinoma-associated antigen (MCA) was compared to that of carcinoembryonic antigen (CEA) and/or CA 15.3 in patients with breast cancer. A total of 368 patients with breast cancer were studied, of whom 253 were free of metastases, whereas 94 had either skeletal or visceral metastases or diffuse metastatic disease. The diagnostic sensitivity of MCA proved to be comparable to that of CA 15.3 and superior to that of CEA in patients with metastatic breast cancer. In contrast, the specificity of MCA was superior to that of CA 15.3. Finally, the diagnostic sensitivity of each of the tested tumour markers, i.e. MCA, CEA and CA 15.3, could be improved by their combined use. We conclude that MCA, either alone or in combination with CA 15.3 and CEA, can improve the monitoring of disease progression in patients with metastatic breast cancer.     

SLIT2 promoter methylation analysis in neuroblastoma, Wilms' tumour and renal cell carcinoma

The 3p21.3 RASSF1A tumour suppressor gene (TSG) provides a paradigm for TSGs inactivated by promoter methylation rather than somatic mutations. Recently, we identified frequent promoter methylation without somatic mutations of SLIT2 in lung and breast cancers, suggesting similarities between SLIT2 and RASSF1A TSGs. Epigenetic inactivation of RASSF1A was first described in lung and breast cancers and subsequently in a wide range of human cancers including neuroblastoma, Wilms' tumour and renal cell carcinoma (RCC). These findings prompted us to investigate SLIT2 methylation in these three human cancers. We analysed 49 neuroblastomas (NBs), 37 Wilms' tumours and 48 RCC, and detected SLIT2 promoter methylation in 29% of NB, 38% of Wilms' tumours and 25% of RCC. Previously, we had demonstrated frequent RASSF1A methylation in the same tumour series and frequent CASP8 methylation in the NB and Wilms' tumour samples. However, there was no significant association between SLIT2 promoter methylation and RASSF1A or CASP8 methylation in NB and RCC. In Wilms' tumour, there was a trend for a negative association between RASSF1A and SLIT2 methylation, although this did not reach statistical significance. No associations were detected between SLIT2 promoter methylation and specific clinicopathological features in the tumours analysed. These findings implicate SLIT2 promoter methylation in the pathogenesis of both paediatric and adult cancers and suggest that further investigations of SLIT2 in other tumour types should be pursued. However, epigenetic inactivation of SLIT2 is less frequent than RASSF1A in the tumour types analysed.     

原发性乳腺癌患者治疗前血清TPS水平与预后之间的关系(英文)

Objective: The aim of this study was to explore the correlation of pretreatment serum tissue polypeptide specific antigen (TPS) with prognosis in primary breast cancer. Methods: A total of 361 patients with grades I-III breast cancer had been followed up from January 2001 to February 2011. Serumal TPS level was measured by enzyme-linked immunosorbent assays (ELISA). Univariate and multivariate analyses were used to investigate associations between pretreatment TPS level and clinicopathological parameters and patient outcomes. Results: First, at the univariate analysis, the expression of TPS was related with some clinicopathological traditional prognostic factors such as tumor size (P = 0.030), histologic grade (P = 0.001) and lymph node status (P = 0.008). Second, overall survival were significantly shorter among patients with elevated pretreatment serum TPS (P = 0.038). However, finally, multivariate Cox regression indicated that the level of pretreatment serum TPS was not an independent prognostic parameter for overall survival in primarily breast cancer patients (P > 0.05). Conclusion: The expression of pretreatment serum TPS is closely correlated with clinicopathology parameters and overall survival of patients with primarily breast cancer, but its level has no independent prognostic value.     

Somatic glypican 3 (GPC3) mutations in Wilms' tumour

Tumour and normal tissue from 41 male cases of Wilms' tumour were screened to determine the presence of sequence variants in the glypican 3 (GPC3) gene. Two non-conservative single base changes were present in tumour tissue only. These findings imply a possible role for GPC3 in Wilms' tumour development.     

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.     

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.     

