Value of serum calcitonin estimation in clinical oncology.

In 132 consecutive patients with carcinoma of various organs, a higher serum immunoreactive calcitonin (ICT) concentration (median level 50 pg/ml) was found than in 68 normal subjects (median level 20 pg/ml). The incidence of hypercalcitoninaemia was 40%. All 9 patients with primary liver-cell carcinoma were hypercalcitoninaemic. On the other hand, none of the 7 patients with a carcinoma of the breast had raised ICT levels. In bronchogenic cancer a relationship between ICT and cell type was found, with a predominance of high ICT in patients with oatcell and other undifferentiated types, whereas in squamous-cell carcinomas and adenocarcinomas of the lung hypercalcitoninaemia was relatively rare. When we divided all our patients according to differentiation of the tumour cell, it was found that the lower the degree of differentiation, the higher the ICT concentration, whereas opposite results were observed for CEA. When ICT and CEA were estimated concurrently, we found at least one marker increased in 70% of our patients. Our results demonstrate that patients with metastases in the liver have more frequently and increased ICT. In addition, we conclude that lifespan can be expected to be lower in patients with high ICT levels. In a longitudinal study of 46 patients, there was a positive correlation between change in serum ICT and tumour mass.     

Imaging studies and the prognostic value of serum calcitonin in staging small-cell lung cancer

The controversial prognostic significance of serum calcitonin in small-cell lung cancer (SCC) prompted this retrospective study relating serum levels to (1) stage of disease [limited disease (LD) vs. extensive disease (ED)], (2) imaging studies of metastases to bone, liver, and brain, and (3) survival. Of the 127 previously untreated patients with SCC presenting from 1979 to 1984, calcitonin levels could be compared to the stage of the disease in 69 patients (25 LD and 44 ED) and to various staging procedures including 99mTc methylene diphosphonate bone scans (63 patients), 99mTc sulfur colloid liver-spleen scans (64 patients), computed tomography of the head (63 patients) and serum calcium (61 patients). 71% (49/69) of patients had elevated calcitonin of whom 65% (32/49) had ED. 29% (20/69) had normal levels of whom 60% (12/20) had ED. 40% (18/45) of patients with raised calcitonin had liver metastases. 100% (19/19) with normal calcitonin had no liver involvement. Two patients with hypercalcemia and increased calcitonin had extensive bony metastases. The survival experiences of patients with normal and elevated serum calcitonin levels were analyzed. No significant differences were found within each stage or in the group overall. The positive correlation of serum calcitonin to liver metastases was statistically significant. No such relationship could be demonstrated with stage of disease, bone metastases, brain metastases, or survival.     

Humoral markers for thyroid carcinoma

We investigated the usefulness and limits of serum thyroglobulin, serum calcitonin, and serum tissue polypeptide antigen as humoral markers for thyroid carcinoma in 364 patients with papillary, follicular, medullary, and undifferentiated types of thyroid cancer. In agreement with other studies we found that serum thyroglobulin was a specific and sensitive marker for well-differentiated thyroid cancer after total thyroidectomy. Lymph node, lung, and bone metastases were associated with high serum thyroglobulin concentrations, both during and after thyroid-suppressive therapy with L-thyroxine. Serum thyroglobulin determination was superior to whole body scanning in predicting the presence of differentiated metastases, because patients with nonfunctioning metastases and negative whole body scan also had high levels of serum thyroglobulin. Serum calcitonin levels were increased in all patients with active medullary thyroid cancer, confirming the specificity of this marker in detecting tumors arising from parafollicular C-cells. Furthermore, in medullary thyroid cancer serum tissue polypeptide antigen levels were also increased in most patients. This last substance was found to be increased also in undifferentiated thyroid cancer. Of particular interest was the finding of increased serum tissue polypeptide antigen levels in 15 cases of differentiated thyroid cancer, whose metastases underwent a progressive process of "dedifferentiation."     

The use of carcinoembryonic antigen and peptide hormones to stage and monitor patients with lung cancer

Carcinoembryonic antigen (CEA) and the peptide hormones adrenocorticotropin (ACTH), calcitonin, parathormone (PTH), beta-human-chorionic gonadotropin β-hCG), growth hormone (hGH), and prolactin were determined in more than 100 patients with lung cancer before and during therapy. CEA values were increased in 51% of lung cancer patients at diagnosis. The peptide hormones ACTH, calcitonin, PTH, and β-hCG showed elevated levels with a frequency of about 20 to 50%. The highest hormone levels were found in patients with oat cell carcinoma. In contrast to CEA, peptide hormone levels did not correlate with the clinical stage of disease. Serial determinations of CEA and peptide hormones showed the usefulness of these tumor markers for monitoring therapy.     

