Biomedical subjects

Haruhiro Yukiue

Publications and source records attributed to Haruhiro Yukiue.

At least 19 recordsLinked to original sources

PubMed2007

EGFRvIII mutation in lung cancer correlates with increased EGFR copy number.

Overexpression of the epidermal growth factor receptor (EGFR) is caused by EGFR gene amplification and is sometimes associated with expression of a variant EGFR (deletion exon 2-7 or EGFRvIII). EGFRvIII mutation has oncogenic potential and is investigated as a potential therapeutic target. We genotyped the EGFRvIII mutation status in 252 surgically treated lung cancer cases. The presence or absence of EGFRvIII mutation was analyzed by real-time quantitative polymerase chain reaction (PCR) with mutation specific sensor and anchor probes. EGFR copy number was evaluated with PCR-based assay. EGFR mutation status at kinase domain has been examined and reported. EGFRvIII mutation was found on 8 of 252 patients. All patients were male, smokers, and 7 had squamous cell carcinoma. The mutation status was significantly correlated with pathological subtypes (squamous cell carcinoma vs. adenocarcinoma, p=0.0114). Sixty EGFR mutations at kinase domain exclusively existed with EGFRvIII mutations. EGFR gene copy number was significantly higher in EGFRvIII mutant (4.711+/-4.968) than in non-EGFRvIII mutant (2.284+/-1.224) (p=0.0001). EGFRvIII gene mutation might be one of the mechanisms of increased EGFR copy number. Further studies are needed to confirm the mechanisms of EGFRvIII mutations for possible anti-EGFR therapy for lung cancer.

Adenocarcinoma↗

PubMed2006

Mutation of epidermal growth factor receptor gene in adenosquamous carcinoma of the lung.

We have investigated 26 adenosquamous lung cancer tissues and found that four EGFR mutations were mainly in female and non-smoker lung cancer. However, EGFR mutation at kinase domain was exclusive with K-ras mutation. However, smoking and gender status could affect the occurrence of EGFR mutation. There was no difference in EGFR mutation status if analysis was performed in never smoker female subgroup.

Aged↗

PubMed2006

PIK3CA mutation status in Japanese lung cancer patients.

Somatic mutations of the PIK3CA (phosphatidylinostitol 3-kinase catalytic subunit) gene have been found in human cancer patients. Previous reports suggested that about 4% of lung cancers harbored PIK3CA gene mutations. However, the clinico-pathological background for PIK3CA gene mutations has not yet been investigated in lung cancer. We have genotyped the PIK3CA gene in Japanese lung cancer patients. The study included 235 lung cancer cases surgically removed in Nagoya City University Hospital. The two PIK3CA mutation hot spots (exon 9 and exon 20) were analyzed by real time polymerase chain reaction (PCR)-based assay. The data were confirmed by direct sequencing. In exon 9, somatic mutation was found in eight patients (3.4%). The mutation included three E542K (G1624A), three E545K (G1633A), one E542Q (G1624C), and one Q546K (C1636A). However, in exon 20, there was no mutation in our lung cancer patients. PIK3CA mutations were not correlated with gender (women versus men, p=0.4162), age (< or =60 versus >60, p=0.8027), or smoking status of the lung cancers (never versus smoker, p=0.5666). PIK3CA mutation incidence was significantly lower in adenocarcinoma (2/135, 1.5%) than in squamous cell carcinoma (5/77, 6.5%, p=0.0495). Among eight patients with a PIK3CA mutation, three patients also harbored an EGFR somatic mutation. PIK3CA gene mutations were rare in lung cancer; rarer in adenocarcinoma. Further functional analyses of the PIK3CA mutations are warranted to study if they could be the target of therapy for the lung cancer.

Adenocarcinoma↗

PubMed2006

L858R EGFR mutation status correlated with clinico-pathological features of Japanese lung cancer.

Somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in about 25-40% of Japanese lung cancer patients. These mutations are associated with clinical and radiographic responses to EGFR tyrosine kinase inhibitors. Most common mutation are arginine for leucine substitution at amino acid 858 (L858R) and exon 19 deletions, especially deletion type 1 mutation. We investigated these EGFR mutation statuses in 575 surgically treated non-small cell lung cancer (NSCLC) cases. Three-hundred and sixty-two adenocarcinoma cases were included. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis (TaqMan assay; n=386, and LightCycler assay; n=98) and sequences (n=91). EGFR mutations (CTG; CGG; L858R) were found from 63 of 575 lung cancer patients. We also detected the deletion 1a type mutations (2235-2249 del GGAATTAAGAGAAGC) from 39 patients and deletion 1b type mutations (2236-2250 del GAATTAAGAGAAGCA) from 15 patients in exon 19. These mutation statuses were significantly correlated with gender, smoking status (never smoker versus smoker), and pathological subtypes (adenocarcinoma versus non-adenocarcinoma). L858R mutation (p<0.0001), but not deletion 1 type mutation (p=0.0665), was correlated with differentiation status (well versus moderately or poorly) of lung cancers. L858R mutation ratio was significantly higher in non-smoker (p=0.0496) and adenocaicinoma (p=0.0136) when compared to deletion 1 type mutations. The EGFR mutation status, especially L858R mutation might be correlated with the clinico-pathological features related to good response to gefitinib, such as gender, smoking history, and pathological subtypes of Japanese lung cancers.

Adenocarcinoma↗

PubMed2006

Expression and mutation statuses of epidermal growth factor receptor in thymic epithelial tumors.

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations have been reported to correlate with the sensitivity to the tyrosine kinase inhibitor treatment for advanced lung cancers. Since several reports have shown that invasive thymoma overexpress the EGFR protein, we examined the EGFR expression and mutation statuses in thymoma and thymic carcinoma tissues. METHODS: EGFR mutation statuses from 99 thymic epithelial tumor samples were evaluated by a rapid and sensitive TaqMan assay using Applied Biosysytems 7500 real-time PCR system. Probes were designed according to the 13 different EGFR mutations reported previously in lung cancers. A total of 38 thymoma samples were directly sequenced for the EGFR gene. Protein expressions were evaluated for 56 thymic epithelial tumors by immunohistochemistry. RESULTS: EGFR gene mutations were not detected in any of the thymoma and thymic cancer samples using TaqMan PCR assay. Of the 38 samples 3 showed a heterozygous silent mutation without changes in the protein, a G to A transition at the nucleotide 2361 in exon 18. EGFR expression was significantly higher in invasive thymomas (stages III-IV, 15/19 were positive) than in early stage thymomas (stages I-II, 7/33 were positive) (P < 0.0001). All four carcinomas and all seven B3 thymomas showed EGFR positive staining. CONCLUSIONS: Although EGFR mutation at the tyrosine kinase domain is unlikely to be a therapeutic target for thymoma, the information about EGFR expression would contribute to the further identification of the therapeutic target for advanced thymomas.

Adult↗

PubMed2006

Preoperative steroid pulse therapy for invasive thymoma: clinical experience and mechanism of action.

BACKGROUND: Glucocorticoid was used in thymomas. The purpose of the study was to evaluate the efficacy of intravenous high-dose glucocorticoid (steroid pulse) therapy in patients with previously untreated advanced thymoma. Causes were also sought for a possible underlying mechanism of the effect of steroid on thymoma. METHODS: Seventeen patients with invasive thymoma who had not received previous chemotherapy or radiation therapy were enrolled in the study. All cases were treated with 2 courses of glucocorticoid therapy before surgery. Tumor response was assessed by computed tomography (CT) scan 1 week after the steroid pulse therapy. Lymphocytes associated with thymoma were analyzed for their CD4/CD8 phenotype and glucocorticoid receptor (GR). TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining was used to analyze the apoptotic lymphocytes and epithelial cells. RESULTS: The overall response rate to the steroid pulse therapy was 47.1% (8 of 17). The reduction in tumor size was most prominent in type B1 thymomas; there were significant differences between type AB and type B1 thymomas (P = .0234) and type B1 and type B3 thymomas (P = .0068). The reduction in tumor size was accompanied with a marked reduction in the CD4+8+ double-positive immature thymocytes that expressed higher levels of glucocorticoid receptor. Apoptotic changes were observed in both neoplastic epithelial cell and lymphocyte components after glucocorticoid therapy. CONCLUSIONS: The efficiency of preoperative steroid pulse therapy in type B1 thymoma was most prominent, which is probably related to the specific effect on GR-rich CD4+8+ double-positive immature lymphocytes, which are abundant in this type of thymoma.

