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1.
Lung Cancer ; 81(3): 475-479, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23891508

ABSTRACT

BACKGROUND: Regulatory T cells (Tregs) are potent immunosuppressive cells that play a crucial role in tumor immune escape. The purpose of the present study was to evaluate the prognostic significance of the frequency of CD4+CD25+Foxp3+ Tregs in the regional lymph node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL) in patients who underwent surgical resection of non-small cell lung cancer (NSCLC). METHODS: The RLNL and PBL in 158 NSCLC patients who underwent complete surgical resection were collected at the time of surgery. The proportions of CD4+CD25+Foxp3+ cells in the RLNL and PBL were determined by flow cytometry. RESULTS: The average proportions of Tregs in the RLNL and PBL were 1.28% and 0.76%, respectively. The proportion of Tregs in the RLNL was significantly higher than that in the PBL (p < 0.0001). The 5-year overall survival rates of the patients according to the proportion of Tregs in the RLNL were 84.4% and 63.5% in the lower and higher groups, respectively. A significant difference was observed in the survival rate between the higher and lower groups (p = 0.0056). Among the patients with stage I disease, the 5-year survival rate (91.4%) was significantly higher in patients with the lower proportion of Tregs in RLNL that in the higher group (72.1%) (p = 0.0147). CONCLUSIONS: The higher proportion of Tregs in the RLNL was a significant unfavorable prognostic factor, even in patients with node-negative NSCLC. The information about the proportion of Tregs in the RLNL might improve the discriminatory power for assessing the risk of the recurrence of NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/immunology , Lung Neoplasms/mortality , Lymph Nodes/immunology , T-Lymphocytes, Regulatory/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Immunophenotyping , Lung Neoplasms/pathology , Lymph Nodes/metabolism , Male , Middle Aged , Neoplasm Staging , Phenotype , Prognosis , T-Lymphocytes, Regulatory/metabolism , Young Adult
2.
Anticancer Res ; 33(5): 2123-8, 2013 May.
Article in English | MEDLINE | ID: mdl-23645764

ABSTRACT

AIM: The purpose of this study was to investigate the clinical significance of expression of cancer/testis (CT) antigen and down-regulation of HLA class-I in patients with stage I non-small cell lung cancer (NSCLC), which underwent complete surgical resection. PATIENTS AND METHODS: The expression of HLA class-I molecules was evaluated in 136 resected NSCLC specimens by immunohistochemistry. The results were scored as the percentage of stained tumor cells and categorized into two groups: 0-79%, reduced expression; and >80%, normal expression. The expression of CT antigen was performed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The expression of HLA class-I was normal in 49 tumors (36%), and there was reduced expression in 87 tumors (64%). The expression of Melanoma antigen (MAGE)-A3, MAGE-A4, and Kita-Kyushu lung cancer antigen-1 (KK-LC-1) was positive in 34 (25.0%), 22 (16.2%), and 42 (30.9%) patients, respectively. There was no significant difference in the proportion of HLA class-I expression associated with the expression of any of the CT antigens. Among the patients with positive expression of at least one of the CT antigens, the 5-year survival rate of the patients with the normal expression of HLA class-I was 87.5%; however, it was 63.4% in patients with the reduced expression of HLA class-I (p=0.0477). CONCLUSION: Reduced expression of HLA class-I was an unfavorable prognostic factor in patients with positive expression of CT antigen, and represents an important hurdle to antigen-based cancer immunotherapy.


Subject(s)
Adenocarcinoma/mortality , Antigens, Neoplasm/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Squamous Cell/mortality , Histocompatibility Antigens Class I/metabolism , Lung Neoplasms/mortality , Membrane Proteins/metabolism , Adenocarcinoma/immunology , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/genetics , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Histocompatibility Antigens Class I/genetics , Humans , Immunoenzyme Techniques , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Male , Membrane Proteins/genetics , Middle Aged , Neoplasm Staging , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Survival Rate , Testis/metabolism
3.
Lung Cancer ; 74(1): 112-7, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21397974

ABSTRACT

PURPOSE: This study investigated the preoperative serum levels of CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer. SUBJECTS: This study evaluated 341 patients who had undergone a complete resection for stage I NSCLC between 2002 and 2008. RESULTS: The patients included 193 males and 148 females. The mean age of the patients was 69.2 years (range: 19-88). The histological types included 264 adenocarcinomas, 56 squamous cell carcinomas, 11 large cell carcinomas, and 10 other types of carcinoma. A pneumonectomy was performed in 2 patients, a bilobectomy in 7, a lobectomy in 255, a segmentectomy in 46, and partial resection of the lung in 31 patients. The positive rates for CYFRA 21-1 in the adenocarcinoma and squamous cell carcinoma patients were 33.3% and 76.8%, respectively. The positive rates for CEA in adenocarcinoma and squamous cell carcinoma patients were 23.8% and 26.8%, respectively. The 5-year survival rate after surgery in the normal CYFRA 21-1 group and the high CYFRA 21-1 groups were 92.8% and 75.4%, respectively, in the patients with stage I NSCLC. There was a significant difference between the 2 groups (p<0.0001). The 5-year survival rate according to the serum level of CEA in the patients with stage I NSCLC were 88.3% for the normal group and 76.3% for the high group. In a multivariate analysis using the variables found to be significant prognostic factors in univariate analysis, a high CYFRA 21-1 level was found to be a significant independent prognostic factor (95% confidence interval 1.213-5.442, p=0.014). CONCLUSION: A high preoperative CYFRA 21-1 level was a significant independent prognostic factor in patients with stage I NSCLC. The patients with a high CYFRA 21-1 level should carefully followed-up to rule out occult metastasis. Further clinical studies will be necessary to evaluate the efficacy of adjuvant therapy for the patients selected according to this criterion.


Subject(s)
Antigens, Neoplasm/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/diagnosis , Keratin-19/metabolism , Lung Neoplasms/diagnosis , Receptors, Cell Surface/metabolism , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/genetics , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/physiopathology , Disease Progression , Female , Humans , Keratin-19/genetics , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Male , Middle Aged , Neoplasm Staging , Preoperative Care , Prognosis , Receptors, Cell Surface/genetics , Survival Analysis
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