Markers For Diagnosis Of Lung Cancer Research Articles

Potential for trans-pulmonary tumor markers in the early diagnosis of lung cancer: a case report

BackgroundMeasurement of tumor markers from peripheral venous blood is an emerging tool to assist in the early diagnosis of lung cancer. Samples from the pulmonary artery and pulmonary artery wedge position (trans-pulmonary samples) are accessible via right-heart catheterization and, by virtue of their proximity to lung tumors, may increase diagnostic yield.Case presentationWe report a case of a 64 year-old woman from whom trans-pulmonary samples were obtained and who was diagnosed 16 months later with recurrent metastatic small cell lung cancer. Carcinoembryonic antigen, cytokeratin fragment 21 − 1 (CYFRA), and human epididymis protein 4 (HE4) levels demonstrated increasing concentrations across the pulmonary circulation. These gradients exceeded the assays’ coefficient of variation by several-fold. For CYFRA and HE4, pulmonary artery wedge concentrations exceeded peripheral venous levels by more than 10% and peripheral arterial levels were up to 8% higher than peripheral venous levels.ConclusionsEvaluating the feasibility and utility of trans-pulmonary tumor markers for lung cancer diagnosis in a larger cohort should be considered. The addition of a peripheral arterial sample to standard peripheral venous samples may be a more practical alternative.

Improved diagnostic accuracy with three lung tumor markers compared to six-marker panel.

Combining multiple tumor markers increases sensitivity for lung cancer diagnosis in the cost of false positive. However, some would like to check as many as tumor markers in the fear of missing cancer. We though to propose a panel of fewer tumor markers for lung cancer diagnosis. Patients with suspected lung cancer who simultaneously underwent all six tests [carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA), squamous cell carcinoma-associated antigen (SCC), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and sialyl Lewis-X antigen (SLX)] were included. Tumor markers with significant impact on the lung cancer in a logistic regression model were included in our panel. Area under the curve (AUC) was compared between our panel and the panel of all six. We included 1,733 [median 72 years, 1,128 men, 605 women, 779 (45%) confirmed lung cancer]. Logistic regression analysis suggested CEA, CYFRA, and NSE were independently associated with the lung cancer diagnosis. The panel of these three tumor markers [AUC =0.656, 95% confidence interval (CI): 0.630-0.682, sensitivity 0.650, specificity 0.662] had better (P<0.001) diagnostic performance than six tumor markers (AUC =0.575, 95% CI: 0.548-0.602, sensitivity 0.829, specificity 0.321). Compared to applying all six markers (at least one marker above the upper limit of normal), the panel with three markers (at least one marker above the upper limit of normal) led to a better predictive value by lowering the risk of false positives.

The value of folate receptor-positive circulating tumour cells as a diagnostic biomarker for lung cancer: a systematic review and meta-analysis.

To conduct a systematic review and meta-analysis evaluating the diagnostic value of folate receptor-positive (FR+) circulating tumour cells (CTCs) as a potential tumour marker for lung cancer diagnosis. The PubMed, Embase, and Web of Science databases were searched for relevant articles published between database inception and November 2022. Eligible studies were selected based on inclusion and exclusion criteria. Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve (AUC) were pooled with 95% confidence intervals (CI), using RevMan 5.4 and STATA 17.0 software to assess the diagnostic value of FR+CTC for lung cancer. After screening, 11 studies involving 3469 subjects were eligible for inclusion. The pooled sensitivity and specificity were 0.79 (95% CI 0.76, 0.82) and 0.84 (95% CI 0.81, 0.96), respectively, and the pooled positive and negative likelihood ratios were 4.90 (95% CI 4.25, 5.65) and 0.25 (95% CI 0.22, 0.29), respectively. The pooled diagnostic odds ratio was 19.70 (95% CI 16.06, 24.16). The AUC of the pooled summary receiver operating characteristic curve was 0.89 (95% CI 0.85, 0.91). Sensitivity analysis showed that this result was stable after one-by-one study elimination. Folate receptor-positive CTCs may have good diagnostic value in lung cancer.

Is hypermethylation of SOX1 gene an independent prognostic marker in surgically resected non-small cell lung cancer?