A study of immunoreactive calcitonin (CT), adrenocorticotropic hormone (ACTH) and carcinoembryonic antigen (CEA) in lung cancer and other malignancies

Levels of immunoreactive ACTH and calcitonin (CT), as well as CEA, were determined serially in 144 patients with lung cancer and in 62 patients with metastatic carcinoma to the lungs. Patients with neoplasms not involving the lungs, with nonmalignant blood dyscrasias, and with chronic obstructive pulmonary disease were studied, as were normal control subjects. In 55-91% of lung cancer patients, elevated values of CT were detected; the frequency of elevation varied with cell type and stage. The highest values (mean 1346 +/- 2534 pg/ml) were found in patients with extensive small cell lung carcinoma (SCLC) and were significantly greater than the values for patients with SCLC confined to one hemithorax (196 +/- 287.7 pg/ml, P less than 0.005). ACTH levels were elevated less frequently (24-46%) and were highest (192 +/- 200.9 pg/ml) in patients with extensive small cell carcinoma, although Cushing's syndrome was observed only once. Agreement between all three tumor markers was seen in 25-50% of lung cancer patients; the percentage depended on cell type. Calcitonin levels paralleled changes in the clinical status and tumor burden in 89% of SCLC patients, while ACTH levels reflected the clinical course in 67%. In six patients with small cell carcinoma in remission, rising levels of CT, ACTH, and CEA preceded clinical evidence of relapse, in oe patient, by as long as five months. Among 129 patients with conditions other than primary lung cancer, CT levels were highest (232 +/- 328 pg/ml) in those with cancer metastatic to the lungs and/or pleura; there was no; association between CT levels and the presence of bone metastases.     

Monoclonal antibody CM-H-9 detects circulating placental isoferritin in the serum of patients with visceral metastases of breast cancer

The aim of the current pilot study was to determine whether placental isoferritin (PLF) can be detected in the serum of patients with metastatic breast cancer. Sera were obtained from breast cancer patients with metastatic disease (n = 100), from breast cancer with no evidence of disease (n = 70) and from healthy female controls (n = 34). PLF and total serum ferritin levels were independently measured using specific monoclonal antibody ELISAs in a double-blind study. It was found that the mean serum PLF levels were significantly elevated only in patients with visceral metastases (lung, liver, brain) compared with the levels of patients with non-visceral metastases (bone, skin) or with healthy controls. Contrary to this, analysis of total serum ferritin levels did not reveal significant differences between these groups. Considering 0-10 units/ml as a PLF negative result, it was found that PLF was negative in 87.5% of healthy controls and in 96% of breast cancer patients with no evidence of disease. In contrast, PLF was positive in 73% of the patients with visceral metastases and in 29.7% of those with non-visceral metastases. The striking difference between visceral and non-visceral metastases is not yet understood. It could result from a difference in the degree of vascularisation or, alternatively, a difference in the cell types and genes expressed by cells metastasizing to visceral or non-visceral organs.     

Immunocompetence in lung cancer. Relationship to extent of tumor burden and histologic type

In vitro assays of immunocompetence were done in 60 patients with differing extents of tumor load and various histologic types of lung cancer and were compared to values obtained for 60 normal controls. Profound alterations in monoclonal antibody-defined T-lymphocytes and circulating B-cells were seen. All patients showed impaired blastogenic response to the mitogens used with the exception of a normal response to pokeweed mitogen (PWM) in patients with localized disease. Increase levels of serum IgG were seen in patients with localized disease whereas high levels of IgA was seen in patients with more advanced disease. Distant metastases were associated with low IgM levels. All patients studied regardless of stage and histologic type had elevated levels of circulating immunocomplexes. These findings indicate gross immunologic abnormalities in these patients.     

Calcitonin as a marker for bronchogenic cancer: a prospective study.

A prospective study was done of serum calcitonin (HCT) levels in 61 patients with bronchogenic cancer. Initially, 52% of patients had hypercalcitonemia. Hypercalcitonemia was not confined to patients with any particular histologic type. Seventy-eight percent of those with high calcitonin remained normocalcemic. There was no correlation between high calcitonin levels and osseous metastases. Selective thyroid venous sampling delineated two types of hypercalcitonemia: thyroidal and ectopic. To date, the ectopic type has been associated with the small cell bronchogenic carcinoma. High initial calcitonin levels decreased significantly in 75% of patients on antitumor therapy. In 13 evaluable patients calcitonin levels mirrored clinical status changes 67% of the time. Calcitonin may be a useful marker to assess the results of therapy in patients with bronchogenic cancer.     

