Pro-gastrin-releasing Peptide Research Articles

Elevated serum progastrin-releasing peptide (31-98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer.

The neuroendocrine (NE) pathway has been attracting attention as a mechanism for the androgen-independent progression because the neuropeptide provokes tumor growth and inhibits apoptosis under androgen-deprived milieu in prostate cancer cells. On the basis that serum progastrin-releasing peptide (ProGRP) is elevated in patients with advanced disease stage, we examined the prognostic value of the neuropeptide. Serum ProGRP status was determined with an enzyme-linked immunosorbent assay (ELISA) in 460 men with benign and malignant prostatic diseases, chronic renal failure, and healthy controls. Seventy patients with metastatic prostate cancer including four patients (5.7%) with NE carcinoma who underwent hormonal therapy were enrolled in the prognostic analyses by Cox proportional hazards model. The serum status steadily shifted toward predominant expression of ProGRP with the progression of prostate cancer into metastatic and androgen-independent stages. Univariate analysis revealed that the deteriorated performance status (PS) and extent of bony disease (EOD), and high serum alkaline phosphatase (ALP), serum ProGRP, and nadir prostate-specific antigen (PSA) levels were associated with a lower progression-free survival (PFS) rate (P < 0.005). Multivariate analysis demonstrated that PS, serum ProGRP, and nadir PSA held an independent predictive value for PFS (P < 0.05), and all correlated with bone-related factors. Serum ProGRP was the most significant predictor among pre-treatment factors in this model (P = 0.0094). The neuropeptide precursor ProGRP is a distinct serum marker that is useful to know the NE milieu and provides prognostic information in patients with advanced prostate cancer. Standard therapy for metastatic prostate cancer may make progress when further studies will clarify the causative link between serum ProGRP level and androgen-independent disease progression.

A clinical study of ProGRP as a new tumor marker for small cell lung cancer

To evaluate the significance of progastrin-releasing peptide (ProGRP) as a new tumor marker for small cell lung cancer (SCLC).. Fifty-five patients with pathologically proved SCLC were initially treated and retrospectively studied, in which the level of serum ProGRP was tesed in various situations and its relationship with tumor stage and therapeutic effects was observed. The diagnostic sensitivity and specificity of ProGRP to SCLC were 80.0% and 97.0% respectively. The average ProGRP level in extensive disease of SCLC patients was 820.00 ng/L, significantly higher than 205.86 ng/L in limited disease of SCLC patients (P=0.000 3). In chemotherapy sensitive cases, the ProGRP level had a significant decrease after treatment, while there was no change in failure cases. ProGRP is a new SCLC tumor marker with high specificity and sensitivity. It has a close relationship with SCLC stage and can be used as a predictor of SCLC to chemotherapy response.

Diagnosis of Small Cell Lung Cancer by Pro Gastrin Releasing Peptide (ProGRP)/Diagnostik des kleinzelligen Bronchialkarzinoms mittels Pro Gastrin Releasing Peptide (ProGRP)

Article Diagnosis of Small Cell Lung Cancer by Pro Gastrin Releasing Peptide (ProGRP)/Diagnostik des kleinzelligen Bronchialkarzinoms mittels Pro Gastrin Releasing Peptide (ProGRP) was published on February 1, 2003 in the journal Journal of Laboratory Medicine (volume 27, issue 1-2).

Neuroendocrine and cytokeratin serum markers as prognostic determinants of small cell lung cancer