Adult↗

PubMed2006

Epidermal growth factor receptor gene mutation defines distinct subsets among small adenocarcinomas of the lung.

Epidermal growth factor receptor (EGFR) gene mutations are frequently detected in lung cancer, especially in adenocarcinoma, in females, and non-smoking patients. EGFR mutations are closely associated with clinical response to EGFR tyrosine kinase inhibitor. Bronchioloalveolar carcinoma (BAC) appearance is a good predictor of response to this agent. Noguchi et al. subdivided small peripheral adenocarcinoma of the lung into two groups. One group was characterized with tumor cell growth replacing the normal alveolar cells with varying degree of fibrosis (types A-C), and the other shows non-replacing and destructive growth (types D-F). Using probes for the 13 mutations which have been previously described, we have genotyped the EGFR gene status in surgically resected atypical adenomatous hyperplasias (AAH) and small peripheral adenocarcinomas up to 2 cm in diameter using TaqMan PCR assay. In 95 small-sized adenocarcinomas, the EGFR mutations were detected in 37 patients (38.9%), and no mutations were found in five AAHs. In small peripheral adenocarcinomas, EGFR mutations were found 47.1% of types A, B, or C adenocarcinomas; it was less frequent (16%) in Noguchi's types D, E or F adenocarcinomas. These results suggest that type D, F adenocarcinomas are not derived from the less malignant types A-C adenocarcinomas; rather, they have arisen de novo by distinct mechanisms. Although types A and B adenocarcinomas are almost 100% cured by surgery, some type C adenocarcinoma show lymph node metastasis and relapse. EGFR mutation analysis may help identify patients who will respond to treatment with tyrosine kinase inhibitors, e.g., gefitinib.

Adenocarcinoma↗

PubMed2006

A correlation between EGFR gene mutation status and bronchioloalveolar carcinoma features in Japanese patients with adenocarcinoma.

BACKGROUND: The presence of epidermal growth factor receptor (EGFR) mutations in gefitinib-naive lung cancer patients has been reported to be higher in females, in non-smokers, in Japanese, and in adenocarcinoma patients, especially in bronchioloalveolar carcinoma (BAC). To further investigate the prevalence of EGFR mutations in relation to pathological factors, we evaluated EGFR mutations in series of Japanese adenocarcinoma patients who had never been treated with gefitinib. METHODS: In the previous studies, we examined mutation status in the tyrosine kinase domain of EGFR, exon18 through exon21, in 112 primary lung adenocarcinoma samples. Using these data, adenocarcinomas were histologically classified according to the presence or absence of bronchioloalveolar components. RESULTS: Among 112 patients, 48 had adenocarcinoma with BAC components. Those with adenocarcinomas with BAC components had higher frequency of EGFR mutation (28/48, 58%) than those with non-BAC adenocarcinoma (24/64, 37%, P = 0.036). Male patients had the same trend; 12/23 (52%) male patients with adenocarcinoma with BAC components and 10/47 (21%) of those with non-BAC adenocarcinoma had EGFR mutation (P = 0.0135) but there was no correlation between the EGFR mutation status and with/without BAC components in 42 female patients (P = 0.30). Among 11 male non-smokers, patients with adenocarcinoma with BAC components had a tendency to have EGFR mutation more frequently than those with non-BAC adenocarcinoma (P = 0.061). In clear contrast, the frequency of EGFR mutation did not differ significantly between male smoker patients with adenocarcinoma with BAC components and those with non-BAC. Among patients with adenocarcinoma with BAC components, those with adenocarcinoma with EGFR gene mutation had a significantly better 5 year survival than those with adenocarcinoma with wild-type (85.7 versus 46.0%, P = 0.0017). CONCLUSIONS: Adenocarcinomas with BAC components in male non-smokers seem to predict the presence of EGFR mutation. Half of female adenocarcinoma patients with EGFR mutation exhibit adenocarcinomas with non-BAC suggesting a different behavior from those in males. The prognosis of patients with adenocarcinoma with BAC components with EGFR gene mutation is predicted to be better than that of patients with adenocarcinoma with BAC components with wild-type EGFR gene.