原发性肺癌患者外周血内皮抑素检测意义

目的 :研究原发性肺癌患者外周血内皮抑素 (endostatin)的含量水平与肺癌临床病理因素的关系。方法 :用ELISA法对 79例原发性肺癌、8例肺部良性疾病及 2 0例健康人血浆内皮抑素含量进行分析。结果 :血浆内皮抑素含量在原发性肺癌、肺部良性疾病及健康人分别为 (9 3± 5 7)pg mL、(6 3±2 5 )pg mL、(4 9± 3 2 )pg mL ,肺癌明显高于肺部良性疾病和健康人 ,P <0 0 5 ;血浆内皮抑素含量在Ⅰ、Ⅱ、Ⅲ、Ⅳ期肺癌中分别为 (6 6± 4 3)pg mL、(7 1± 5 5 )pg mL、(8 7± 6 0 )pg mL、(10 6± 4 5 )pg mL ,血浆内皮抑素含量与肺癌临床分期有关 ,P <0 0 5 ;年龄≥ 6 0岁肺癌患者血浆内皮抑素含量为 (7 9± 4 2 )pg mL ,年龄 <6 0岁为 (10 4± 5 6 )pg mL ,后者明显高于前者 ,P <0 0 1。结论 :原发性肺癌患者外周血内皮抑素含量水平显著高于正常对照 ,且与肿瘤分期和淋巴结转移有关     

Serum-soluble receptor-binding cancer antigen expressed on SiSo cells as a clinical marker in lung cancer

The aim of this study was to explore the diagnostic value of levels of the serum-soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) expressed in lung cancer patients. Enzyme-linked immunosorbent assay was performed to detect serum sRCAS1 levels in 138 patients with lung cancers of various types and in 40 healthy controls. Our results showed that the patients with lung cancer had higher serum sRCAS1 levels than the controls. As disease stages progressed in lung cancer, serum sRCAS1 levels increased; patients with lymph node and distant metastases had higher levels than those without metastases, regardless of histology, age, and gender. At a cutoff value of 19.2 U/ml, sRCAS1 was 91.3 % sensitive and 72.5 % specific for lung cancer. In conclusion, these results suggest that sRCAS1 levels could have a clinical value for the diagnosis and management of lung cancer and could be used as a new tumor marker of lung cancer.     

Tumor associated glycoprotein-72 (TAG-72) levels in patients with non-malignant and malignant disease.

TAG-72 is a tumor-associated antigen identified by the monoclonal antibody B72.3. Serum levels of TAG-72 were measured in patients with non-malignant and malignant disease. TAG-72 is not a specific marker of cancer and slightly elevated levels of this antigen can also be detected in the serum of healthy subjects. However, our results show that specificity (92%) and positive predictive value (86%) of this marker are very high. TAG-72 levels above the cut-off limit of 6 U/mL were found in patients with tumors of various organs, including gastrointestinal, ovarian, lung and breast cancer. TAG-72 assay sensitivity is related to tumor stage with values being highest with advanced disease, especially in patients with gastric cancer and lung adenocarcinoma.     

Mucin-like carcinoma-associated antigen: sensitivity and specificity in metastatic breast cancer

The clinical usefulness of a tumor marker essentially depends on its sensitivity and specificity for a certain tumor. To prove, wheather the new tumor marker 'mucin-like carcinoma-associated antigen' could be used for the management of breast cancer patients, we determined its serum concentration in 50 healthy blood donors, 130 patients with various non-malignant diseases, 138 patients with different metastazised tumors and 137 breast cancer patients. 78 of the breast cancer patients had known metastases while 59 had no evidence of disease after initial surgical and adjuvant therapy. Only 2% of the blood donors and 3% of the patients with non-malignant diseases exceeded the cut-off level of 15 U/ml. In contrast to these findings, 28% of patients with various metastazised tumors and 77% of patients with metastazised breast cancer had serum levels above 15 U/ml. Breast cancer patients without evidence of disease had elevated marker values in only 3%. In breast cancer the serum levels of this antigen depends on the type of metastases. Maximal concentrations were found in mixed metastases while cutaneous or lymph-node metastases showed the lowest rate of positivity. Furthermore a good correlation of serial determined marker levels with the course of the disease was observed, so that we conclude, that mucin-like carcinoma-associated antigen can be used in follow-up of patients with metastazised breast cancer. Because of its high sensitivity and specificity it provides some advantage over other markers used in this disease.     