This retrospective study aimed at determining the prognostic significance of neuroendocrine markers chromogranin A (CgA), pro-gastrin releasing peptide (ProGRP) and neuron-specific enolase (NSE), together with the cytokeratin 19 marker CYFRA 21-1 in small cell lung cancer (SCLC). A total of 148 histologically proven and previously untreated SCLC patients were included. Among them 118 patients received a cisplatin–etoposide combination or cisplatin–etoposide–cyclophosphamide-4′-epidoxorubicin combination. All tumour markers were tested using immunoradiometric assays except for ProGRP which was tested using an enzyme-linked immunosorbent assay. The thresholds for marker serum titrations were 53 pg/ml, 65, 17, and 3.6 ng/ml for ProGRP, CgA, NSE and CYFRA 21-1 respectively. Univariate analysis showed that patients affected by one of the following characteristics proved to have a significant shorter survival in comparison with the opposite status of each variable: age over 63 years, extensive-stage, serum LDH level higher than 600 U/l, serum NSE level higher than 17 ng/ml, serum CgA level higher than 65 ng/ml and serum CYFRA 21-1 level higher than 3.6 ng/ml. In addition, there was a trend towards a statistical significance for a high serum alkaline phosphatase level and a performance status equal to or worse than two. The following variables were independent determinants of a poor outcome: a poor performance status (hazard ratio [95% confidence interval]: 1.51 [1.02–2.22]), a high CgA level (HR: 1.61 [1.06–2.45]), a high CYFRA 21-1 level (HR: 2.10 [1.40–3.14]) and an age older than 63 years (HR: 1.68 [1.14–2.48]). When the multivariate analysis was restricted to patients receiving a cisplatin–etoposide-based chemotherapy, the same variables were prognostic determinants with nearly similar hazard ratios. In conclusion, aside classical variables such as age and performance status, high serum CYFRA 21-1 and high serum CgA level in SCLC are both prognostic determinants of prognosis, in particular in patients receiving conventional chemotherapy consisting of cisplatin and etoposide-based combinations.

Expression of progastrin-releasing peptide and gastrin-releasing peptide receptor mRNA transcripts in tumor cells of patients with small cell lung cancer.

Small cell lung cancer (SCLC) is a rapidly growing neoplasm accounting for approximately 20% of patients with lung cancer. Progastrin-releasing peptide (proGRP) is produced in about two-thirds of SCLC tumors and is used as a specific marker for SCLC. Although GRP is known to have a variety of biological functions, only limited information is available concerning expression of proGRP mRNA and protein, and that of the receptor for GRP (GRPR) in SCLC tumors. In individuals with SCLC, the levels of serum proGRP(31-98) were measured by enzyme-linked immunosorbent assay. Expression of proGRP as well as GRPR mRNA in SCLC tumor tissues was investigated by reverse transcription-nested polymerase chain reaction (PCR) amplification. The proportions of alternatively spliced proGRP mRNA transcripts were analyzed in proGRP-producing tumors by nested and competitive PCR amplification. Finally, production of proGRP protein in SCLC tumor was evaluated by using immunohistochemical staining with a polyclonal human anti-proGRP antibody. ProGRP mRNA transcripts could be detected only in tumor tissues recovered from individuals with high serum proGRP levels. The proportions of mRNA subtypes in each case were nearly the same, revealing type I of 55.4+/-7.6%, type II with 21-b deletion of 1.8+/-3.6%, and type III with 19-b deletion of 42.8+/-4.3%, respectively. ProGRP protein production was demonstrated in tumor tissues exclusively from individuals exhibiting high serum proGRP levels. In contrast, GRPR mRNA transcripts were detectable in cancer cells from two of five proGRP-expressing tumor tissues. ProGRP mRNA expression is closely related with the synthesis of proGRP protein which is eventually released into the blood. It is suggested GRP may function as an autocrine growth factor for cancer cells in a subgroup of SCLC patients through, at least in part, upregulation of GRPR expression.

Serum pro-gastrin-releasing peptide (31-98) in benign prostatic hyperplasia and prostatic carcinoma

Objectives. To clarify whether serum levels of pro-gastrin-releasing peptide (ProGRP) (31-98) could be a useful marker in patients with prostatic carcinoma. GRP is produced and secreted by prostatic neuroendocrine cells. Methods. Serum levels of ProGRP(31-98) were measured by enzyme-linked immunosorbent assay in 20 patients with benign prostatic hyperplasia and 107 patients with prostatic carcinoma. Results. The mean serum levels of ProGRP(31-98) in patients with distant metastasis and hormone-resistant prostate cancer were significantly elevated compared with those in patients with organ-confined disease. Significantly elevated levels of ProGRP(31-98) were detected in 9 patients with prostatic carcinoma before any treatment. During hormone-resistant prostate cancer progression, ProGRP(31-98) levels were elevated in 9 patients (23%). Of the 9 patients with Stage D3 and elevated serum ProGRP, 4 had a normal serum prostate-specific antigen level. Conclusions. ProGRP may be a potential tumor marker for prostate cancer. Additional studies in large groups of patients are needed to define the clinical value of ProGRP.

