Histological features of malignancy correlate with growth patterns and patient outcome in lung adenocarcinoma.

AIMS: Until the launch of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society adenocarcinoma classification in 2011, there were no uniform histological grading criteria for pulmonary adenocarcinomas. The current classification highlights the prognostic importance of the various histological growth patterns observed in these morphologically heterogeneous neoplasias. In this study, we aimed to evaluate the classic histological parameters of malignancy in correlation with the growth patterns and patient outcomes in a series of 112 surgically operated stage I-IV lung adenocarcinomas. METHODS AND RESULTS: Architectural growth pattern analysis was performed according to the current adenocarcinoma classification. Histological features including, for example, nuclear atypia, mitotic activity, tumour necrosis, and different patterns of invasion were assessed and correlated statistically with the architecture and the clinical data. A solid predominant histology was associated with increased levels of atypia (P = 0.027), mitotic activity (P < 0.001), necrosis (P < 0.001), and lymphovascular invasion (P = 0.001), and a non-predominant solid pattern was associated with intra-alveolar tumour spread (P = 0.004). The presence of a non-predominant lepidic tumour component showed inverse correlations with atypia (P = 0.002), mitotic rate (P = 0.009), and tumour necrosis (P < 0.001). Tumour size (P < 0.001), mitotic activity (P = 0.019), tumour necrosis (P = 0.002), lymphovascular invasion (P = 0.001) and visceral pleural involvement (P = 0.001) were all associated with reduced disease-specific survival. CONCLUSIONS: The classic histological features of malignancy correlate with tumour architecture and patient outcome, confirming the prognostic value of the growth pattern analysis and questioning the need for a parallel grading system in pulmonary adenocarcinoma.

[Pathology is much more than tumor diagnostics]. / Patologia on muutakin kuin kasvaindiagnostiikkaa.

For the most part, a pathologist's work consists of other than tumor samples. Inflammatory and degenerative diseases are classified according to etiology and character into groups differing significantly in their treatment and prognosis. In these diseases, histopathologic analysis continues to be one of the most important tools for their classification and assessment of the degree of severity. Even a negative finding assists in directing further investigations and follow-up. The development of new analysis methods along with new marker substances has helped to find even novel disease groups such as IgG4-associated inflammatory diseases.

Snail promotes an invasive phenotype in lung carcinoma.

BACKGROUND: Snail is a transcriptional factor which is known to influence the epitheliomesenchymal transition (EMT) by regulating adhesion proteins such as E-cadherin and claudins as well as matrix metalloproteases (MMP). METHODS: To evaluate the functional importance of snail, a transciptional factor involved in EMT in lung tumors, we investigated its expression in a large set of lung carcinomas by immunohistochemistry. Expression of snail and effects of snail knockdown was studied in cell lines. RESULTS: Nuclear snail expression was seen in 21% of cases this being strongest in small cell lung carcinomas (SCLC). There was significantly greater snail expression in SCLC compared to squamous cell or adenocarcinoma. Positive snail expression was associated with poor survival in the whole material and separately in squamous cell and adenocarcinomas. In Cox regression analysis, snail expression showed an independent prognostic value in all of these groups. In several cell lines knockdown of snail reduced invasion in both matrigel assay and in the myoma tissue model for invasion. The influence of snail knockdown on claudin expression was cell type specific. Snail knockdown in these cell lines modified the expression of MMP2 and MMP9 but did not influence the activation of these MMPs to any significant degree. CONCLUSIONS: The results show that snail plays an important role in the invasive characteristics of lung carcinoma influencing the survival of the patients. Snail knockdown might thus be one option for targeted molecular therapy in lung cancer. Snail knockdown influenced the expression of claudins individually in a cell-line dependent manner but did not influence MMP expressions or activations to any significant degree.

[Congenital ciliary dysfunction in children]. / Värekarvojen synnynnäiset toimintahäiriöt lapsilla.

Congenital ciliary dysfunctions are recessively inherited disorders. The disorder is poorly recognized, if the patient has no situs inversus. The diagnosis is delayed, being made on the average at the age of over five years. The review deals with a recent European multinational survey of the occurrence, genetics, diagnostics and treatment of congenital ciliary dysfunctions. Data of Finnish pediatric patients under treatment have also been collected for the survey. The number of congenital ciliary dysfunctions found in Finland is approximately one fifth of that found in other Nordic countries.

Variability in the precursor proteins of collagen I and III in different stages of COPD.