Promoter hypermethylation of tumor suppressor genes presents promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine the association between the promoter hypermethylation of multiple genes and 5-year survival rate in patients with Non-small cell lung cancer (NSCLC). Primary tumor samples (n = 65), corresponding nonmalignant lung tissues (n = 65), and circulating blood were obtained from NSCLC patients who underwent curative surgery. Promoter methylation status in seven genes (RASSF1A, CDH13, MGMT, ESR1, DAPK, SOX1, and HOXA9) was quantified by using bisulfite pyrosequencing. Five-year survival data were obtained by a clinician. Cox proportional hazards models were used to analyze the associations between gene methylation status and overall patient survival. The 5-year survival of the patients with SOX1 aberrant tumor methylation was found to be statistically significantly shorter than for those patients without aberrant tumor methylation (P = 0.01). This effect was independent of TNM stage. No significant survival differences were associated with aberrant methylation in other genes tested in either of the two tissue types. Our study shows that SOX1 promoter hypermethylation in NSCLC tumors is significantly associated with inferior survival, showing promise as a useful prognostic biomarker in patients with NSCLC.

Role of complement activation product C4d as a predictor biomarker in lung cancer diagnosis

Background Molecular biomarkers such as complement C4d in bronchoalveolar lavage (BAL) may interfere with lung cancer diagnosis. However, limited studies have been conducted. The authors aimed to study the role of complement C4d as a predictive marker for lung cancer diagnosis. Participants and methods This case–control study included 45 participants: 30 were diagnosed as patients with lung cancer, comprising 16 with non-small cell lung cancer (NSCLC) and 14 with small cell lung cancer (SCLC), and 15 apparently healthy individuals as a control group. All patients (group I) were subjected to chest radiography, chest computed tomography, and flexible bronchoscopy. Forceps biopsies and BAL were taken for histopathological and cytological examination and measurement of C4d levels. For all participants, sputum and blood samples were collected for C4d measurement. Results There were statistically significant higher complement C4d levels in serum (P=0.006) and sputum of patients with lung cancer versus control group (P&lt;0.001). There was no statistically significant difference in complement C4d level between NSCLC and SCLC in the three samples (P=0.315 for BAL, 0.7 for serum, and 0.744 for sputum). Complement C4d has a high sensitivity and specificity in serum and BAL for lung cancer prediction. Conclusion Complement activation product C4d biomarker could be used as a predictor of lung cancer diagnosis; however, it cannot differentiate between its two major subtypes: NSCLC and NSCLC.

Identification of lung cancer gene markers through kernel maximum mean discrepancy and information entropy

BackgroundThe early diagnosis of lung cancer has been a critical problem in clinical practice for a long time and identifying differentially expressed gene as disease marker is a promising solution. However, the most existing gene differential expression analysis (DEA) methods have two main drawbacks: First, these methods are based on fixed statistical hypotheses and not always effective; Second, these methods can not identify a certain expression level boundary when there is no obvious expression level gap between control and experiment groups.MethodsThis paper proposed a novel approach to identify marker genes and gene expression level boundary for lung cancer. By calculating a kernel maximum mean discrepancy, our method can evaluate the expression differences between normal, normal adjacent to tumor (NAT) and tumor samples. For the potential marker genes, the expression level boundaries among different groups are defined with the information entropy method.ResultsCompared with two conventional methods t-test and fold change, the top average ranked genes selected by our method can achieve better performance under all metrics in the 10-fold cross-validation. Then GO and KEGG enrichment analysis are conducted to explore the biological function of the top 100 ranked genes. At last, we choose the top 10 average ranked genes as lung cancer markers and their expression boundaries are calculated and reported.ConclusionThe proposed approach is effective to identify gene markers for lung cancer diagnosis. It is not only more accurate than conventional DEA methods but also provides a reliable method to identify the gene expression level boundaries.

Copy number variation of genes in cell-free DNA in patients with lung adenocarcinoma.

e24060Background: The problem of early diagnosis of lung cancer remains unsolved since currently known molecular markers for lung cancer diagnosis do not possess necessary specificity. Studying gen...

IGFBP-4 expression is adversely associated with lung cancer prognosis.