Elevated serum progastrin-releasing peptide (31-98) in metastatic and androgen-independent prostate cancer patients.

Increases in neuroendocrine phenotype and secretory products are closely correlated with tumor progression and androgen independence in prostate cancer. In this study, we explored this correlation using serum progastrin-releasing peptide (ProGRP), a carboxy-terminal region common to three subtypes of precursors for gastrin-releasing peptide (GRP), which is released from the neuroendocrine phenotype to act as a growth factor. In 60 patients with benign prostatic hyperplasia (BPH) and 200 with prostate cancer, serum ProGRP levels were determined with an enzyme-linked immunosorbent assay (ELISA) kit and evaluated in relation to clinical stage, hormonal treatment, and prostate-specific antigen (PSA) values. Fourteen randomly selected patients were entered in the follow-up study. Additionally, expression of ProGRP as determined by immunohistochemical analysis was compared to that of chromogranin-A (CgA) in tissue samples from several subjects. We found a positive correlation between PSA and ProGRP in patients with untreated prostate cancer; no correlation was found in the treated groups. The increases in the ProGRP value and in the percentage of patients with higher than normal values were significant (P < 0.0001), especially in the androgen-independent group (P < 0.0001). A longitudinal study showed that, in a subset of patients, the ProGRP values tended to increase transiently when the cancer became androgen independent, but remained unchanged or decreased at the androgen-dependent stage. Positive staining for ProGRP occurred in a different distribution in neuroendocrine tissues than that of staining for CgA. The clinical results demonstrated the existence of a regulatory mechanism for GRP, which to date had only been observed in cell lines. These findings suggest that GRP is a growth factor potentially upregulated by androgen but that does not rely principally on androgen modulation. The large overlap in levels of ProGRP among the groups limits the use of this value as a monitoring tool. Measurement of ProGRP, however, does have potential as an independent parameter to evaluate androgen-independent progression and to facilitate a new therapeutic strategy that may compensate for current limitations of diagnosis based on PSA alone.

Complementary roles of pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase (NSE) in diagnosis and prognosis of small-cell lung cancer (SCLC)

In this study, we evaluated the clinical usefulness of ProGRP and NSE for diagnosis and prognosis of small-cell lung cancer (SCLC). Serum levels of ProGRP and NSE were determined in 108 healthy subjects, 103 patients with benign pulmonary diseases, 142 with non-small cell lung cancer (NSCLC), and 114 with SCLC. Sensitivity of ProGRP in diagnosis of SCLC was significantly higher than that of NSE (64.9 vs. 43.0%, P<0.001). The difference was substantial in patients with limited disease (56.5 vs. 20.3%, P<0.001). However, 11 of 40 SCLC patients with normal levels of serum ProGRP (27.5%) showed elevated levels of serum NSE. In the SCLC patients receiving chemotherapy, the CR rate in patients with elevated NSE levels was significantly lower than in patients with normal levels of NSE (18.5 vs. 61.7%, P<0.001). Elevation of both ProGRP and NSE was a poor prognostic factor, and patients with elevated levels of either ProGRP or NSE showed shorter survival than those without. From multivariate analysis, NSE was found to have a greater effect on survival of SCLC patients than ProGRP. These findings indicate that ProGRP is more sensitive than NSE for diagnosis of SCLC, while NSE is superior to ProGRP as a prognostic factor. In conclusion, both ProGRP and NSE are useful tumor markers and they have a complementary role for each other in diagnosis and prognosis of SCLC.