BACKGROUND: Levels of precursor proteins of collagen I and III are increased in fibrotic pulmonary diseases. This study determined whether the expression of precursors of type I and III collagen proteins would be increased in small and large airways of COPD patients in various stages of the disease reflecting fibrogenesis. METHODS: The levels of precursor proteins of collagen I and III were studied by immunohistochemistry and quantified by image analysis in lung tissue of 16 non-smokers, 20 smokers with normal lung function, 20 smokers with stage I-II COPD and 8 ex-smokers with stage IV COPD. RESULTS: In large airways, the subepithelial layer which was positive for precursor proteins of collagen I and III was thicker in smokers and in stage I-II COPD compared to non-smokers. Large airways in stage IV COPD showed reduced expression of precursor protein of collagen I whereas precursor of collagen III was increased. The amount of precursor protein of collagen III was increased in small airways of smokers and stage I-II COPD but reduced in stage IV COPD. CONCLUSIONS: Precursor proteins of collagen I and III revealed different expression profiles in large and small airways in various stages of COPD. Smoking enhanced expression of both precursors in large airways with a positive correlation with pack-years.

Ultrastructural features of lung fibroblast differentiation into myofibroblasts.

Fibroblast differentiation into myofibroblast in transforming growth factor-beta1-exposed human lung fibroblasts and the immunolocalizations of alpha-smooth muscle actin, fibronectin, tenascin-C, and osteopontin in exposed cells were studied by conventional transmission electron microscopy and immunoelectron microscopy. Ultrastructural features of myofibroblasts were detected after exposure, e.g., alpha-smooth muscle actin positive bundles in the cytoplasm of cells and extracellular fibronectin-containing structures on the surface of the cell forming fibronexus structure, osteopontin adjacent to rough endoplastic reticulum and extracellular tenascin-C in the vicinity of the cell. The authors concluded that exposure to transforming growth factor-beta1 can differentiate lung fibroblasts into ultrastructurally typical myofibroblasts.

Does the oxidative stress in chronic obstructive pulmonary disease cause thioredoxin/peroxiredoxin oxidation?

The thioredoxin/peroxiredoxin system comprises a redox-regulated antioxidant family in human lung; its significance, regulation, or oxidation has not been evaluated in smoking-related lung diseases. Here, we present the expression of the thioredoxin/peroxiredoxin system in lung biopsies from normal lung (n = 14), smokers (n = 21), and patients with chronic obstructive pulmonary disease (COPD, n = 38), and assess the possible inactivation/oxidation of this system by nonreducing Western blotting, two-dimensional gel electrophoresis, and mass spectrometry. Our study shows that the thiol status of the Trx/Prx-system can be modulated in vitro, but it appears to have high resistance against the oxidative stress in COPD.

Matrix metalloproteinase-9 (MMP-9) immunoreactive protein in urinary bladder cancer: a marker of favorable prognosis.

BACKGROUND: [corrected] The purpose of this study was to explore whether changes in matrix metalloproteinase-9 (MMP-9) are involved in the progression of urinary bladder cancer and whether they have any prognostic value. PATIENTS AND METHODS: Overexpression of MMP-9 was evaluated in the primary tumor of 87 urinary bladder cancer cases with immunohistochemical staining. RESULTS: Of the urinary bladder carcinomas, 38% showed an overexpression (>25%) of MMP-9 immunoreactive protein. Increased positivity for MMP-9 correlated with favorable overall survival of the urinary bladder cancer patients. The 5-year overall survival and relapse-free survival was 68% and 36% in patients showing high MMP-9 expression and 48% and 19% in patients with low (<25%) or negative MMP-9 expression (p=0.006, p=0.08, respectively). In multivariate analysis, MMP-9 overexpression seems to retain its independent prognostic value. CONCLUSION: This study shows that MMP-9 expression in urinary bladder carcinoma is associated with better prognosis.

Extracellular matrix proteins and myofibroblasts in granulomas of sarcoidosis, atypical mycobacteriosis, and tuberculosis of the lung.