The treatment of Wilms' tumour: results of the United Kingdom Children's cancer study group (UKCCSG) second Wilms' tumour study

The aims of the UKW2 study were: (1) to further refine treatment for stage I and II favourable histology (FH) patients; (2) to consolidate the UKW1 results for stage III FH patients; (3) to improve the outlook for patients with inoperable primary tumours and those patients with stage IV and unfavourable histology disease. Treatment consisted of primary nephrectomy, wherever possible, followed by chemotherapy and radiotherapy, as dictated by stage and histology. Treatment was refined successfully for stage I and II FH patients. The 4-year event-free survival for these two groups was 94% and 91%, respectively. Stage III FH patients had a 4-year event free survival of 84%. The outlook for patients with clear cell sarcoma of the kidney is as good as for patients with favourable histology, whilst that for patients with anaplastic or rhabdoid variants remains poor. The outlook for the majority of children with Wilms' tumour is now excellent.     

非小细胞肺癌患者血清TPS水平及其临床价值研究

目的:探讨血清TPS(组织多肽特异性抗原)水平与非小细胞肺癌(NSCLC)患者生物学特征的相关性及其临床应用价值.方法:采用ELISA法测定127例NSCLC患者和31例肺部良性肿瘤患者血清TPS水平,并以22例正常人血清作为对照.结果:NSCLC患者血清TPS水平高达377.2±302.5U/L,肺部良性肿瘤患者和正常对照组分别为109.7±51.9 U/L和71.6±33.8 U/L,NSCLC患者明显高于肺部良性肿瘤患者和正常对照组(P＜0.001),取正常值为148 U/L时,TPS对NSCLC诊断灵敏度是85%,特异度为84.9%;不同性别、年龄、病理类型之间和有无纵隔淋巴结转移NSCLC患者之间血清TPS水平接近,统计分析均无显著性差异(P＞0.05).TNM分期Ⅲ-Ⅳ期的病人血清TPS水平高达487.4±419.8U/L,明显高于Ⅰ-Ⅱ期病人(268.9±201.6 U/L);手术前患者(386.3±317.5 U/L)高于手术后(198.5±113.6 U/L)患者;复发后病人(552.3±471.6 U/L)明显高于复发前患者(204.2±133.7 U/L);存活期3年以上病人(266.3±242.2 U/L)明显低于存活期3年以内病人(489.5±353.3U/L),统计分析各组均有非常显著性差异(P＜0.001).结论:血清TPS水平与肿瘤活动度密切相关,能够反映疾病的严重程度,也可用于判定手术效果、监测复发和评估预后等.     

Upregulation of Wilms' tumour gene 1 (WT1) in uterine sarcomas

AimOverexpression of Wilms’ tumour gene (WT1) has been proven in several tumours. Previous research of our group on the cell cycle of uterine leiomyosarcoma (LMS) and carcinosarcoma (CS) suggested a possible role for WT1. We therefore intended to further explore the expression pattern of WT1 in uterine sarcomas.Methods27 CS, 38 LMS, 15 endometrial stromal sarcomas (ESS) and seven undifferentiated sarcomas (US) were collected. WT1 expression was evaluated by immunohistochemistry (IHC) in 87 samples, by RT-PCR (m-RNA expression) in 23 random selected samples and by Western blotting in 12 samples, separating cytoplasmic and nuclear proteins. A pilot study to detect mutations (exons 7–10) was performed on eight samples.ResultsIHC showed WT1 positivity in 12/27 CS, 29/38 LMS, 7/15 ESS and 4/7 US. All-but-one sample had a positive RT-PCR. All Western blottings were positive with more cytoplasmic expression in 9/12 cases. No mutations were found.ConclusionsWT1 is overexpressed in uterine sarcomas. Since increased levels of mRNA determine the biological role, WT1 might contribute to uterine sarcoma tumour biology.     

Tissue polypeptide-specific antigen and carcinoembryonic antigen for early prediction of recurrence in lung adenocarcinoma

Fifty patients with lung adenocarcinoma, including 20 cases with recurrence and 30 cases without recurrence 1 year after operation, were enrolled in this study. The serial serum levels of tissue polypeptide-specific antigen (TPS) and carcinoembryonic antigen (CEA) were measured before operation and at 1 week, and at 1, 3, 6, 9, and 12 months after operation for early detection of recurrence. The results revealed that: 1) mean serum values of TPS were significantly higher at 1, 3, 6, 9, and 12 months after operation in 20 patients with recurrent adenocarcinoma, when compared with 30 patients without recurrent adenocarcinoma; 2) mean serum values of CEA were significantly higher at 9 months and 12 months after operation in 20 patients with recurrent adenocarcinoma, when compared with 30 patients without recurrent adenocarcinoma. We conclude that TPS is a better marker than CEA for early prediction of adenocarcinoma recurrence in lung within 1 year after operation. However, a longer follow-up study should be encouraged.