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

Niho, Seiji; Nishiwaki, Yutaka; Goto, Kōichi; Ohmatsu, Hironobu; Matsumoto, T; Hojo, Fumihiko; Ohe, Yuichiro; Kakinuma, Ryutaro; Kodama, Tetsuro

doi:10.1016/s0169-5002(99)00100-2

Cited by 64 publications

(71 citation statements)

References 19 publications

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“…NSE was considered to be the representative tumor marker for small cell lung cancer (SCLC). None of these markers are ideal (11)(12)(13)(14)(15)(16)(17)(18). In this study, the levels of these tumor markers simultaneously increased in 2 patients, which indicates poor performance of these tumor markers in the diagnosis of SMPLC.…”

Section: Discussionmentioning

confidence: 66%

Early clinical diagnosis of synchronous multiple primary lung cancer

Xue

Wang

et al. 2011

Oncology Letters

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Abstract. The diagnosis of synchronous multiple primary lung cancer (SMPLC) remains a formidable challenge. The aim of the present study was to identify useful clues for the clinical diagnosis of SMPLC, in particular for the early stages. The medical records of 10 patients diagnosed with SMPLC with different histological types were analyzed retrospectively. Chest computed tomography (CT) findings showed two pulmonary lesions in all patients. The two lesions displayed malignant characteristics of primary lung cancer. The levels of a number of tumor markers, including carcinoembryonic antigen, neuron-specific enolase, cytokeratin fragment 21-1, squamous cell carcinoma and CA125 increased in 2 patients. Auxiliary examinations of other physical sites in these patients did not show signs of neoplasm metastasis. Two tumors were separately staged and appropriate treatment was carried out based on the revised stage, which provided more benefits for SMPLC patients. The diagnosis of SMPLC might be delayed or mistaken owing to its similarity to neoplasm metastasis. A high index of awareness is required for the early diagnosis of this disease. The malignant characteristics of primary lung cancer in various lesions may be valuable clues for the diagnosis of SMPLC. Alterations in the levels of tumor markers may be a poor diagnostic tool for the detection of SMPLC. Separate biopsies for different pulmonary masses should be performed for clinical staging as soon as possible and reasonable treatment based on the stage should also be selected.

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Section: Discussionmentioning

confidence: 66%

Early clinical diagnosis of synchronous multiple primary lung cancer

Xue

Wang

et al. 2011

Oncology Letters

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“…A recombinant version of ProGRP, comprising a carboxy-terminal region common to the three types of previously cloned human ProGRP molecules, has been synthesized, and an ELISA has been developed for its measurement in serum [15][16][17][18]. Preliminary results have shown the utility of ProGRP in the follow-up of SCLC patients [5,6,11,19]. Likewise, Stieber et al [8] reported ProGRP positivity in some NSCLC patients, but the highest ProGRP levels were found in SCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Pro-Gastrin-Releasing Peptide in Patients with Benign and Malignant Diseases

et al. 2004

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The specificity and sensitivity of pro-gastrin-releasing peptide (ProGRP) was evaluated in 37 healthy subjects, 197 patients with benign diseases and 310 patients with malignant diseases of different origins. Abnormal ProGRP serum levels (>50 pg/ml) were found in 10% of the patients with benign diseases and in 26.1% of the patients with active cancer. None of the healthy subjects had abnormal ProGRP levels. The benign disease with the highest ProGRP concentration was renal failure, with abnormal values in 51.6% of the patients studied. Excluding patients with renal failure or patients with creatinine levels greater than 1.5 mg/dl, raised ProGRP values (<80 ng/ml) were found in 2.5% (4/160) of patients with benign diseases and in 4.9% of patients with active malignancies other than lung cancer or neuroendocrine tumors (<110 ng/ml). Abnormal ProGRP serum levels were found in 26.2% of patients with non-small cell lung cancer (NSCLC) (mean 40.5 ± 35.4 pg/ml) and in 76.8% of patients with small cell lung cancer (SCLC) (mean 694 ± 1,776 pg/ml) (p < 0.001). ProGRP serum levels >300 pg/ml were only found in SCLC patients (41.4%). ProGRP results were related to tumor extension in SCLC (sensitivity in limited disease 58.3%, in extensive disease 95.5%) but not in NSCLC. In summary, renal failure is the most frequent source of false-positive results with ProGRP, and this marker is useful in the histological differential diagnosis of lung cancer.