Sarcoidosis, atypical mycobacteriosis, and tuberculosis are common diseases of human lung with a typical feature of formation of granulomas. The structure of granulomas has not been elucidated completely. We studied the expression of tenascin-C, precursor proteins of collagens I and III, and the presence of myofibroblasts in granulomas of sarcoidosis, atypical mycobacteriosis, and tuberculosis of human lung. Twenty-five histologic samples of lung were analyzed by immunohistochemistry using antibodies to tenascin-C and aminoterminal propeptides of collagens I and III. To identify the myofibroblast-type cells in granulomas, the sections were also stained with antibodies against alpha-smooth muscle actin, vimentin, and desmin. In every case, tenascin-C and precursor proteins of collagens I and III were expressed around granulomas. Precursor protein of collagen I was expressed also within them. In tuberculosis and atypical mycobacteriosis, expression of tenascin-C and precursor protein of collagen I was stronger than in sarcoidosis. The cells demarcating granulomas and, thus, colocalizing with tenascin-C and both collagen precursors were positive for alpha-smooth muscle actin and vimentin, which suggests that these cells are myofibroblasts. They were also more abundantly present in tuberculosis and atypical mycobacteriosis, as suggested by alpha-smooth muscle actin staining. We concluded that tenascin-C and precursor proteins of collagens I and III are expressed around granulomas in sarcoidosis, atypical mycobacteriosis, and tuberculosis of the lung; and furthermore, their expression colocalize with the expression of myofibroblasts. Our results further point to the fact that fibrogenesis and matrix turnover is stronger in tuberculosis and atypical mycobacteriosis than in sarcoidosis.

Low serum level of pro-matrix metalloproteinase 2 correlates with aggressive behavior in breast carcinoma.

Malignant tumors that are capable of invading surrounding structures and metastasizing possess certain capacities to cross tissue barriers. Matrix metalloproteinases (MMPs), especially gelatinases and their inhibitor molecules, are known to affect the extracellular matrix turnover, and the proteolytic imbalance due to the abnormal expression of these enzymes eventually leads to cancer progression. This has been well documented at the tissue level. In this study, the different forms of the circulating MMP-2 have been studied in the preoperative sera of 71 patients with breast carcinoma. A quantitative enzyme-linked immunosorbent assay was performed for total proMMP-2, proMMP-2-tissue inhibitor of metalloproteinase 2 (TIMP-2) complex, and free active MMP-2. It is shown here, for the first time, that the total proMMP-2 levels in the serum correlate inversely with node positivity, high stage of the disease, and high nuclear grade of the breast tumor. An association with the levels of lower free active MMP-2 and tumor recurrence is also demonstrated. Interestingly, the tumor tissue expression of MMP-2 had an inverse correlation with proMMP-2-TIMP-2 complex levels in the serum. In conclusion, the levels of the total proMMP-2 correlate inversely with tumor burden, whereas free active MMP-2 might be associated with survival. This could indicate that the prognostic value of the circulating forms of MMP-2 is not congruent with the prognostic information obtained from tissue expression. This is further supported by the inverse correlation of the proMMP-2-TIMP-2 complex and MMP-2 tissue expression in the tumor. Therefore, the different forms of circulating metalloproteinases need to be evaluated further to explore their full potential for clinical use.

Nitric oxide synthases are associated with bronchial dysplasia.

Recent studies suggest that reactive oxygen (ROS) and nitrogen species (RNS) are highly associated with the pathogenesis of cigarette smoke related lung diseases but their role in the malignant conversion of bronchial epithelium is unclear. The immunohistochemical expression of inducible, endothelial and neuronal nitric oxide synthases (iNOS, eNOS and nNOS) and nitrotyrosine as a biomarker of oxidative/nitrosative stress was evaluated in 79 cases including 13 non-smokers, 20 smokers without chronic obstructive pulmonary disease (COPD), 22 with COPD and 24 with metaplasia-dysplasia-sequence of the bronchial epithelium. Normal lung of non-smokers was mainly negative for nitrotyrosine, while it was higher in the alveolar macrophages of cigarette smokers and COPD than in non-smokers (p=0.025, p<0.001), and in the alveolar epithelium of smokers and COPD than in non-smokers (p=0.049). There were no major differences in the nitrotyrosine immunoreactivity between the metaplastic/dysplastic lesions and bronchial epithelium of cigarette smokers. Inducible NOS and nNOS were mainly non-detectable or weak in the normal looking bronchial epithelium of smokers and COPD, whereas metaplasia and dysplasia showed positivity for iNOS (22/24) and nNOS (14/24) in the majority of cases. Strong immunoreactivity for iNOS and nNOS was also found more often in dysplastic than metaplastic (p=0.011 and p=0.049, respectively) specimens. Thus, smoking can cause protein nitration also in normal lung. Prominent iNOS and nNOS immunoreactivity in the metaplasia-dysplasia-lesions suggests a divergent role of NOSs in lung carcinogenesis.