Adenocarcinoma↗

PubMed2006

Decreased fragile histidine triad gene messenger RNA expression in lung cancer.

BACKGROUND: The fragile histidine triad (FHIT) gene is located at 3p14.2, a region frequently lost in various tumor types. Lack of FHIT expression has been found to occur frequently in multiple tumor types including lung cancer. We have investigated FHIT messenger RNA (mRNA) levels and other clinicopathologic data, including FHIT and p21 expression in lung cancer. PATIENTS AND METHODS: The study included 97 lung cancer cases. The FHIT mRNA levels were quantified by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) using LightCycler. RESULTS: The FHIT/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were decreased in tumor tissues from lung cancer (13.844 +/- 33.047) compared with adjacent nonmalignant lung tissues (195.763 +/- 678.469; P < 0.0001). No significant difference in FHIT/GAPDH mRNA levels was found among age, T status, or lymph node metastasis. The FHIT/GAPDH mRNA level was less in squamous cell carcinoma (0.144 +/- 0.246), a smoking-related cancer, than in adenocarcinoma (0.72 +/- 1.321; P = 0.0355). FHIT/GAPDH mRNA levels were correlated with FHIT protein (P = 0.0139) and p21 protein (P = 0.0484) expression by immunohistochemistry. The prognosis for patients with lung cancer with low FHIT/GAPDH levels (< 0.26; n = 57) was significantly worse than in the patients with high FHIT/GAPDH levels (> 0.26; n = 40; log-rank test, P = 0.0404). CONCLUSION: Using the LightCycler RT-PCR assay, decreased FHIT gene expression might occur early and play an important role in lung tumorigenesis and also correlate with the prognosis of lung cancer. However, further studies are needed to confirm the impact of FHIT in the biologic behavior of the tumor.

Acid Anhydride Hydrolases↗

PubMed2006

Decreased kallikrein 11 messenger RNA expression in lung cancer.

BACKGROUND: Human kallikrein 11 (hK11) is a putative serine protease of the human kallikrein gene family. A recently developed method for measuring hK11 suggested that the hK11 level was an indicator of favorable prognosis in patients with ovarian cancer. We have investigated hK11 messenger RNA (mRNA) levels in lung cancer. PATIENTS AND METHODS: This study included 64 lung cancer cases. The hK11 mRNA levels were quantified by real-time reverse-transcriptase polymerase chain reaction using LightCycler. RESULTS: The hK11 mRNA levels were lower in tumor tissues from lung cancer (1.88 +/- 6.314) compared with adjacent nonmalignant lung tissues (8.271 +/- 9.002; n = 45; P = 0.0001). No significant difference was found among sex, age, clinical stages, tumor status, and lymph node metastasis. The hK11 mRNA levels were lower in moderately or poorly differentiated adenocarcinoma lung cancer (0.452 +/- 1.614) compared with well-differentiated adenocarcinoma lung cancer (1.728 +/- 2.829; P = 0.0281). The group with low hK11/gylceraldehyde 3-phosphate dehydrogenase levels (< 0.6) had a significantly worse prognosis compared with the group with high hK11/gylceraldehyde 3-phosphate dehydrogenase levels (> 0.6; log-rank test, P = 0.0131; Breslow-Gehan-Wilcoxon test, P = 0.0172). CONCLUSION: Cox proportional hazard regression model (multivariate analysis) indicated that pathologic stages (P = 0.0443) and low hK11 expression levels (P = 0.0469) were the prognostic factors of lung cancers. However, additional studies and a longer follow-up are needed to confirm the impact of hK11 on the biologic behavior of the tumor.