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“…Many studies have shown that expression of different biomarkers are frequent in various histological types of lung cancers and many authors have considered the presence of these markers in serum as an index of extension of disease, prognosis and response to therapy (15). Some tumor markers have been extensively studied in lung cancer, such as carcinoembryonic antigen (CEA), SCC and cytokeratins CYFRA-21.1 are studied most extensively in non-small cell lung cancer (NSCLC) and neuron-specific enolase (NSE), ProGRP and chromogranin A in small cell lung cancer (SCLC) (16)(17)(18)(19)(20). However, application of these markers in diagnosis of lung cancers and in differentiating the histological types of the tumors has not been satisfactory, even though a relationship with clinical relevance has been found for the NSE and ProGRP markers in SCLC (18,19) and the CYFRA 21-1 marker, on the other hand, has been useful only in follow-up of NSCLC of the squamous subtype (21).…”

Section: Discussionmentioning

confidence: 99%

“…Some tumor markers have been extensively studied in lung cancer, such as carcinoembryonic antigen (CEA), SCC and cytokeratins CYFRA-21.1 are studied most extensively in non-small cell lung cancer (NSCLC) and neuron-specific enolase (NSE), ProGRP and chromogranin A in small cell lung cancer (SCLC) (16)(17)(18)(19)(20). However, application of these markers in diagnosis of lung cancers and in differentiating the histological types of the tumors has not been satisfactory, even though a relationship with clinical relevance has been found for the NSE and ProGRP markers in SCLC (18,19) and the CYFRA 21-1 marker, on the other hand, has been useful only in follow-up of NSCLC of the squamous subtype (21). In previous years, CD56 has become the antibody of choice in many laboratories because the sensitivities for other antibodies in small cell lung carcinoma vary, and comparative studies suggest that CD56 is the most sensitive in these markers for different diagnosing the SCLC from NSCLC (22,23).…”

Section: Discussionmentioning

confidence: 99%

Different expression of mimecan as a marker for differential diagnosis between NSCLC and SCLC

et al. 2009

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Abstract.Mimecan mRNA was present in a limited number of mouse and human tissues, however, abundant mimecan mRNA was observed in the lung tissue. Therefore, we hypothesize that mimecan could serve as a biomarker for differentiating various histological types of lung cancers. In humans, the mimecan mRNA was found most abundant in ovary and less abundant in lung by using Northern blot analysis. Moreover, the mimecan was expressed strongly in the epithelial cells of the bronchial wall and weaker in the epithelial cells of the alveolar sacs by in situ hybridization and immunohistochemical analysis. Furthermore, the mimecan immunoreactivity was found in 103 (97.2%) of 106 non-small cell lung cancers (NSCLCs). Nevertheless, a large majority of small cell lung cancers (SCLCs) (50/56, 89.3%) showed negative immunoreactivity to mimecan polyclonal antibody. A significant difference of mimecan immunoreactivity was found between NSCLC and SCLC (P<0.00001). This is the first study showing that mimecan could serve as an excellent pathological biomarker to distinguish NSCLCs from SCLCs. IntroductionMimecan/osteoglycin, isolated from bone, was originally called osteoinductive factor and later renamed mimecan/osteoglycin (1-3). It belongs to a family of small leucine-rich proteoglycans (SLRPs) that are secreted into the extracellular matrix. SLRPs, being abundant in bone matrix, cartilage cells and connective tissues, are important for collagen fibrillogenesis, cellular growth, differentiation and migration. The genomic structure of mimecan is highly conserved among species, a single copy gene gives rise to multiple mRNA transcripts, resulted from differential splicing and alternative polyadenylation (4). However, all mimecan mRNAs produce an identical protein that is conserved among mice, bovine, and human beings, suggesting its functional importance (3,5,6). The mimecan gene encodes a 34 kDa full-length protein which has been named mimecan. However, a 12-kDa mature protein corresponding to the 105 carboxyl-terminal amino acids of mimecan has been isolated from bovine bone (1,3,5); whilst a 25-kDa keratan sulfate glycoprotein corresponding to the 223 carboxyl-terminal amino acids of mimecan has been isolated from bovine cornea (3,7,8). Up to now, the physiological function of mimecan has not been fully elucidated. Initial studies showed that mimecan could induce ectopic bone formation and subcutaneous implantation of mimecan plus transforming growth factor ß (TGF-ß) type 1 or 2 into rats induced the bone formation at the implantation site (9). However, further study showed that co-purifying bone morphogenic proteins in mimecan preparation were the sources of the growth stimulatory activity (3). Interestingly, the tumor suppressor protein p53 could activate transcription of bovine and human mimecan genes (10-12). Furthermore, human mimecan mRNA was absent or at low levels in a majority of cancer cell lines and tumors, where p53 was frequently inactivated/mutated (10-12).In our recent study, we found that mimecan mRNA was present...

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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

Cited by 64 publications

References 19 publications

Early clinical diagnosis of synchronous multiple primary lung cancer

Early clinical diagnosis of synchronous multiple primary lung cancer

Pro-Gastrin-Releasing Peptide in Patients with Benign and Malignant Diseases

Different expression of mimecan as a marker for differential diagnosis between NSCLC and SCLC

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