COX-2 is widely expressed in metaplastic epithelium in pulmonary fibrous disorders.

Idiopathic usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) and asbestosis represent progressive and often fatal pulmonary fibrous disorders, whereas cryptogenic organizing pneumonia (COP), desquamative interstitial pneumonia (DIP), and respiratory bronchiolitis-interstitial lung disease (RB-ILD) usually are reversible or nonprogressive conditions. Prostaglandin E2 (PGE2) inhibits fibroblast proliferation and myofibroblast transition, its production depending on cyclooxygenase-2 (COX-2). In patients with UIP/IPF, levels of PGE2 and COX-2 are reduced in fibroblasts, and levels of PGE2 in bronchioalveolar lavage fluid may be lowered. We analyzed the immunohistochemical expression of COX-2 in UIP/IPF, asbestosis, COP, DIP, and RB-ILD. Our results show that the metaplastic epithelium in UIP/IPF, asbestosis, and COP is widely COX-2+, whereas COX-2 positivity is scant in DIP and RB-ILD. The mesenchymal cells remained negative. Our results suggest that irrespective of the underlying disease, lung injury that causes extensive fibrosis induces wide expression of COX-2 in the regenerating metaplastic epithelium.

Tissue inhibitor of matrix metalloproteinase-1 is prognostic in head and neck squamous cell carcinoma: comparison of the circulating and tissue immunoreactive protein.

PURPOSE: Tissue inhibitors of metalloproteinases (TIMP) are capable of inhibiting the matrix metalloproteinases, but they also possess other biological functions. Little is known about the role of TIMP-1 in the progression and spreading of cancer cells among patients with head and neck squamous cell carcinoma (HNSCC). In this study, the pretreatment serum levels of TIMP-1 or the overexpression of TIMP-1 immunoreactive protein in the primary tumor was correlated to the clinical course in patients with HNSCC. EXPERIMENTAL DESIGN: The TIMP-1 immunoreactive protein was studied in 74 cases representing HNSCC. The tissue immunoreactive protein was evaluated from paraffin-embedded tumor sections in 68 cases using immunohistologic staining with a specific antibody, and in 68 cases the pretreatment serum levels of TIMP-1 were quantitatively measured by ELISA assay. The results were compared with the clinicopathologic factors of the disease and the patients' outcome. RESULTS: A positive correlation was found between the size of the primary tumor (T) and the circulating TIMP-1 level (P = 0.021) or the positive immunoreaction of TIMP-1 in tumor (P = 0.039). The 5-year cause-specific survival was significantly lower in patients presenting with a high serum TIMP-1 level than in those with a low level of TIMP-1 (38% versus 64%, P = 0.034). They also had an unfavorable 5-year relapse-free survival rate (37% versus 56%, respectively). Similarly, the expression of TIMP-1 in tumor was prognostic for shortened survival, the 5-year cumulative relapse-free survival being 42% in patients with a TIMP-1-positive tumor versus 75% in cases with a negative tumor (P = 0.035). Tissue TIMP-1 positivity also seemed associated to the cause-specific survival (P = 0.075) and to be connected with later lymph node or hematogenic relapses. CONCLUSIONS: This study shows for the first time that both circulating and tissue TIMP-1 immunoreactive protein predicts the clinical course and dissemination in HNSCC, suggesting that TIMP-1 might be related to both tumor growth and metastasis in HNSCC.

Mesotheliomas show higher hyaluronan positivity around tumor cells than metastatic pulmonary adenocarcinomas.

Hyaluronan is a unique glycosaminoglycan of the extracellular matrix, abundant in normal connective tissues but highly increased in many pathological conditions like cancer. Mesothelioma, one of the most malignant cancer types, is associated with high content of hyaluronan, with elevated levels of hyaluronan in pleural effusions and serum of the patients. Metastatic lung adenocarcinomas are typically less aggressive and have a better prognosis as compared to mesotheliomas, a reason why it is highly important to find reliable tools to differentiate these cancer types. The main purpose of this study was to evaluate the amount of hyaluronan, hyaluronan producing synthases (HAS's) and hyaluronan receptor CD44, in mesothelioma and metastatic lung adenocarcinomas. Furthermore, we wanted to clarify the role of hyaluronan, CD44 and HAS's as putative markers for differentiating malignant mesothelioma from metastatic lung adenocarcinomas. The main finding of this study was that mesotheliomas are significantly more positive for hyaluronan staining than metastatic adenocarcinomas. Unexceptionally, a trend of CD44 positivity of stromal cells was higher in adenocarcinomas as compared to mesotheliomas. However, no statistically significant differences were found between the staining of any of the HAS isoenzymes either in tumor cells or stromal cells of different groups of cases. The results show that there are significant differences in hyaluronan content between metastatic lung adenocarcinomas and mesotheliomas. However, as previous studies have suggested, hyaluronan alone is not a sufficient independent marker for diagnostic differentiation of these cancer types, but could be utilized as a combination together with other specific markers.