Insulin-like growth factor binding protein-4 (IGFBP-4) was reported to be associated with prognosis in several types of cancer; however, to the best of our knowledge, whether it is correlated with lung cancer has yet to be reported. In the present study, 102 pairs of lung cancer tissues and surrounding non-cancerous tissues (SNCTs) were collected. The IGFBP-4 levels in tissues were detected with immunohistochemistry. The relevance of IGFBP-4 to the survival of patients was assessed. The IGFBP-4 gene was knocked down, and its function in the proliferation of lung cancer cells was measured. The percentage of lung cancer tissues with higher IGFBP-4 expression than SNCTs (51.9%) was increased compared with the percentage with similar (11.76%) or lower (36.27%) IGFBP-4 expression. Patients with higher IGFBP-1 expression exhibited a shorter median survival time. IGFBP-1 was associated with metastasis, lung cancer stages and malignancy, but not with age, sex or tumor size. Lung cancer cells with stably knocked down IGFBP-4 showed an inhibitory proliferation rate. The present study identified that IGFBP-4 was adversely associated with the prognosis of lung cancer patients. IGFBP-4 knockdown prohibited lung cancer cell growth. The present study provides a potential marker for lung cancer diagnosis and a possible target for lung cancer therapy.

Promoter methylation of APC and RAR-β genes as prognostic markers in non-small cell lung cancer (NSCLC)

Aberrant promoter hypermethylations of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine methylation status at APC and RAR-β promoters in primary NSCLC, and whether they have any relationship with survival. APC and RAR-β promoter methylation status were determined in 41 NSCLC patients using methylation specific PCR. APC promoter methylation was detectable in 9 (22.0%) tumor samples and 6 (14.6%) corresponding non-tumor samples (P=0.391). RAR-β promoter methylation was detectable in 13 (31.7%) tumor samples and 4 (9.8%) corresponding non-tumor samples (P=0.049) in the NSCLC patients. APC promoter methylation was found to be associated with T stage (P=0.046) and nodal status (P=0.019) in non-tumor samples, and with smoking (P=0.004) in tumor samples. RAR-β promoter methylation was found associated with age (P=0.031) in non-tumor samples and with primary tumor site in tumor samples. Patients with APC promoter methylation in tumor samples showed significantly longer survival than patients without it (Log-rank P=0.014). In a multivariate analysis of prognostic factors, APC methylation in tumor samples was an independent prognostic factor (P=0.012), as were N1 positive lymph node number (P=0.025) and N2 positive lymph node number (P=0.06). Our study shows that RAR-β methylation detected in lung tissue may be used as a predictive marker for NSCLC diagnosis and that APC methylation in tumor sample may be a useful marker for superior survival in NSCLC patients.

TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression.

Recent studies found that TIPE2 was involved in cancer development. However, little is known about TIPE2 in lung cancer. Our study aims to clarify the role of TIPE2 in lung carcinogenesis. We examined the expression of TIPE2 in lung squamous cancer (LSC), small cell lung cancer and lung adenocarcinoma (AdC) tissues and found that TIPE2 expression was lost in small cell lung cancer, compared with adjacent non-tumor tissues. Overexpression of TIPE2 significantly inhibited the growth of lung cancer cell H446 in vitro and even suppressed tumor formation in vivo. Flow cytometry analysis found TIPE2 overexpression promoted apoptosis of H446. In TIPE2 over-expression cells, caspase-3, caspase-9, and Bax were significantly up-regulated while Bcl-2 was down-regulated. Moreover, coincident results were shown by immunohistochemistry in tumors from nude mice. TIPE2 inhibited the phosphorylation of Akt, while promoting the phosphorylation of P38, but had no effect on IκBα and ERK pathway. Taken together, TIPE2 promoted lung cancer cell apoptosis through affecting apoptosis-related molecules caspase-3, caspase-9, Bcl-2 and Bax, possibly via regulating P38 and Akt pathways, indicating that TIPE2 might be a novel marker for lung cancer diagnosis and therapy.

Optimization of volatile markers of lung cancer to exclude interferences of non-malignant disease.