Adenocarcinoma↗

PubMed2006

Evaluation of the epidermal growth factor receptor gene mutation and copy number in non-small cell lung cancer with gefitinib therapy.

Several studies have suggested that epidermal growth factor receptor (EGFR) gene mutation, EGFR gene amplification, and some other biomarkers may be predictors of gefitinib sensitivity. We analyzed EGFR mutation and EGFR copy number in 22 gefitinib-treated non-small cell lung cancer (NSCLC) cases and their relation to the survival of patients. We also studied 143 gefitinib-naïve Japanese NSCLC cases. The erbB2 copy number was also studied in 59 gefitinib-naïve NSCLC cases. In gefitinib-treated patients, the presence of EGFR mutation was associated with a higher response rate to gefitinib and a longer overall survival, but the increased EGFR gene copy number was not. In gefitinib-naïve cases, EGFR mutation but not EGFR gene copy number was significantly correlated with gender, pathological subtypes, and smoking status. The erbB2 copy number was not significantly correlated with the EGFR mutation or EGFR copy number in 59 cases. In conclusion, EGFR mutation was a better predictor of clinical outcome in gefitinib-treated patients than the EGFR gene copy number.

Adenocarcinoma↗

PubMed2005

Uncommon V599E BRAF mutations in Japanese patients with lung cancer.

BACKGROUND: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene and Braf gene were found in patients with lung cancer. These mutations might be correlated with a clinical response to molecular target therapy. Although a few Caucasian lung cancer patients harbored BRAF mutations, there have been no reports about the BRAF mutation in Japanese patients with lung cancer. MATERIALS AND METHODS: We investigated BRAF mutations in Japanese lung cancer patients. The study included 129 surgically removed lung cancer cases from Nagoya City University Hospital. Braf, EGFR, and erbB2 mutations also were analyzed by reverse transcript polymerase chain reaction (RT-PCR) and direct sequencing. RESULTS: In exon 15, one BRAF mutation (1796 thymine to adenine; V599E) was found in nonsmoking woman with well-differentiated adenocarcinoma. We detected the 43 EGFR mutations, including 19 at exon 19 and 20 at exon 21 from the 129 patients analyzed (33.3%). We also detected one erbB2 mutation from 76 patients analyzed. All these mutations existed exclusively. CONCLUSIONS: V599E BRAF mutation was uncommon in Japanese lung cancer. All three genes mutations were predominantly found in female nonsmoking subjects with adenocarcinomas. However, completely exclusive mutation status would help us to choose custom-made molecular target therapy for the lung cancer.

Adenocarcinoma↗

PubMed2004

Elevated serum epidermal growth factor receptor level in stage IV thymoma.

Using the enzyme immunoassay for epidermal growth factor receptor (EGFR), we investigated whether serum EGFR levels could be used as a predictor of the development and extension of thymoma. Serum samples were collected from 31 patients with thymoma and 16 patients with nonmalignant thoracic disease before clinical treatment. There was no difference between the serum EGFR levels of the patients with thymoma and the nonmalignant controls, being 49.1 +/- 136.3 and 22.6 +/- 7.3 fm/ml, respectively ( P = 0.11). However, patients with stage IV thymoma had significantly higher EGFR levels than those with stage I or stage II thymoma, the respective values being 127.8 +/- 243.9, 10.9 +/- 9.2 ( P = 0.02), and 19.7 +/- 10.6 ( P = 0.0433) fm/ml. The serum EGFR levels were similar in the pathological subtypes. These findings suggest that serum EGFR levels may serve as a marker that could be used as a diagnostic indicator of the invasion of thymoma.

