Tumor markers--personal experience. Immunohistochemical markers for cancer diagnosis

Immunohistochemical tumor markers have been increasingly utilized for histopathological diagnosis. Major applications include: 1) Differential diagnosis of undifferentiated tumors, 2) identification of primary site of metastatic carcinoma of unknown primary, 3) analysis of tumor differentiation, 4) functional study of functioning tumors, and 5) assessment of tumor aggressiveness. Since many antigens can be detected in routinely processed formalin-fixed tumor tissues, immunohistochemistry is a very useful tool to analyze the relationship between phenotypic characteristics and morphology. It is expected that many more immunohistochemical markers will become available for histopathological diagnosis.     

Tumor markers--personal experience. Multidisciplinary treatment of disseminated germ cell tumor in full use of tumor markers]

The ideal course of multidisciplinary treatment of disseminated germ cell tumors was shown with special reference to the role of the tumor markers for 1) diagnosis of pathological elements and risk factors, 2) appropriate selection of the protocol before and during the chemotherapeutic treatment, 3) timely resection of residual tumor and 4) monitoring of the recurrence after treatment. The practical role of tumor markers for evaluation of chemotherapeutic effectiveness, the following reconsideration of the appropriate protocol and timely indication of surgical intervention for residual mass after chemotherapy were emphasized by demonstrating the clinical courses of 2 patients with advanced nonseminomatous testicular germ cell tumors.     

Tumor markers--personal experience. A case report of primary lung cancer with interesting production of tumor markers

Three interesting cases of primary lung cancer from the standpoint of tumor marker production were reported. The first was a case of double cancers, one of which was sigmoid cancer without CEA production and the other a large cell lung cancer with CEA production. The evidence of elevated serum CEA level initially led to a wrong diagnosis as sigmoid cancer with lung metastasis. The second was a case which showed a relapse of monotonous cancer without CEA production after surgical removal of lung cancer tissue containing heterogeneous cancer cells. Elevated serum CEA levels were never observed after the operation, although the preoperative serum test was positive for CEA. The last was a case of squamous cell lung cancer which showed trophoblastic differentiation accompanied with massive hCG production. Very rapid tumor cell growth was seen after the early relapse following the operation. Positivity for hCG staining varied among primary and metastatic tumor tissues.     

Tumor markers--personal experience. How to read time course of some values and tumor marker doubling time

Tumor marker doubling time is based on essential exponential curve of it. In this paper, we studied significance of tumor marker doubling time about 3 point: 1) time course of values, 2) Cancer growth, 3) Correlation between cancer growth and tumor marker. And we introduce the clinical application of tumor marker doubling time as a evaluation of survival time after chemotherapy, and the easy method of calculation of tumor marker doubling time.     

Tumor marker--screening for gynecological cancer; personal experience. Utility of tumor markers in screening of ovarian cancer

PAP smears and biopsies are very effective in mass screening for uterine cancer. However, in this study, we tried to determine whether tumor markers could be useful for ovarian cancer screening. Eight tumor markers (CA125, TPA, CEA, ALP, amylase, LDH, CRP, IAP) were tested in serum samples from 3,540 women and the values were supplied to a CAMPAS (computer aided multivariate and pattern analysis system). Using this system, we managed to reduce the false positive rate to 0.68% but we couldn't prove the sensitivity of this system, because there were no ovarian cancer cases in this group. At this time, it is important to determine the high risk group of ovarian cancer for reducing the cost of mass screening. Finally, if tumor markers are to become more effective for ovarian cancer screening, it will be necessary to find ones that are more sensitive to ovarian cancer.     

