ABSTRACT
Previous studies suggest that some S100 proteins are involved in the progression of certain types of cancer. However, no comprehensive data is currently available on the expression of S100 family genes in lung adenocarcinomas. Oligonucleotide array, quantitative reverse transcription-polymerase chain reaction and western blot analyses of lung adenocarcinoma cell lines and bronchiolar epithelial cells (SAEC and NHBE) revealed that S100A2 and S100A4 were the most strikingly downregulated and upregulated members of the S100 family, respectively. Immunohistochemical analyses of 94 primary lung adenocarcinomas showed that positive S100A2 expression (33/94, 35.1%) was significantly associated with lymphatic invasion (P=0.0233) and positive S100A4 expression (19/94, 20.2%) with vascular invasion (P=0.0454). Interestingly, a strong inverse relationship was found between S100A4 and p53 expression (P=0.0008). Survival analyses showed that S100A4 positivity was associated with poor patient prognosis (P=0.042). S100A2 positivity was not associated with patient survival when the whole patient group was analyzed; however, S100A2 positivity was a favorable prognostic indicator in patients with p53-negative tumors (P=0.0448). Finally, we used oligonucleotide array analyses and identified potential S100A2 and S100A4 target genes involved in cancer progression: S100A2 induced RUNX3 and REPRIMO; S100A4 induced EZRIN, RUNX1 and WISP1; S100A2 repressed EGFR, NFKB2 and RELA2; and S100A4 repressed ANXA10 and IL1RN. Thus, the present study demonstrates involvement of S100A2 and S100A4 in the progression of lung adenocarcinomas and an inverse association between S100A4 and p53 expression, and provides a list of targets regulated by S100A2 and S100A4.
Subject(s)
Adenocarcinoma/genetics , Chemotactic Factors/genetics , Gene Expression Regulation, Neoplastic , Genes, p53 , Lung Neoplasms/genetics , S100 Proteins/genetics , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Base Sequence , Bronchi/cytology , Cell Line , Cell Line, Tumor , DNA Primers , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Respiratory Mucosa/cytology , Reverse Transcriptase Polymerase Chain Reaction/methods , S100 Calcium-Binding Protein A4 , Survival AnalysisABSTRACT
To clarify the association of the P27 degradation pathway proteins, Skp2 and Jab1, with the development and progression of lung adenocarcinoma (AD), we immunohistochemically investigated Skp2 and Jab1 expression together with P27- and Ki-67-labeling in 110 lung AD and 11 atypical adenomatous hyperplasia (AAH) and analyzed the relationship between the expression of these proteins and the clinicopathological factors. High Skp2 or Jab1 expression was frequent in lung AD (52/110, 47%, and 59/110, 54%, respectively), and high expression of Jab1 was also frequent in AAH (4/11, 36%), while it was not observed in normal bronchiolar epithelium. The P27 labeling index (LI) was reciprocally correlated with high Skp2 and Jab1 expression, and a higher Ki-67 LI was significantly correlated with high Skp2 and Jab1 expression. However, low P27 expression did not correlate with a higher Ki-67 LI. High Skp2 lung AD showed significant correlation with blood and lymphatic vessel invasion, which low P27 expression did not correlate with. Furthermore, high Skp2 expression in lung AD was significantly correlated with a poor outcome for patients. Thus, Skp2 and Jab1 regulate P27 degradation, and might contribute to the development and progression of lung AD through P27-mediated and -unmediated mechanisms.
Subject(s)
Adenocarcinoma/metabolism , Cell Cycle Proteins/metabolism , DNA-Binding Proteins/metabolism , Lung Neoplasms/metabolism , S-Phase Kinase-Associated Proteins/metabolism , Transcription Factors/metabolism , Tumor Suppressor Proteins/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , COP9 Signalosome Complex , Cell Count , Cyclin-Dependent Kinase Inhibitor p27 , Disease Progression , Female , Humans , Immunoenzyme Techniques , Intracellular Signaling Peptides and Proteins , Japan/epidemiology , Ki-67 Antigen/metabolism , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Peptide Hydrolases , Survival RateABSTRACT
Multiple bilateral pulmonary arterio-venous malformations (PAVM) were diagnosed in a 15-year-old girl with erythrocytosis. Although transcatheter embolotherapy is generally accepted as a treatment of PAVM, the largest lesion in the right lower lobe was fed by a 13-mm diameter feeding artery without downstream narrowing, which was unsafe for the embolization of coils or balloons. Instead, we surgically ligated the largest feeding artery under video-assisted thoracoscopy, without losing any lung parenchyma. The other PAVM were successfully treated by embolization of metallic coils. The arterial partial pressure of oxygen (O(2)) increased from 37 to 64mmHg on room air, and from 46 to 410mmHg on 100% O(2).
ABSTRACT
Thymic carcinoma was indistinct for criteria of clinicopathological diagnosis. Recently it gets easier to diagnose thymic carcinoma, because of progression of WHO classification and immunohistochemical technique. Commonly, patients are men and in sixties. Common symptoms are chest pain and dyspnea. Most cases are advanced, over Stage III of the Masaoka's classification. Combined therapies e.g. operation, chemotherapy and radiation were done, but complete resection is difficult. Prognosis is poor, the 3- and 5-year survival is 48.7% and 40.6%.