Biomarkers, Tumor↗

PubMed2004

Arg and DAP3 expression was correlated with human thymoma stage.

Thymoma is one of the most common solid tumors in the mediastinum. As there is no typical cell line for human thymoma, the development and use of molecular-based therapy for thymoma will require detailed molecular genetic analysis of patients' tissues. The recent reports showed that the gain of chromosome 1q regions was frequent in thymoma. We investigated the use of oligonucleotide arrays to monitor in vivo gene expression levels at chromosome 1q regions in the early- (stage I or II) and late-stage (stage IVa) thymoma tissues from patients. These in vivo gene expression profiles were verified by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) using LightCycler for 36 thymoma patients. Using both the methods, candidate genes were come up. These are Arg tyrosine kinase and death-associated protein 3 (DAP3), which are known as ionizing radiation resistance conferring proteins. The Arg/GAPDH mRNA level in stage IV thymoma (90.716 +/- 177.851) was significantly higher than in stage I thymoma (10.335 +/- 25.744, P = 0.0465). The DAP3/GAPDH mRNA level in stage IV thymoma (17.424 +/- 20.649) was significantly higher than in stage I thymoma (5.184 +/- 3.878, P = 0.0305). DAP3 expression was also correlated with the WHO classification. The combined use of oligonucleotide microarray and real-time RT-PCR analyses provided a candidate molecular marker surrounding the development and progression of thymoma correlated with chromosome 1q.

Apoptosis Regulatory Proteins↗

PubMed2004

Decreased Hrad6B expression in lung cancer.

Human homologues of yeast Rad 6 (Hrad6B) encode ubiquitin-conjugating enzymes and complement the DNA repair and UV mutagenesis defects of Saccharomyces cerevisiae rad6 mutant. There is a larger subgroup with reduced DNA repair capacity that is likely to be at increased cancer risk. The authors investigated Hrad6B expression in lung cancer. An attempt was made to determine the influence of Hrad6B expression on clinicopathological features for patients with lung cancer who had undergone surgery. Expression of Hrad6B messenger RNA was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 110 lung carcinomas and adjacent histological non-malignant lung samples from patients for whom follow-up data were available using LightCycler. The Hrad6B/glyceraldehydes-3-phosphate dehydrogenase (GAPDH) mRNA expression was significantly decreased in the lung cancer tissue (4.078+/-5.674) as compared with the non-malignant lung tissue (10.495+/-12.976, p<0.001). There was no relationship between Hrad6B/GAPDH expression and age, clinical stages, T-status, N-status, and pathological subtypes in lung cancer tissues. Hrad6B/GAPDH mRNA levels in males (3.521+/-4.280) and in females (6.420+/-8.167) were significantly different (p=0.0443) in lung cancer tissues, but not in non-malignant lung tissues. Heavy smokers had a slight non-significant tendency (p=0.0857) towards lower Hrad6B/GAPDH mRNA levels (3.453+/-4.743) in their lung cancer tissues as compared with light or non-smokers. Thus decreased Hrad6B mRNA expression might be a biomarker for decreased DNA repair capacity and the dysfunction of Hrad6B might play a role in the tobacco-related oncogenesis of lung cancer.

Aged↗

PubMed2003

Elevated serum epidermal growth factor receptor level is correlated with lymph node metastasis in lung cancer.

