Masahiro Kaji

Prognostic significance of [18F]fluorodeoxyglucose uptake on positron emission tomography in patients with pathologic stage I lung adenocarcinoma

[18F]Fluoro‐2‐deoxyglucose uptake on positron emission tomography (FDG‐PET) has been frequently used for diagnosis and staging of lung cancer. The prognostic significance of FDG uptake on PET was evaluated in patients with pathologic Stage I lung adenocarcinoma (tumor stages were based on the TNM classification of the International Union Against Cancer).

Expression of the MTA1 mRNA in advanced lung cancer

The MTA1 gene is a recently identified metastasis-associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in non-small cell lung cancer (NSCLC). Expression of MTA1 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 74 non-small cell lung carcinoma samples using LightCycler. The data was analyzed in reference to clinicopathological data. There was no relationship between MTA1 gene expression and age and gender. MTA1/GAPDH mRNA level in stage II-IV NSCLC (3.465+/-3.675) was significantly higher than the level in stage I NSCLC (1.614+/-2.434, P=0.0153). MTA1/GAPDH mRNA levels in T4 NSCLC (4.377+/-4.169) was significantly higher than the level in T1 NSCLC (1.966+/-2.148, P=0.0351) and in T2 NSCLC (2.048+/-1.899, P=0.0269), respectively. MTA1/GAPDH mRNA level in NSCLC with lymph node metastasis (4.242+/-3.758) was significantly higher in NSCLC without lymph node metastasis (P=0.0169). Our results show that the expression of the MTA1 gene is closely related to invasiveness and metastasis in NSCLC. The gene MTA1 could thus potentially provide information on the mechanism of cancer invasion and metastasis.

Decreased perioxisome proliferator-activated receptor gamma gene expression was correlated with poor prognosis in patients with lung cancer

Activation of the nuclear hormone receptor perioxisome proliferator-activated receptor gamma (PPARgamma) inhibits cell growth and induces apoptosis in several human cancers. We have hypothesized that PPARgamma mRNA levels could be predictors of the differentiation and survival of lung cancer. The study included 77 lung cancer cases. The mRNA levels were quantified by real time reverse transcription-polymerase chain reaction (RT-PCR) using LightCycler. The PPARgamma mRNA levels were decreased in tumor tissues from lung cancer (0.579 +/- 1.255) compared to the normal adjacent lung tissues (4.191 +/- 2.868) (P = 0.0001). No significant difference in PPARgamma mRNA levels was found among gender, age, and pathological subtype. The PPARgamma mRNA levels were higher in tumor tissues from higher differentiated lung cancer. The NSCLC patients with low PPARgamma mRNA expression (< 0.5) had significantly worse survival than the patients without low PPARgamma mRNA levels (P = 0.0438, Breslow-Gehan-Wilcoxon test; P = 0.0168, Coxs proportional-Hazards regression model). Thus, PPARgamma mRNA levels may serve as a prognostic marker in lung cancer. Using the LightCycler RT-PCR assay, the determination of PPARgamma mRNA levels might provide a potential marker for treatment of lung cancer by PPARgamma agonist. However, further studies and a longer follow up are needed to confirm the impact of PPARgamma in the biological behavior of the tumor.

Serum level of the periostin, a homologue of an insect cell adhesion molecule, in thymoma patients

Periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule. Periostin has a typical signal peptide at the N-terminal end suggesting it is a secreted protein. Recently, we developed a novel sandwich chemiluminescence assay to determine serum concentrations of periostin. We investigated the serum periostin level in thymoma patients, and attempted to determine the correlation between serum periostin level and clinicopathological factors of thymoma patients who had undergone surgery between January 1994 and July 1996. Serum periostin levels were not significantly different between the thymoma patients (1264.4+/-122.9 ng/ml) and the normal control (962.0+/-118.6 ng/ml) (P=0.0877). There was no relationship between serum periostin level and age, gender or pathological subtype. However the serum periostin level of stage IV patients (1497.0+/-285.8 ng/ml) was significantly higher than normal control (P=0.0460). These data suggest that serum periostin level may indicate tumor invasion and progression of thymoma.

Elevated serum vascular endothelial growth factor and basic fibroblast growth factor levels in patients with thymic epithelial neoplasms.