Progression of human aortic valve stenosis is associated with tenascin-C expression.

OBJECTIVES: We sought to assess tenascin-C (TN-C) expression and its possible pathobiological impact in human aortic valve stenosis. BACKGROUND: Tenascin-C, a large extracellular matrix glycoprotein, has lately been increasingly connected to cardiovascular pathologies. As TN-C is a multifunctional protein implicated in cell proliferation, migration and differentiation, we investigated the pattern of its expression in diseased human aortic valves. METHODS: Fifty-five tricuspid, non-rheumatic stenotic aortic valves were collected from patients undergoing aortic valve replacement, and the controls consisted of four normal valves from individuals who had suffered traumatic death and one from a patient operated on because of a noncalcified purely regurgitant valve. A monoclonal mouse antibody to human TN-C (143DB7) was used as the primary antibody in immunostaining. To study the source of TN-C messenger RNA synthesis, some tissue samples were also examined using in situ hybridization. In order to identify smooth muscle cell differentiation, commercially available antibodies against alpha-smooth muscle actin were used, and immunophenotypic analysis of inflammatory cells was carried out by using the monoclonal mouse antibodies UCHL-1, L26 and PGM-1. RESULTS: In normal valves, TN-C expression was associated with the basement membrane beneath the endothelial cells, whereas stenotic valves showed no such expression but rather immunoreactivity in the deeper layers of the valves. This reactivity was associated with the characteristics typical of the stenosing process and the increased mechanical loading caused by hypertension. CONCLUSIONS: We hypothesize that the overexpression of TN-C in stenotic human aortic valves may emphasize that this disease is an active rather than a degenerative process.

Thoracoscopic lung biopsy is a safe procedure in diagnosing usual interstitial pneumonia.

OBJECTIVES: To evaluate the effect of lung biopsy on the survival of patients when histopathologic confirmation of usual interstitial pneumonia (UIP) is needed. BACKGROUND: Idiopathic pulmonary fibrosis is a distinct clinical entity with histopathologic features of UIP. Surgical biopsy is needed when clinical and radiologic findings are not typical. The safety of lung biopsy is a matter of debate, and the results of short-term mortality (< 30 days) after biopsy are variable. METHODS: Seventy-six patients with UIP, including 34 patients who underwent video-assisted thoracoscopic surgery (VATS) biopsy and 42 patients who underwent open-lung biopsy, were included in this retrospective study. All biopsies were reevaluated for UIP histopathology. Clinical data such as age at the time of biopsy, type of biopsy, preoperative pulmonary function, major postoperative complications, date and cause of death, and survival time after the biopsy were gathered. Median survival was used to compare the survival between different groups, and cumulative survival was estimated using Kaplan-Meyer method. RESULTS: Thoracoscopic biopsy was safe for diagnosing UIP, with no short-term mortality. In contrast, open-lung biopsy was followed by four deaths (5.3%) within 1 month after the procedure. All fatal cases were accompanied by a histopathologic pattern of diffuse alveolar damage. Age of the patient at the time of biopsy was a significant predicting factor for survival. Patients < 50 years old lived 181 months (range, 119 to 242 months), and patients > 50 years old lived 75 months (range, 55 to 95 months). CONCLUSIONS: VATS biopsy is a safe procedure in diagnosing UIP.

Localization of precursor proteins and mRNA of type I and III collagens in usual interstitial pneumonia and sarcoidosis.