Tumor markers--personal experience. A case of advanced extragonadal germ-cell tumor showing complete remission by high-dose combination chemotherapy with autologous bone marrow transplantation]

A twenty-four-year-old male patient with stage III advanced extragonadal germ-cell tumor obtained complete remission after comprehensive treatment including high-dose combination chemotherapy with autologous bone marrow transplantation. He had massive tumors in cervical, mediastinal, abdominal and inguinal lymph nodes, bilateral lungs and liver. Ascites, plural effusion and pericardial effusion were also noted. Cancer cells were demonstrated from his bloody sputum, pericardial drainage and an aspirate from supraclavicular tumor. His tumor produced hCG, AFP, placental ALP and LDH, and hCG was the best marker for the diagnosis and monitoring. The initial serum hCG level was high at 460,000 mIU/ml, but fell to 13 mIU/ml after 3 courses of PVP therapy. However, it rose ten-fold in a week. After ultra-high dose combination chemotherapy with autologous BMT, the patient's hCG fell to 1.8 mIU/ml and remained at that level thereafter. He has remained well with no sign of recurrence after 25 months.     

Tumor markers in lung cancer]

Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA), and pro-gastrin-releasing peptide (proGRP) can be used as tumor markers for lung cancer. CEA is sensitive for adenocarcinoma, SCC and CYFRA for squamous cell carcinoma, and NSE and proGRP for small cell carcinoma. A tumor marker is generally used as a marker to monitor the clinical course. Serum levels of pro-GRP, reflect the disease course of patients with small cell lung cancer more accurately than NSE or CEA. Among the patients with clinical N0-1 non-small cell lung cancer high serum CEA levels, adenocarcinoma histology, and large tumor dimension were significant predictors of pathologic N2 disease. CEA played a new role in predicting metastasis to mediastinal lymph nodes A more effective treatment may enhance the value of tumor markers to predict relapse.     

Tumor markers for cancer detection. I

We report a prospective study aimed at assessing the value of serum marker determinations in a supposedly healthy population to detect cancer and to identify individuals at high risk. We analyzed a group of 1,611 supposedly healthy subjects attending a cancer detection center, over a 1-5 year period and a control group of 100 cancer patients. Repeated determinations of the following markers were made: CEA, AFP, HCG, beta-HCG, beta 2-M, ferritin, beta 1-SP, all by radioimmunoassay. In the literature, marker determinations are considered not to be useful for cancer screening; in spite of this, we determined "normal" and "suspicious" levels for each marker and were able to define a group "at risk" that may harbor an early cancer (representing 23.6% of the total) and a "normal" group. The cancer detection rate was 45 0/00 (17/378) in the risk group and 3.2 0/00 in the "normal" one (4/1233). Our data show that markers could play a role in cancer screening.     

Tumor markers for cancer detection. II

Updated results of a prospective study assessing the value of tumor marker determinations in a supposedly healthy population (2,000) for identification of a group at risk for cancer are reported. With observation periods varying from 1 to 6 years (mean 3.5 years), repeated determinations by RIA were routinely carried out for CEA, AFP, beta-HCG, beta 2-M, ferritin, and, more recently, beta 1-SP. Preliminary data on TPA, CA 12-5, and CA 19-9 were also obtained. A comparative study of methods for CEA determination using monoclonal and polyclonal antibodies revealed that preference should be given to polyclonal antibodies. In the group considered to be "at risk" (ie, having at least one abnormal marker value) (N = 481), the cancer detection rate was 29 per 1,000 against 3.2 per 1,000 in the normal group (N = 1,519). These figures were significant, even if the number of malignancies detected was small (N = 27). By associating general tumor markers such as CEA, TPA, and CA 19-9 with site-specific markers such as PAP and CA 12-5, it seemed that marker determinations played a useful role in risk assessment in cancer detection programs.     