Breath analysis became promising for noninvasive diagnosis of cancer with sophisticated spectrometry technology introduced. This study aimed to select volatile markers for lung cancer detection, which exclude the influences from non-malignant lung diseases. 171 subjects who were divided into three groups: patients with LC, patients with PNMD and healthy controls were enrolled in our studies as training cohort. The volatile organic compounds (VOCs) in their breath samples were analyzed with solid-phase micro-extraction/gas chromatography/mass spectrometry (SPME-GCMS). Markers were selected by receiver operating characteristic (ROC) curves. After that, 78 subjects with high morbidity of LC were employed as validation cohort. Their breath samples were analyzed by thermal desorption instrument/gas chromatography/mass spectrometry (TD-GCMS). Through a series of comparisons among lung cancer patients, pulmonary non-malignant diseases patients, and healthy participants in training cohort, Nonane,5-(2-methyl-)propyl-; phenol,2,6-di-tert-butyl-,4-methyl-; dodecane,2,6,11-trimethyl-; hexadecanal and pentadecane,8-hexyl- were selected as markers for lung cancer diagnosis. Principal component analysis was employ to process data from validation cohort. As results, satisfied distinctions have been obtained with detection of these five selected markers, although the detection method is not identical with that used for training cohort. In conclusion, with optimization method described in this paper, breath test could be an effective method for diagnosis of lung cancer and avoid the interference of pulmonary non-malignant diseases.

Discovery of EST-SSRs in Lung Cancer: Tagged ESTs with SSRs Lead to Differential Amino Acid and Protein Expression Patterns in Cancerous Tissues

Tandem repeats are found in both coding and non-coding sequences of higher organisms. These sequences can be used in cancer genetics and diagnosis to unravel the genetic basis of tumor formation and progression. In this study, a possible relationship between SSR distributions and lung cancer was studied by comparative analysis of EST-SSRs in normal and lung cancerous tissues. While the EST-SSR distribution was similar between tumorous tissues, this distribution was different between normal and tumorous tissues. Trinucleotides tandem repeats were highly different; the number of trinucleotides in ESTs of lung cancer was 3 times higher than normal tissue. Significant negative correlation between normal and cancerous tissue showed that cancerous tissue generates different types of trinucleotides. GGC and CGC were the more frequent expressed trinucleotides in cancerous tissue, but these SSRs were not expressed in normal tissue. Similar to the EST level, the expression pattern of EST-SSRs-derived amino acids was significantly different between normal and cancerous tissues. Arg, Pro, Ser, Gly, and Lys were the most abundant amino acids in cancerous tissues, and Leu, Cys, Phe, and His were significantly more abundant in normal tissues than in cancerous tissues. Next, the putative functions of triplet SSR-containing genes were analyzed. In cancerous tissue, EST-SSRs produce different types of proteins. Chromodomain helicase DNA binding proteins were one of the major protein products of EST-SSRs in the cancerous library, while these proteins were not produced from EST-SSRs in normal tissue. For the first time, the findings of this study confirmed that EST-SSRs in normal lung tissues are different than in unhealthy tissues, and tagged ESTs with SSRs cause remarkable differences in amino acid and protein expression patterns in cancerous tissue. We suggest that EST-SSRs and EST-SSRs differentially expressed in cancerous tissue may be suitable candidate markers for lung cancer diagnosis and prediction.

EGFRandhTERTExpression as a Diagnostic Approach for Non-small Cell Lung Cancer in High Risk Groups

Objective:The early detection of NSCLC is of importance because it provides chances for better outcomes. The aim of the study was to explore the clinical utility of EGFR and hTERT mRNA expression as markers for diagnosis of NSCLC.Methods:EGFR and hTERT mRNA were quantified by quantative reverse transcription real time polymerase chain reaction in plasma of 45 non-small cell lung cancer (NSCLC) and 40 chronic obstructive pulmonary disease (COPD) patients, selected by certain spirometric characteristics that made them at high risk of developing lung cancer in future.Results:The gene expression level of each gene was calculated and given as a relative quantity—RQ. EGFR gene expression was found in all lung cancer patients. The mean level of expression was RQ = 29.39. hTERT mRNA could be detected in 88% of patients. The mean expression ratio in them was RQ = 17.31. Only 50% of the high risk patients turned to be positive for EGFR. The level of their expression was RQ = 2.09. The plasma levels of hTERT could be detected in 17 (42.5%) patients of the high risk COPD group. Their mean level of expression was RQ = 1.02. A statistically significant difference in EGFR and hTERT mRNA expression could be observed between the two groups of patients—p = 0.0001.Conclusion:EGFR and hTERT mRNA are potential markers for lung cancer diagnosis, whose clinical importance should be replicated in a larger cohort of patients.