The aim of this study was to assess and compare the accumulation and distribution of newly synthesized type I and III collagens in usual interstitial pneumonia (UIP) and pulmonary sarcoidosis. Lung biopsies from 10 patients with UIP and 13 patients with sarcoidosis were investigated by immunohistochemical technique and mRNA in situ hybridization. The antibodies for the aminoterminal propeptide of type I procollagen and the aminoterminal propeptide of type III procollagen (PINP and PIIINP, respectively) were used. When compared to healthy lung, levels of type I pN- and type III pN-collagens were increased in both of these disorders. Type I procollagen was mostly present as intracellular spots in newly formed fibrosis in UIP while type III pN-collagen was expressed extracellularly underneath metaplastic alveolar epithelium. Type I procollagen was present intracellularly within and around the granulomas of sarcoidosis, whereas type III pN-collagen was expressed extracellularly, mainly around the granulomas. mRNAs of both collagens colocalized with the precursor proteins. We conclude that the expression of precursor proteins and mRNA of type I and type III collagens is increased in UIP and sarcoidosis, reflecting mainly active synthesis of these collagens in different areas of the lung.

Expression of matrix metalloproteinase-9 in head and neck squamous cell carcinoma: a potential marker for prognosis.

PURPOSE: Previous studies have shown that matrix metalloproteinase-9 (MMP-9) is expressed in malignant head and neck squamous cell carcinoma. The prognostic role of MMP-9 is still unclear. The aim of this study was to investigate the role of MMP-9 immunoreactive protein as a prognostic marker for survival in head and neck squamous cell carcinoma. EXPERIMENTAL DESIGN: Overexpression of the immunoreactive protein for MMP-9 was evaluated in tissue sections of 74 primary head and neck carcinomas with a monoclonal antibody using a biotin-streptavidin immunohistochemical staining method. The staining results were compared with the clinical data and to the patients' outcome. RESULTS: Positive immunostaining for MMP-9 was observed in 82% of the head and neck carcinomas, 39% of the cases being extensively positive. MMP-9 protein expression was independent of the stage or the grade of the tumor. The expression of MMP-9 was prognostic for shortened survival, the 5-year cause-specific survival being 45% in MMP-9 positive cases, and 92% in cases negative for MMP-9 (P = 0.013). MMP-9 positivity also correlated to the relapse-free survival (P = 0.019). At the 5-year follow-up, the cumulative relapse-free survival rate was 79% for patients with MMP-9-negative tumor and 42% for the patients with positive immunostaining for MMP-9. High expression of MMP-9 seemed to be linked with more aggressive relapses, appearing in 33% of the cases in local relapses, in 52% of cases with lymph node relapses, and in 60% of the cases with hematogenic relapses. CONCLUSIONS: This is the first study with a long follow-up showing that the immunoreactive protein of MMP-9 in head and neck carcinoma is associated with shortened relapse-free and cause-specific survival, suggesting that MMP-9 has a role in tumor progression of head and neck carcinomas, as well as in estimation of the prognosis of these diseases.

Claudin-5 is associated with elevated TATI and CA125 levels in mucinous ovarian borderline tumors.

BACKGROUND/AIM: Claudin proteins represent a large family of integral membrane proteins crucial for tight junction (TJ) formation and function and are abnormally regulated in several human cancers. The aim of the present study was to study the expression levels of claudin-5 in pre-malignant disease as borderline mucinous ovarian tumors. Previous reports have suggested that claudin-5 over-expression correlates with aggressive behaviour in serous ovarian adenocarcinoma, breast cancer and in pancreatic andenocarcinoma. PATIENTS AND METHODS: We investigated the expression of claudin-5 in mucinous ovarian borderline tumors and its correlation with clinico-pathological parameters and the expression of serum markers cancer antigen (CA) 125 and tumor-associated trypsin inhibitor (TATI). RESULTS: A total of 29 mucinous borderline tumor tissue samples were analyzed using immunohistochemical staining for claudin-5. An association between strong claudin-5 expression and higher serum levels of TATI (p=0.04) and CA125 (p=0.008) were found. There was also an association between claudin-5 expression and the presence of ascites (p=0.02). CONCLUSION: Changes in claudin-5 expression may play a role in malignant transformation.

Antioxidant enzymes and redox regulating thiol proteins in malignancies of human lung.

Oxidants are known to modulate cell proliferation and apoptosis, and induce synthesis of growth factors that play an important role in tumor growth and invasion. Antioxidant enzymes and thiol proteins regulating cellular redox state constitute the major cellular protection against oxidants. Consequently, they are also associated both with carcinogenesis and tumor progression. Superoxide dismutases, glutamate cysteine ligase, catalase, thioredoxins and peroxiredoxins, which are the most important of these enzymes, are expressed in lung malignancies, and especially in pleural mesothelioma. This has consequences not only for tumor behavior but also for resistance of tumor cells to cytotoxic drugs and radiation.