Tumor markers for colorectal cancer

CEA and CA19-9 are the two most common tumor markers for colorectal cancer that are currently utilized clinically. The positive rate of CEA is 40-60% and that of CA19-9 is 30-50%. Simultaneous use of the two markers is useful in evaluating the therapeutic effect and monitoring the recurrence of advanced colorectal cancer. Surgical specimens may also provide useful information for the appropriate treatment of patients. Using surgically resected lymph nodes, we examined micrometastasis to assess the spread of the cancer cells and the malignant potential of colorectal cancer. Immunohistochemical analysis using anti-cytokeratin antibody revealed no significant impact of micrometastasis on patient prognosis, while RT-PCR assay using CEA as a genetic marker suggested a positive value in predicting a rapid recurrence. Among various molecular markers, we found that CDC25B phosphatase was a powerful prognostic factor for colorectal cancer. Diagnosis of the existence and malignant potential of cancer cells, together with serum tumor marker levels, may help to construct a more useful system for the better treatment of colorectal cancer.     

Tumor markers--personal experience. Ha-ras P21 in neuroblastoma: a new marker associating to patient's prognosis

Neuroblastoma is a disease with wide spectrum clinically For the evaluation of the biological specificity of this tumor, we examined the expression of Ha-ras p21. The Ha-ras p21 detected in tumor cells showed a statistically significant association with the non-progressed tumor at the diagnosis and the favourable outcome of the patients. The association of Ha-ras p21 with their clinical outcome was closer than those of N-myc amplification. However, the complementary analyses of both Ha-ras p21 and N-myc gene seemed to provide more precise informations relating the patient's care.     

Mining the tumor phosphoproteome for cancer markers.

Despite decades of cancer research, mortality rates remain high largely due to the failure of early detection, poor understanding of the epidemiology of rational drug targets, and molecular etiology of human cancers. The discovery of disease markers promises to deliver some solutions to these formidable challenges. Gene and protein expression profiling through DNA microarray and proteomics have already made a tremendous effect in this area. However, protein/gene expression does not necessarily reflect protein activity, which is often regulated via post-translation modifications, of which phosphorylation is one of the most prominent. This is an important consideration because the activity of protein is a more relevant phenotype than its expression during pathogenesis. Tyrosine kinases represent a very important class of enzymes that are critical regulators of mitogenic and angiogenic signaling, hence attractive targets for anticancer drugs as exemplified by BCR-ABL and ErbB2. More than 50% of them are overexpressed or mutated resulting in a gain of function in various human cancers. In this review, we discuss the potential effect of phosphoproteins as cancer markers in cancer diagnosis and therapeutics. Phosphoproteomics strategies that might pave the way to high-throughput analysis for routine clinical applications are also described.     

Clinical usefulness of tumor markers for the diagnosis of ovarian cancer]

The most useful diagnostic methods for ovarian cancer at present are diagnostic imaging and measurement of tumor markers. Although many tumor markers have been measured to detect patients with ovarian cancer, the values of diagnostic efficiency are not so high when a single tumor marker is assessed. Therefore, the use of a combination of tumor markers might be expected to yield a higher value. In this study, tumor markers were measured to select an ovarian cancer group from a group in which ovarian tumor was palpable by the pelvic examination. We selected CA 602 from core-protein related markers, CA 54/61 from sugar chain core-related markers, and galactosyltransferase associated with tumor (GAT) for their combined use from among eleven markers examined. As a result, the combined use of each two markers or of all three markers appeared to be beneficial to discriminate ovarian cancers from benign ovarian tumors. The combination of all three markers gave a somewhat higher positive rate and diagnostic efficiency value than that of the two markers. The role of tumor markers in the future screening of ovarian cancer was also discussed in this paper.     

Tumor markers of childhood cancer

Tumor markers are the substances which are produced from malignant cells and are detectable from peripheral blood or body fluid. These markers are used for the evaluation of treatment effectiveness or the detection of relapse. In most cases of pediatric cancer, specific molecular abnormalities of tumor cells have been able to be identified. Evaluation of these molecular markers is critical for the diagnosis and the choice of treatment. Recently, these molecular markers have also come to be used for the detection of minimal residual disease. Such a system can be regarded as a kind of tumor marker.     