Selective Expression of Calcium-Binding Protein S100A7 in Lung Cancer.

S100A7 is a member of S100 family and its overexpression has been previously associated with carcinogenesis of certain cancers. The aim of this study is to explore the expression of calcium-binding protein S100A7 in lung cancer. In the present study, RT-PCR, Western-blot and immunohistochemistry were used to analyze the different expression of S100A7 in lung cancer tissues and paired noncancerous lung tissues. The specific expression of S100A7 was found in squamous cell carcinomas and large cell lung carcinomas, whereas it was not detected in adenocarcinomas, small cell carcinomas, other cell types of lung cancer and normal lung tissues as well as paired noncancerous lung tissues. S100A7 was selectively expressed in squamous cell carcinomas and large cell lung carcinomas and may serve as a potential marker for lung cancer diagnosis.

Serum tumor markers for lung cancer diagnosis.

Progress has been made in research of lung cancer tumor markers in recent years,and these tumor markers have been used in clinical application. This study is to evaluate the regimens of six serum tumor markers in lung cancer diagnosis. The serum levels of the six tumor markers(NSE, pro-GRP, CYFRA21-1, SCC, p53 antibody and CA199) were detected in 80 healthy adults,170 patients with lung cancer and 80 patients with respiratory infection by ELISA. The levels of the six tumor markers in patients with lung cancer were remarkably higher than those in healthy adults and patients with respiratory infection(P <0.01).The levels of the NSE,pro-GRP in patients with small cell lung cancer were significantly higher than those in other subtypes of the lung cancer(P <0.01);The levels of the CYFRA21-1,SCC in patients with squamous carcinoma was remarkably higher than that in other subtypes of the lung cancer(P <0.01).The sensitivity of the NSE,pro-GRP in diagnosing small cell lung cancer was remarkably higher than that in other subtypes of the lung cancer(P <0.01); The sensitivity of the CYFRA21-1, SCC in diagnosing squamous carcinoma was remarkably higher than that in other subtypes of the lung cancer(P <0.01).The sensitivity of the tumor markers combinations in diagnosing lung cancer was remarkably higher than that of the single marker (P <0.01). Detection of the six tumor markers is helpful for diagnosis lung cancer. Combination of NSE and pro-GRP is more economic than other combinations in diagnosing small cell lung cancer; Combined CYFRA21-1,SCC is more economic than other combinations in diagnosing squamous carcinoma.

Selective expression of S100A7 in lung squamous cell carcinomas and large cell carcinomas but not in adenocarcinomas and small cell carcinomas

Background:S100A7 is a secreted protein and its overexpression has been previously associated with carcinogenesis of certain cancers. This study was undertaken to investigate the possibility that overexpression of S100A7 protein...

A Multiparametric Serum Kallikrein Panel for Diagnosis of Non–Small Cell Lung Carcinoma

Human tissue kallikreins are a family of 15 secreted serine proteases. We have previously shown that the expression of several tissue kallikreins is significantly altered at the transcriptional level in lung cancer. Here, we examined the clinical value of 11 members of the tissue kallikrein family as potential biomarkers for lung cancer diagnosis. Serum specimens from 51 patients with non-small cell lung cancer (NSCLC) and from 50 healthy volunteers were collected. Samples were analyzed for 11 kallikreins (KLK1, KLK4-8, and KLK10-14) by specific ELISA. Data were statistically compared and receiver operating characteristic curves were constructed for each kallikrein and for various combinations. Compared with sera from normal subjects, sera of patients with NSCLC had lower levels of KLK5, KLK7, KLK8, KLK10, and KLK12, and higher levels of KLK11, KLK13, and KLK14. Expression of KLK11 and KLK12 was positively correlated with stage. With the exception of KLK5, expression of kallikreins was independent of smoking status and gender. KLK11, KLK12, KLK13, and KLK14 were associated with higher risk of NSCLC as determined by univariate analysis and confirmed by multivariate analysis. The receiver operating characteristic curve of KLK4, KLK8, KLK10, KLK11, KLK12, KLK13, and KLK14 combined exhibited an area under the curve of 0.90 (95% confidence interval, 0.87-0.97). We propose a multiparametric panel of kallikrein markers for lung cancer diagnosis with relatively good accuracy. This model requires validation with a larger series and may be further improved by addition of other biomarkers.