Pro-gastrin-releasing peptide, neuron specific enolase and chromogranin A as serum markers of small cell lung cancer

Background: Small cell lung cancer (SCLC) yields neuroendocrine properties. Pro-gastrin-releasing peptide (ProGRP), neuron specific enolase (NSE) and chromogranin A (CGA) are therefore putative serum markers in this disease. Aim: To assess any difference in the sensitivity–specificity relationship between these neuroendocrine markers regarding various control populations and disease extent. Method: A total of 146 patients were prospectively assessed clinically and biologically. Serum marker titrations were performed using commercial immunoradiometric assays (NSE, CGA) or ELISA (ProGRP). Areas under receiver operating characteristic curves (AUC-ROC) were calculated in order to assess the sensitivity–specificity relationship of each marker and to compare marker accuracy. Maximum Youden indices were used to determine marker thresholds able to produce the best overall diagnostic information. Results: Assessing the sensitivity in the SCLC population and the specificity in benign lung disease, ProGRP demonstrated the best sensitivity relationship in as much as its AUC-ROC was significantly greater than the ones calculated using NSE and CGA (respective values, 0.95, 0.89, 0.70; two-tailed Z-test <0.05). The ProGRP threshold value, which offered the best sensitivity–specificity relationship was 53 pg/ml corresponding to a 0.80 sensitivity and a 0.96 specificity. In addition, when specificity was assessed in NSCLC and again the sensitivity in the whole SCLC population, ProGRP continued to demonstrate a greater AUC-ROC in comparison with other markers. Using the 53 pg/ml threshold the specificity of this marker was excellent with no false positives in NSCLC. On the other hand, none of the markers were able to discriminate limited from extensive SCLC as suggested by the fact that AUC-ROC, constructed when sensitivity was defined as a positive test in extensive disease and specificity as a true negative test in limited disease, did not reach the upper left octant (AUC 0.65, 0.71 and 0.63 for ProGRP, NSE and CGA, respectively). Conclusion: ProGRP yields the best sensitivity–specificity feature in SCLC, a result deserving further studies designed to evaluate the clinical applicability of this marker.

Significance of serum pro-gastrin-releasing peptide as a predictor of relapse of small cell lung cancer: comparative evaluation with neuron-specific enolase and carcinoembryonic antigen

Neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) have been reported to be useful markers for staging, monitoring treatment, and predicting relapse in patients with small cell lung cancer (SCLC). Recently, pro-gastrin-releasing peptide (Pro-GRP) became available as a sensitive, specific, and reliable tumor marker for patients with SCLC. The aim of this study is to determine the most useful tumor marker to detect the relapse of SCLC. Furthermore, we analyzed the relationship between tumor markers at relapse and survival from relapse or response to salvage chemotherapy. Medical records were reviewed to obtain serum levels of Pro-GRP, NSE, and CEA before and after the initial chemotherapy, and at relapse. Consecutive 66 patients with SCLC, with an objective response and confirmed relapse treated at the National Cancer Center Hospital East, were analyzed in this study. The percentages of patients whose tumor marker level were elevated before treatment, decreased after the treatment, and increased again at relapse were 67% (95% CI, 55–78) for Pro-GRP, 20% (10–29) for NSE, and 38% (26–50) for CEA. Multivariate analysis indicated that poor performance status before initial treatment and elevated serum levels of lactate dehydrogenase at relapse were poor prognostic factors for patients with recurrent SCLC ( P<0.005). None of the serum levels of Pro-GRP, NSE, and CEA at relapse was a significant prognostic factor and associated with an objective response to salvage chemotherapy. The present study demonstrated that serum levels of Pro-GRP reflect the disease course of patients with SCLC most accurately.

Primary primitive neuroectodermal tumor of the lung: report of two cases

Two cases of primitive neuroectodermal tumor of the lung are reported. The first case is a 41-year-old man with a tumor in the left upper lung, and the second case is a 30-year-old woman with a tumor in the right lower lung. In both cases, the tumors originated in the lung but not in the chest wall. No distant metastasis was detected. In case 1, transcutaneous fine-needle biopsy (TCNB) revealed small round cell proliferation, although bronchoscopic examination showed no abnormal findings. Both the expression of Mic2 protein and t(11; 22)(q24; q12) translocation were proved in the tumor cells. The tumor cells were positive for periodic acid-Schiff (PAS), neuron-specific enolase (NSE), and vimentin, but negative for Leu7, chromogranin A, and pro-gastrin-releasing peptide (ProGRP). In case 2, bronchoscopic examination showed only compressive change in right lower lobe bronchi. TCNB revealed small round tumor cells expressing Mic2 protein. The tumor cells were negative for leukocyte common antigen, S100 protein, pankeratin, chromogranin A, and desmin, but weakly positive for NSE and moderately positive for KI-67 (MIB1). Both patients were successfully treated by the combination of surgical resection and chemotherapy, and are alive with no sign of recurrence for approximately 22 months in case 1 and 16 months in case 2.