The L1210 assay for immune complexes: application in cancer patients and correlation with disease progress

Immune complexes (ICs) were determined by the non-complement-dependent L1210 radioimmune assay on 132 serum samples collected from 53 patients with a variety of cancers. Both the mean IC levels and frequency of positive tests were significantly greater in cancer patients (mean = 96 +/- 100 microgram/ml, 46% positive) than in a control group of 67 normal healthy blood donors (mean = 39 +/- 15, 3% positive). When cancer patients were assorted into groups by disease progress, those with large or progressing tumors had significantly higher mean values (136 +/- 129) and frequency of positives (75%) than those with small or regressing tumors (58 +/- 18, 22% positive). In lung cancer patients, IC levels showed a strong inverse correlation (rs = -0.903) with survival time in patients who died, and appeared to be a better prognostic indicator than performance status (Karnofsky scale) at time of diagnosis. Serial IC measurements taken on several patients showed a decrease in levels concomitant with a favorable response to cytoreductive therapy, sustained normal levels during periods of prolonged remission, and a rise to elevated levels with (and sometimes preceding) documentation of new metastases.     

原发性肺癌患者外周血内皮抑素检测的临床意义

目的:研究原发性肺癌患者外周血内皮抑素的含量水平与肺癌临床病理因素的关系。方法:用ELISA法对79 例原发性肺癌、8 例肺部良性疾病及20 例健康人血浆内皮抑素含量进行分析。结果:血浆内皮抑素含量肺癌组明显高于肺部良性疾病和健康人,差异具有显著性(P<0.05);血浆内皮抑素含量与肺癌临床分期有关(P<0.05);年龄≥60 岁肺癌患者血浆内皮抑素含量明显高于年龄<60 岁肺癌患者,且差异有显著性(P<0.01)。结论:原发性肺癌患者外周血内皮抑素含量水平显著高于正常对照,且含量与肿瘤分期有关。     

Alkaline phosphatase level increase with initiation of hormone therapy for prostate cancer portends poor prognosis with rapid progression to bone metastases: a case report and review of the literature

A 73-year-old man with localized prostate cancer was treated with androgen deprivation and radiation therapy. Staging evaluation showed no evidence of metastatic disease. After initiation of androgen deprivation therapy, the patient developed a marked increase in serum alkaline phosphatase (ALP). Despite continuation of hormonal ablation and completion of radiation therapy, ALP and prostate-specific antigen levels continued to increase. Bone metastases were documented 6 months after diagnosis. In this report, we explore the role of serum ALP as an indicator for patients who develop early metastases and thus might benefit from early initiation of aggressive secondary treatments such as chemotherapy.     

TPS in breast cancer--a comparative study with carcinoembryonic antigen and CA 15-3.

The serum levels of tissue polypeptide antigen were determined using the M3 monoclonal antibody (TPS) and compared with the serum levels of carcinoembryonic antigen (CEA) and breast carcinoma antigen 15-3 (CA 15-3) in 96 patients with benign breast tumors, in 25 breast cancer patients with no evidence of disease, in 139 preoperative breast cancer patients and in 298 samples of 25 breast cancer patients during therapy monitoring (4-22 samples per patient). The 95th percentile of TPS in 89 apparently healthy females was 51 U/l. The 95th percentile of TPS in patients with benign breast tumors was 55 U/l. The maximum TPS level in breast cancer patients with no evidence of disease was 56 U/l. In preoperative breast cancer the number of patients with TPS levels above the 95th percentile of TPS in benign breast tumors was significantly higher in stage III breast cancer as compared with stage I+II. This was not established for CEA and CA 15-3. During therapy monitoring TPS followed the course of the disease faster than CEA and CA 15-3 in patients with bone metastases, liver metastases, lung metastases and pleural effusion, with one exception. TPS levels could be correlated with progression of disease in patients with normal and steady levels of CEA and/or CA 15-3.     