Increased expression of high mobility group A proteins in lung cancer

High mobility group A (HMGA) proteins play an important role in the regulation of transcription, differentiation, and neoplastic transformation. In this work, the expression of HMGA 1 and 2 in 152 lung carcinomas of mainly non-small-cell histological type has been studied by immunohistochemistry in order to evaluate their feasibility as lung cancer markers. In 17 lung cancer cases, the related bronchial epithelial changes were also studied for HMGA1 and 2 expression. RNA expression of HMGA1a and b isoforms and of HMGA2 was determined by real-time semi-quantitative RT-PCR in 23 lung carcinomas. High expression of HMGA1 and HMGA2 at both mRNA and protein levels was detected in lung carcinomas, compared with normal lung tissue. Nuclear immunostaining for HMGA1 and 2 proteins also occurred in hyperplastic, metaplastic, and dysplastic bronchial epithelium. Increased nuclear expression of HMGA1 and 2 correlated with poor survival (for adenocarcinomas, HMGA1, p=0.006; HMGA2, p=0.05). While the expression of HMGA2 was significantly associated with cell proliferation (p=0.008), HMGA1 expression did not show any association with proliferation or apoptotic index. Sequencing of HMGA2 transcripts from tumours with very high expression showed a normal full-length transcript. As HMGA proteins were expressed in about 90% of lung carcinomas and their expression was inversely associated with survival, they may provide useful markers for lung cancer diagnosis and prognosis.

BJ-TSA-9, a Novel Human Tumor-Specific Gene, Has Potential as a Biomarker of Lung Cancer

Using bioinformatics, we have identified a novel tumorspecific gene BJ-TSA-9, which has been validated by Northern blot analysis and reverse transcriptionpolymerase chain reaction (RT-PCR). BJ-TSA-9 mRNA was expressed in 52.5% (21 of 40) of human lung cancer tissues and was especially higher in lung adenocarcinoma (68.8%). To explore the potential application of BJ-TSA-9 for the detection of circulating cancer cells in lung cancer patients, nested RT-PCR was performed. The overall positive detection rate was 34.3% (24 of 70) in peripheral blood mononuclear cells (PBMCs) of patients with various types of lung cancers and was 53.6% (15 of 28) in PBMCs of lung adenocarcinoma patients. In combination with the detection of two known marker genes SCC and LUNX, the detection rate was increased to 81.4%. A follow-up study was performed in 37 patients after surgical removal of tumor mass. Among nine patients with persistent detection of two to three tumor marker transcripts in PBMCs, six patients had recurrence/metastasis. In contrast, 28 patients with transient detection of one tumor marker or without detection of any tumor marker were all in remission. Thus, BJ-TSA-9 may serve as a marker for lung cancer diagnosis and as a marker, in combination with two other tumor markers, for the prediction of the recurrence and prognosis of lung cancer patients.

C-erbB-2 protein in serum of primary lung cancer patients

We determined c-erbB-2 protein level in serum of 86 primary lung cancer patients (78 non-small cell lung carcinomas (NSCLC), 3 small cell carcinomas, 5 not histologically defined) and in 61 controls. Aim of this study was to evaluate the clinical usefulness of c-erbB-2 as marker for lung cancer diagnosis. The protein was measured with a commercially available sandwich enzyme immunoassay. Mean levels of c-erbB-2 were 72.8±122.3 fmol/ml in lung cancers and 64.6±17.5 fmol/ml in controls ( P=0.2). No association was found between c-erbB-2 levels and histotype, tumor stage, sex and smoking habits. Among NSCLC, only four patients showed a c-erbB-2 concentration higher than the selected cut-off value of 99.6 fmol/ml. Subjects with levels higher than the 75th percentile in tumors (73 fmol/ml) had a shorter median survival than those with lower levels (6.3 months versus 10.0 months, P=0.003). Our results indicated that serum c-erbB-2 protein is not a reliable diagnostic marker. There is, however, a suggestion of a possible clinical usefulness in terms of survival prediction.