Serum Pro-Gastrin-Releasing Peptide Is a Useful Marker for Treatment Monitoring and Survival in Small-Cell Lung Cancer

We investigated the usefulness of serum pro-gastrin-releasing peptide (Pro-GRP) as a tumor marker for diagnosis, treatment monitoring and the prediction of relapse and prognosis in patients with small-cell lung cancer (SCLC). Serum samples were obtained from 127 patients with primary lung cancer (48 patients with small-cell carcinoma, 31 with adenocarcinoma, 36 with squamous cell carcinoma and 11 with large-cell carcinoma). The cutoff levels of serum Pro-GRP and neuron-specific enolase (NSE) were set at 46 pg/ml and 10 ng/ml, respectively. The specificity of Pro-GRP was significantly higher than that of NSE (Pro-GRP: 93.7%, NSE: 65.8%, p < 0.01). According to the histological type of lung cancer, the positive rates of Pro-GRP were 75% (36/48) in the small-cell carcinomas, 9.7% (3/31) in the adenocarcinomas, 5.6% (2/36) in the squamous cell carcinomas and 0% (0/10) in the large cell carcinomas. The median levels of Pro-GRP in limited disease (LD) and extensive disease (ED) patients were 199 and 295.5 pg/ml, whereas those of NSE were 14.8 and 29.3 ng/ml, respectively. The positive rates of Pro-GRP in LD and ED patients were 80.0% (16/20) and 71.4% (20/28), whereas those of NSE were 70.0% (14/20) and 89.3% (25/28), respectively. The positive rate of NSE tended to elevate with the progression of disease, whereas that of Pro-GRP was already high at an early stage. Among the 29 patients with SCLC who could be followed, the serum Pro-GRP levels of 18 responders were significantly decreased after treatment (p < 0.01), whereas those of the 11 nonresponders were not significantly different between before and after treatment (p = 0.72). In the 9 patients with SCLC who relapsed, the serum Pro-GRP levels were again elevated at the time of relapse. Seventeen patients whose ratio of the Pro-GRP level after treatment to the level before treatment was below 50% (taking the levels before treatment as 100%) survived significantly longer than did the patients whose ratio was over 50% (p < 0.01). The results of the present study suggest that serum Pro-GRP has high specificity and could be a useful marker of SCLC for treatment monitoring and prognosis.

CYFRA 21-1 and ProGRP, tumor markers of lung cancer, are elevated in chronic renal failure patients.

Serum levels of CYFRA 21-1(cytokeratin-19 fragment) and ProGRP (pro-gastrin-releasing peptide), the new prognostic markers of lung cancer, were measured by ELISA (enzyme-linked immunoadsorbent assay) in 27 (for CYFRA 21-1; male 13, female 14; age 54+/-17 years) or 22 (for ProGRP; male 9, female 13; age 59+/-18 years) patients with various serum creatinine levels, 42 haemodialysis (HD) patients (male 24, female 18; age 59+/-14 years) and 30 continuous ambulatory peritoneal dialysis (CAPD) patients (male 18, female 12; age 48+/-9 years). All the patients were without clinical and radiological signs of lung cancer. Positive correlations were found between serum creatinine and serum CYFRA 21-1 and ProGRP levels. Serum levels of CYFRA 21-1 were above the cutoff limit (3.5 ng/mL) in 57% of HD patients (mean 4.07+/-1.56 ng/mL) and in 73% of CAPD patients (mean 4.87+/-1.56 ng/mL). Serum levels of ProGRP were above the cutoff limit (46.0 pg/mL) in 90% of HD patients (mean 107.0+/-59.4 pg/mL) and in 93% of CAPD patients (mean 112.4+/-44.5 pg/mL). Our data indicate that evaluation of renal function is essential when the measurement of these tumor markers is to be applied as one of the diagnostic tools of lung cancer.