Tumor markers of pancreatic cancer

To determine the clinical usefulness for diagnosis and monitoring of pancreatic tumor markers, serum levels of CA 19-9 (RIA; less than or equal to 37U/ml), POA (EIA; less than 11 U/ml), CEA (EIA; less than or equal to 4.4 ng/ml) and TPA (RIA; less than or equal to 110 U/ml) were measured in 57 patients with pancreatic cancer and 25 patients with benign diseases of the pancreas. Frequencies of elevation for pancreatic cancers were 73.9% for CA 19-9, 69.2% for POA, 48.9% for CEA and 73.2% for TPA. Furthermore, the frequencies of elevation at relatively early stages of pancreatic cancer were not high. It was therefore thought that these markers were unsuitable for early diagnosis of pancreatic cancers. Although serum levels of CA 19-9 and POA in cases of pancreatic cancer were distributed up to on extremely high level, those for benign diseases of the pancreas were located up to twice the values of the cut-off levels. Therefore, these two markers seem promising for differentiating preoperatively between pancreatic cancer and benign diseases of the pancreas. CA 19-9 and POA were also useful for monitoring the recurrence of pancreatic cancer. In particular, patients with high preoperative levels seem good candidates for postoperative monitoring.     

Surgical treatment of cancer of the digestive organs

Recently the surgical treatment for cancer of digestive organ has made remarkable progress. This development depends on the progress of diagnosis, instrument, operation procedure and management. I will state on the principle of oncological surgery, stage classification, minor surgery, major surgery and multidisciplinary treatment. And I will mention about latest trend of surgical treatment for cancer.     

Standards, options and recommendations for tumor markers in colorectal cancer]

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the French National Federation of Comprehensive Cancer Centers (FNCLCC), the 20 French Cancer Centers and specialists from French Public University or General Hospitals, and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome of cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of the main tumor markers in colorectal cancer and their potential role in the management of patients with this malignancy. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 117 independent reviewers, and to the medical committees of the 20 French Cancer Centers. RESULTS: The main recommendations for the tumor markers in colorectal cancer are: 1) The carcinoembryonic antigen (CEA) is the reference serum marker (standard). 2) All the analyses for a given patient must be performed in the same laboratory, using the same technique (standard, expert agreement). 3) CEA or CA 19-9 should not be used for screening or diagnosis (standard, level of evidence B2). 4) High initial serum concentration of CEA is of bad predictive value (standard, level of evidence C). CEA is an independent prognostic factor of survival in colorectal cancers with lymph node metastases (standard, level of evidence B2). 5) CEA is the most sensitive biological parameter for the screening of hepatic metastases (standard, level of evidence B2). 6) CEA serum concentration before palliative chemotherapy is an independent prognostic factor of survival (standard, level of evidence B2). The combination of CEA assay with imagery techniques and clinical examination can help monitor the response to palliative chemotherapy (standard), in particular in non measurable disease (standard, expert agreement). 7) In 65% of the cases, CEA is the first indicator of relapse (standard, level of evidence B2). CEA is the choice marker for monitoring patients with colorectal cancer (standard, level of evidence B2). 8) A sustained biological follow-up including CEA assay can be used to predict the operability of recurring tumors (standard, level of evidence B2). Nevertheless, no survival advantage has been shown (standard).     

胰腺癌血清肿瘤标志物研究进展

胰腺癌病程进展迅速,早期诊断困难.目前,糖类抗原19-9(CA19-9)仍是使用最为广泛的胰腺癌诊断及复发监测血清肿瘤标记物.近年来,蛋白质组学研究的发展,为寻找新的肿瘤标志物提供了新的途径.血清中肝癌-小肠-胰腺/胰腺炎相关蛋白(HIP/PAP-1)、磷酸甘油酸酯激酶、钙网织蛋白、DJ-1和热休克蛋白(HSP)27等因蛋白质组学研究技术的应用而被鉴定,为胰腺癌的早期微创诊断带来希望.