Serum BMP-2 Up-regulation as an Indicator of Poor Survival in Advanced Non-small Cell Lung Cancer Patients

Purpose: High levels of bone morphogenetic protein (BMPs) have been reported in patients with lung cancer.This study was conducted to assess correlations between serum BMP-2 levels and prognostic outcome in patientswith non-small-cell lung cancer (NSCLC). Methods: Blood samples from 84 patients with advanced NSCLCand 42 healthy controls were analyzed and quantitated for serum BMP-2 levels before and after two cycles ofchemotherapy using a commercially available ELISA kit. Results: The median level of BMP-2 was 146.9 pg/ml in patients with NSCLC vs. 87.7 pg/ml in healthy controls (P<0.01). A significant correlation was observedbetween pretreatment serum BMP-2 level and ECOG PS, disease stage and number of organs with metastases(P<0.05). Serum BMP-2 level decreased significantly in patients who achieved objective response after twocycles of chemotherapy. Multivariate analysis showed that increased BMP-2 level and advanced clinical stagewere significantly correlated with poor prognosis. Conclusion: Thes erum BMP-2 level is positively correlatedwith clinical stage, ECOG PS and metastatic burden and may serve as an independent negative predictor forprognosis. Decreased BMP-2 after chemotherapy could be a reliable marker for efficacy of treatment.     

Availability of tumor-antigen 4 as a marker of squamous cell carcinoma of the lung and other organs

The serum level of tumor-antigen 4 (TA-4) was measured in 401 patients with squamous cell carcinoma (SCC) of various organs (76 lung, 82 esophagus, and 234 head and neck). The mean serum level of TA-4 in patients with lung SCC was 3.6 times higher than that in healthy controls and even higher in the advanced stages of disease (III, IV). In patients with benign diseases or other types of lung cancer, however, the TA-4 serum level was not different from the controls regardless of the clinical stage. During radiation therapy, the TA-4 levels in patients with lung SCC decreased with reduction in tumor size. It increased again markedly during recurrence. Similarly, patients with SCC of the esophagus and head and neck also showed elevated TA-4 levels but only at advanced stages and in recurrence. It was concluded that TA-4 is highly related to SCC not only of the uterine cervix but also of other organs and that serum level determinations are useful for monitoring therapeutic effects and recurrence of these diseases, despite some limitations.     

Clinical evaluation of seven tumour markers in lung cancer diagnosis: can any combination improve the results?

In this study we compared the diagnostic utility of: (1) neuron-specific enolase (NSE); (2) squamous cell carcinoma antigen (SCC); (3) carcinoembryonic antigen (CEA); and (4) cytokeratin markers (CYFRA 21-1, TPA, TPM, TPS) in patients with small-cell lung cancer (SCLC) (21 cases) and non-small-cell lung cancer (94 cases). For comparison we also studied 66 patients with benign lung diseases and nine with pleural mesothelioma. NSE levels in SCLC patients were significantly higher than those in all the other groups studied. No significant variations were found among the SCC levels in all groups. CEA levels in patients with adenocarcinoma were significantly higher than those in all other groups studied. CYFRA 21-1 serum levels significantly increased in patients with squamous cell carcinoma and mesothelioma, while TPA, TPS and TPM increased in patients with lung cancer irrespective of the histological type. In patients with SCLC, high levels of all markers except SCC were found when the disease was extensive. In patients with non-SCLC, the highest levels of all tumour markers were usually found in those with advanced disease, although CYFRA 21-1 gave a sensitivity of 44% when a specificity of 95% was fixed in stage I non-SCLC patients. An analysis of receiver operating characteristic curves revealed that the highest diagnostic accuracies in distinguishing benign from malignant lung diseases were achieved with TPM (81%), CYFRA 21-1 (72%), CEA (78%) or TPA (78%) when using cut-off values of 46 Ul-1, 3.0 micrograms l-1, 2.0 micrograms l-1 and 75 Ul-1 respectively. When all patients were considered, the combined evaluation of more than one marker did not significantly improve the results obtained with TPM alone. However, taking into consideration the fact that CYFRA 21-1 is the most sensitive index of early lung tumours and that its combined determination with TPM did not worsen the overall sensitivity and specificity of the latter, the combined use of these two markers may be suggested as a useful took for the diagnosis of lung tumours.     

Glycoproteins and human cancer. 1. Circulating levels in cancer serum.

Total protein and sialic acid levels were determined in the supernatant of serum treated with perchloric acid. Patients with either localized or advanced metastatic malignancy have significantly elevated mean serum values. The highest levels occur in patients with lung, GI, GYN cancer, lymphoma and malignant melanoma. Patients with leukemia and multiple myeloma have slightly elevated values, but they were not significantly different from normal. Patients following curative surgery have normal values while patients in clinical remission following chemotherapy have elevated mean serum protein and NANA levels. Elevated values also occur in patients with benign tumors and 12% of patients with nonmalignant disease. Tumor cells appear to shed macromolecules which contribute to the observed elevation of serum protein and sialic acid levels.