Clinicopathologic characteristics of patients with nonsmall cell lung carcinoma with elevated serum progastrin-releasing peptide levels.

Progastrin-releasing peptide (proGRP) is a specific tumor marker in patients with small cell lung carcinoma (SCLC). It has been reported that serum proGRP levels rarely are elevated in patients with nonsmall cell lung carcinoma (NSCLC); the reported frequency is <3%. The purpose of this study was to examine the clinicopathologic features of NSCLC patients with high serum proGRP levels. The authors measured serum proGRP levels with a TND-4 kit, a newly developed enzyme-linked immunoadsorbent assay, in 544 NSCLC and 206 SCLC patients. Pathologic features were examined using conventional hematoxylin and eosin staining and histochemical and immunohistochemical staining using polyclonal antibodies to proGRP, chromogranin A, calcitonin, and monoclonal antibody to the neural cell adhesion molecule (NCC-Lu-243). The serum proGRP levels were elevated in 140 SCLC patients (68.0%) and in 23 NSCLC patients (4.2%). Seven of these 23 NSCLC patients had serum proGRP levels > or = 100 pg/mL. They included two patients with renal dysfunction, one patient diagnosed cytologically with adenocarcinoma without undergoing precise pathologic examination, two patients diagnosed histologically with squamous cell carcinoma with foci of small cell elements, and two patients diagnosed with large cell neuroendocrine carcinoma and poorly differentiated adenocarcinoma, respectively, which showed neuroendocrine differentiation on immunohistologic analysis. The remaining 16 NSCLC patients had serum proGRP levels < 70 pg/mL. Nearly all NSCLC patients had serum proGRP levels < 100 pg/mL. However, if an NSCLC patient presents with a proGRP level > or = 100 pg/mL, the clinicopathologic features must be examined with regard to the small cell component, neuroendocrine differentiation, and renal dysfunction.

Serum levels of five tumor markers for lung cancer in patients with chronic renal failure.

The soluble cytokeratin 19 fragment (CYFRA) and pro-gastrin-releasing peptide (ProGRP) are recently described promising tumor markers for lung cancers. To assess their alterations in renal dysfunction, serum levels of CYFRA and ProGRP were determined together with conventional markers including carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron specific enolase (NSE) in patients with renal failure of varying degrees. The mean concentration of all these markers but NSE significantly increased with the severity of renal failure. After hemodialysis (HD), the mean concentration of ProGRP, the molecular weight of which is comparable to that of 2-microglobulin, was significantly decreased. High false positive rates for tumor markers of lung cancer in patients with renal failure should be considered to avoid unnecessary diagnostic procedures.

Age-related changes of serum progastrin-releasing peptide levels during childhood.

Gastrin-releasing peptide (GRP) has attracted much attention in recent years because it has become recognized as a significant tissue-specific growth factor. To investigate the physiological significance of this peptide in growing children, the time course of serum ProGRP(31-98) level, a precursor hormone of GRP, in children was assessed. A total of 118 serum samples including cord blood was examined with informed consent by using a specific enzyme-linked immunosorbent assay (ELISA) system to measure serum ProGRP(31-98). The serum ProGRP(31-98) level was highest in cord blood and neonatal samples, rapidly declined by 1 year of age and then gradually declined to the adult level by 5 years of age. This time-dependent change of serum ProGRP(31-98) level suggests the importance of GRP as a physiological growth factor in fetal and neonatal tissues.

Progastrin-releasing peptide(31-98) in idiopathic pulmonary fibrosis and sarcoidosis.