BACKGROUND: Using an enzyme immunoassay for epidermal growth factor receptor (EGFR), we investigated whether serum EGFR levels could be used as predictors of the development and extent of lung cancer. METHODS: The study included 106 lung cancer patients and 16 patients with nonmalignant thoracic disease. Serum samples were collected before clinical treatment. RESULTS: There was no difference between serum EGFR levels in patients with lung cancer (21.275 +/- 22.035 fm/ml) in comparison with those in nonmalignant-disease controls (22.630 +/- 7.330 fm/ml; P = 0.8083). However, lung cancer patients with lymph node metastasis (23.515 +/- 20.065 fm/ml) had significantly higher EGFR levels compared with those in patients without lymph node metastasis (16.390 +/- 10.970 fm/ml; P = 0.0228). The serum EGFR levels were similar in samples from lung cancer patients with various pathological subtypes. There was no difference in the prognosis between the lung cancer group with normal EGFR levels (<850 ng/ml) and the group with elevated EGFR levels (>850 ng/ml). CONCLUSION: Serum EGFR levels may serve as a marker that can be used as an indicator of lymph node metastasis in lung cancer. However, there was no difference between levels in patients with lung cancer and those in nonmalignant-disease controls, indicating that the measurement of serum EGFR levels was of limited value in the detection of lung cancer.

Aged↗

PubMed2003

Hrad17 expression in thymoma.

OBJECTIVES: We used palindromic polymerase chain reaction-driven complementary deoxyribonucleic acid differential display to identify and isolate a gene, the human homolog of the Schizosaccharomyces pombe checkpoint gene rad17 (Hrad17), from colon cancer tissue. The loss of checkpoint control in mammalian cells results in genomic instability, leading to the amplification, rearrangement, or loss of chromosomes--events associated with tumor progression. We hypothesized that the Hrad17 may be expressed in thymoma, especially in invasive thymoma. We attempted to determine the influence of Hrad17 expression on clinicopathological features for patients with thymoma who had undergone surgery. METHODS: Expression of Hrad17 messenger ribonucleic acid (RNA) was evaluated by reverse transcription-polymerase chain reaction using a LightCycler in 38 thymomas and 10 adjacent histologically normal thymus samples from patients for whom follow-up data was available. RESULTS: Hrad17 transcripts were detected in all 38 tumor samples (8.789 +/- 7.337) at levels significantly higher than those in normal thymus samples (1.908 +/- 2.267, p < 0.0001). No relationship was seen between Hrad17 gene expression and age, gender, or pathological thymoma subtypes. Hrad17 mRNA expression in invasive thymomas (stage II-IV, 10.067 +/- 5.293) was significantly higher than that in stage I thymomas (5.193 +/- 4.485, p = 0.0168). Immunohistochemistry showed that Hrad17 protein was highly expressed in invasive thymoma tumor tissue but not within the normal thymus tissue. CONCLUSIONS: Hrad17 was highly expressed in invasive thymoma.

Cell Cycle Proteins↗

PubMed2003

Cten mRNA expression was correlated with tumor progression in lung cancers.

Cten is a recently isolated gene, which has homology with tensin suggesting that it is a focal adhesion molecule. Tensin family proteins play an important role in cell motility. We attempted to determine the influence of cten expression on clinicopathological features in patients with lung cancer who had undergone surgery. Expression of cten messenger RNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in 89 lung carcinomas and adjacent histological normal lung samples using LightCycler. Cten/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression was not significantly different between lung cancer tissue (1.479+/-2.060) and normal lung tissue (1.528+/-1.592, P=0.8267). There was no relationship between cten/GAPDH expression and age, gender or N-status. However, tumor/normal ratio (T/N ratio) of cten/GAPDH expression was significantly higher in stage II-IV lung cancer (3.113+/-6.493) when compared with stage I lung cancer (1.237+/-1.820, P=0.0316). T/N ratio of cten/GAPDH expression was significantly higher in T4 lung cancer (4.612+/-9.726) when compared with T1 lung cancer (0.896+/-0.860, P=0.0252), and T2 lung cancer (1.636+/-2.066, P=0.0470), respectively. Thus cten/GAPDH mRNA expression has been correlated with evidence of tumor progression in terms of T and overall stage of lung cancer. Alternatively, cell motility or migration might play a role in progression of lung cancer.

Carcinoma, Non-Small-Cell Lung↗