Abstract Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors, among which vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are considered to exert potent angiogenic activity. In this study, we investigated whether serum VEGF and bFGF levels could be predictors of the development and extension of thymic epithelial neoplasms. The subjects of this study were 37 patients with thymoma, 6 with thymic carcinoma, and 23 healthy volunteers. Serum samples were collected before clinical treatment. Serum VEGF levels were significantly (P < 0.05) elevated in the patients with thymic carcinoma (1 080 ± 1 185 pg/ml) compared with those in the healthy volunteers (407 ± 589 pg/ml). Serum bFGF levels were also significantly (P < 0.05) elevated in the patients with thymic carcinoma (2 740 ± 631 pg/ml) compared with those in the healthy volunteers (1 728 ± 1 192 pg/ml). However, the serum VEGF and bFGF levels did not significantly differ between the patients with thymoma and the healthy volunteers. Serum VEGF and bFGF levels did not significantly differ according to the stage and pathological subtype of thymoma. Moreover, there was no correlation between the serum levels of VEGF and those of bFGF. Thus, while serum VEGF and bFGF levels may serve as markers for thymic epithelial tumors, it is unlikely that circulating VEGF and bFGF could be used as markers for assessing the progression of thymoma tumors.

Expression of the MTA1 mRNA in thymoma patients

The MTA1 gene is a recently identified metastasis-associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in thymoma. Expression of MTA1 mRNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 30 thymoma samples using LightCycler. The data was analyzed in reference to clinicopathological data. There was no relationship between MTA1 gene expression and age and gender. MTA1/GAPDH mRNA level in stage IV thymoma (6.431+/-3.404) was significantly higher than the level in stage I thymoma (2.592+/-1.902, P=0.0081). There was a tendency towards higher MTA1/GAPDH mRNA level in stage IV thymoma when compared to stage II thymoma (3.746+/-3.292, P=0.072). Thus our results show that the expression of the MTA1 gene is closely related to invasiveness in thymoma. The gene MTA1 could potentially provide information on the mechanism of tumor invasion and metastasis.

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.

18F-fluorodeoxyglucose and 11C-acetate positron emission tomography are useful modalities for diagnosing the histologic type of thymoma

The objective of this study was to clarify the usefulness of positron emission tomography (PET) using18F‐fluorodeoxyglucose (FDG) and carbon 11‐labeled acetate (AC) for predicting the histologic types and tumor invasiveness of thymoma in a multicenter study.

Expression of the antiapoptosis gene, AAC-11, as a prognosis marker in non-small cell lung cancer

Inhibition of programmed cell death (apoptosis) is associated with increased tumor aggressiveness. We hypothesized that a novel apoptosis inhibitor gene, antiapoptosis clone 11 (AAC-11), may be expressed in tumors of patients with non-small cell lung cancer (NSCLC) and affect their clinical outcome. Expression of AAC-11 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 94 non-small cell lung carcinomas and adjacent histologically normal lung samples. The data was analyzed in reference to clinicopathological and survival data. AAC-11 transcripts were detected in 12 (12.7%) of the tumor samples, although five of paired normal lung samples showed very weak expression. There was no relationship between AAC-11 gene expression and age, gender, N or T-status. AAC-11 was preferentially expressed in squamous cell carcinoma (26.9% of squamous cell carcinoma vs. 7% of adenocarcinoma). The NSCLC patients with AAC-11 expression had significantly poor survival than the patients without AAC-11 expression (P=0.0360). Although the AAC-11 gene was not expressed in a majority of NSCLC tumors, we suggest that AAC-11 may predict poor survival.

Expression of the sensitive to apoptosis gene, SAG, as a prognostic marker in nonsmall cell lung cancer.

Inhibition of programmed cell death (apoptosis) is associated with increased tumor aggressiveness. We hypothesized that a novel sensitive to apoptosis gene, SAG, may be expressed in tumors of patients with nonsmall cell lung cancer (NSCLC) and may affect their clinical outcome. Expression of SAG messenger RNA was evaluated by reverse transcription polymerase chain reaction in 80 nonsmall cell lung carcinomas and 65 adjacent histologic nonmalignant lung samples using a LightCycler. The data were analyzed in reference to clinicopathologic data and survival. The SAG/GAPDH mRNA level in 80 NSCLC was 2.337 ± 1.972. Of 65 paired NSCLC and nonmalignant lung samples, SAG/GAPDH mRNA levels were 2.313 ± 2.064 and 1.696 ± 1.910, respectively. The SAG mRNA level was significantly higher in NSCLC compared with nonmalignant lung tissue (p = 0.0169). There was no relationship between SAG gene expression and age, gender, T‐ or N‐status or clinical stages. The NSCLC patients with high SAG/GAPDH expression (>1.8) had significantly poorer survival than the patients with low SAG/GAPDH expression (<1.8, p = 0.0227). Thus we suggest that SAG gene expression in NSCLC may be a useful prognostic marker.