Gastrin-releasing peptide (GRP) is present in the lung and functions as a growth factor for bronchial epithelial cells and fibroblasts. GRP may stimulate release of cytokines from alveolar macrophages. However, in interstitial lung diseases, the role of GRP has not been clarified, in part because of the instability of GRP. Progastrin-releasing peptide (ProGRP) molecules are the actual GRP gene products. ProGRP molecules contain common extension peptides(31-98) [ProGRP(31-98)], which are not homologous with other proteins unlike GRP. With the ELISA, we measured ProGRP(31-98) concentrations in sera and bronchoalveolar lavage (BAL) fluids from patients with sarcoidosis and idiopathic pulmonary fibrosis (IPF). Significant increased ProGRP(31-98) concentrations were found in sera and BAL fluids from patients with IPF or sarcoidosis when compared with healthy subjects. Serum ProGRP(31-98) values significantly correlated with BAL fluid ProGRP(31-98) values. In IPF and sarcoidosis, the release of the actual GRP gene products is increased in the lung and the bloodstream, and GRP may play a role during the processes of inflammation and remodeling in interstitial lung diseases.

Elevated progastrin-releasing peptide(31–98) concentrations in pleural effusions due to small-cell lung carcinoma: Shijubo N, Hirasawa M, Sasaki H, Igarashi T, Fujita A, Kodama T et al. Third Department Internal Medicine, Medical University School Medicine, South-1, West-16, Chuo-ku, Sapporo 060. Respiration 1996;63:106–110

Elevated progastrin-releasing peptide(31–98) concentrations in pleural effusions due to small-cell lung carcinoma: Shijubo N, Hirasawa M, Sasaki H, Igarashi T, Fujita A, Kodama T et al. Third Department Internal Medicine, Medical University School Medicine, South-1, West-16, Chuo-ku, Sapporo 060. Respiration 1996;63:106–110

Elevated progastrin-releasing peptide(31-98) concentrations in pleural effusions due to small-cell lung carcinoma.

Progastrin-releasing peptide (ProGRP) is a specific and actively secreted product from small-cell lung carcinoma (SCLC) cells. Recently, an enzyme-linked immunosorbent assay, which uses monoclonal and polyclonal antibodies to recombinant proGRP(31-98), a common region of ProGRP, was established. We measured concentrations of ProGRP (31-98), neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) in carcinomatous and infectious pleural effusions. Significantly increased ProGRP(31-98) and NSE values were found in carcinomatous pleurisy due to SCLC compared to the other carcinomatous pleurisy and infectious pleurisy. CEA values were significantly increased in carcinomatous pleural effusions compared with those in infectious effusions. The ProGRP(31-98) values were not correlated to NSE values in carcinomatous pleurisy due to SCLC. The determination of ProGRP(31-98) in pleural effusions will be helpful for diagnosing carcinomatous pleurisy due to SCLC.

Enzyme immunoassay of immunoreactive progastrin-releasing peptide(31-98) as tumor marker for small-cell lung carcinoma: development and evaluation

Previously, using recombinant human progastrin-releasing peptide (ProGRP)(31-98), we developed a RIA for ProGRP(31-98) and demonstrated that the determination of serum ProGRP(31-98) was a reliable marker for small-cell lung carcinoma (SCLC) (Miyake et al., Cancer Res 1994;54:2136-40). Aiming for a more convenient assay system, we have now developed and evaluated a highly sensitive and specific ELISA for ProGRP(31-98). Only 50 microL of nonextracted serum is needed, and results are obtained in only 2 h. Intraassay and between-day CVs were 1.7-4.6% and 4.2-6.8%, respectively. The log-log calibration curve was linear to 1000 ng/L, and analytical recovery was 91.5-108.7%. The detection limit of this assay, 1.9 ng/L, means that basal concentrations of ProGRP(31-98) were detectable in all healthy subjects. The cutoff value, based on the mean + 3 SD of concentrations in 247 healthy subjects, was set to 45.1 ng/L. Serum concentrations exceeded this value in 18 of 25 SCLC patients, similar to the frequency of increased values found by RIA previously. In contrast, the frequency of increased serum ProGRP(31-98) in patients with nonmalignant pulmonary diseases or non-SCLC was quite low: 0% and 5.0%, respectively. Such results may justify a clinical trial for evaluating this ELISA for the diagnosis and monitoring of SCLC patients.