The expression patterns and prognostic significance of pleckstrin homology-like domain family A (PHLDA) in lung cancer and malignant mesothelioma.

BACKGROUND: Pleckstrin homology domain family A (PHLDA) genes play important roles in cancer cellular processes, including inhibiting Akt activation, repressing growth factor signaling, inhibiting the negative feedback of EGFR/ErbB2 signaling cells, and inducing apoptosis. However, the prognostic significance of PHLDA in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MM) remains unclear. The present study investigates the associations between PHLDA expression patterns and their prognostic value in lung adenocarcinoma (LUAD) and MM. METHODS: We analyzed PHLDA family members at the genomic level in silico to explore their mRNA expression pattern and predictive significance in LUAD and MM. We then created a PHLDA-drug interaction network and a protein-protein interaction (PPI) network using different databases. Finally, we immunohistochemically assessed the protein expression of each PHLDA family member on tissue microarrays (TMAs) in both LUAD and MM cohorts with long-term follow-up. RESULTS: While PHLDA1 mRNA expression in both LUAD and MM was lower than that of normal tissue, PHLDA2 mRNA was significantly overexpressed in LUAD, and PHLDA3 mRNA was overexpressed in MM. In NSCLC, both low PHLDA1 mRNA expression and high PHLDA3 mRNA expression correlated with worse overall survival (OS) (P<0.01), whereas high PHLDA2 mRNA expression was associated with better OS (P<0.01). In MM, patients presenting high PHLDA1 and PHLDA2 mRNA expression had poor OS (P=0.01 and P<0.01, respectively). In addition, the PHLDA-drug interaction network indicated that several common drugs could potentially modulate PHLDA expression, and the PPI network suggested that PHLDA1 interacts with Notch family members, whereas PHLDA3 interacts with TP53. Our results also showed that the expression of PHLDA2 and PHLDA3 was significantly higher in LUAD and MM than that of PHLDA1 (P<0.05) and was associated with the risk of death. While patients with PHLDA2 >85.09 cells/mm2 had a low risk of death (P=0.01) and a median survival time of 48 months, those with PHLDA3 <70.38 cells/mm2 had a high risk of death (P=0.03) and a median survival time of 34 months. CONCLUSIONS: We shed light on the role of the PHLDA family as promising predictive biomarkers and potential therapeutic targets in LUAD and MM.

Lung cyst: an unusual manifestation of Niemann-Pick disease.

Niemann-Pick disease is a rare inherited autosomal recessive disorder, currently classified into six subtypes and characterized by the intracellular accumulation of sphingomyelin in the liver, spleen, lungs, bone marrow or brain. The main pulmonary abnormalities described in high-resolution computed tomography (HRCT) of the chest consist of thickening of the interlobular septa and ground-glass opacities. This case report describes a patient with subtype B Niemann-Pick disease characterized by cysts and ground-glass opacities that were detected on HRCT of the chest.

Prognostic relevance of TTF-1 and MMP-9 expression in advanced lung adenocarcinoma.

BACKGROUND: The thyroid transcription factor-1 (TTF-1) is a tissue-specific transcription factor that could play an important role in cell differentiation and morphogenesis of lung tumors. Matrix metalloproteinase-9 (MMP-9) is a protease commonly expressed in non-small cell lung cancer, conferring angiogenic and metastatic potential. METHODS: We assessed TTF-1 and MMP-9 tumor expression by immunohistochemistry in 51 patients with lung adenocarcinoma, stage IIIB or IV, treated with platinum regimens. A bicategorical prognostic model was obtained using the Kaplan-Meier method, Cox regression, and conjunctive consolidation. RESULTS: The median expression of TTF-1 was 30.0% (range: 0-85.9%). All tumors expressed MMP-9 (median: 78.7%; range: 15.2-96.1%). Median survival was 41.6 weeks, with estimated 1- and 2-year survival rates of 45.0% and 22.0%, respectively. Poor performance status (Karnofsky scale) - hazards ratio (HR): 1.03, 95% confidence interval (CI): 1.01-1.06; low TTF-1 expression (<40%) - HR: 4.00, 95% CI: 1.75-9.09; and high MMP-9 expression (> or =80%) - HR: 2.82, 95% CI: 1.30-6.08 were independent prognostic factors. Patients could be stratified in three death risk groups according to markers expression: low risk (high TTF-1 and low MMP-9; median survival: 127.6 weeks), intermediate risk (low TTF-1 or high MMP-9; median survival: 39.0 weeks); and high risk (low TTF-1 and high MMP-9; median survival: 16.4 weeks). CONCLUSION: TTF-1 and MMP-9 tumor expression as detected by immunohistochemistry may allow identification of different, clinically meaningful, prognostic groups of advanced lung adenocarcinoma patients treated with platinum regimens.

Lung cancer symptoms and pulse oximetry in the prognostic assessment of patients with lung cancer.

BACKGROUND: Medical oncologists continue to use performance status as a proxy for quality of life (QOL) measures, as completion of QOL instruments is perceived as time consuming, may measure aspects of QOL not affected by cancer therapy, and interpretation may be unclear. The pulse oximeter is widely used in clinical practice to predict cardiopulmonary morbidity after lung resection in cancer patients, but little is known on its role outside the surgical setting. We evaluated whether the Lung Cancer Symptom Scale and pulse oximetry may contribute to the evaluation of lung cancer patients who received standard anticancer therapy. METHODS: We enrolled forty-one consecutive, newly diagnosed, patients with locally advanced or metastatic lung cancer in this study. We developed a survival model with the variables gender, age, histology, clinical stage, Karnofsky performance status, wasting, LCSS symptom scores, average symptom burden index, and pulse oximetry (SpO2). RESULTS: Patient and observer-rated scores were correlated, except for the fatigue subscale. The median SpO2 was 95% (range: 86 to 98), was unrelated to symptom scores, and was weakly correlated with observer cough scores. In a multivariate survival model, SpO2 > 90% and patient scores on the LCSS appetite and fatigue subscales were independent predictors of survival. CONCLUSION: LCSS fatigue and appetite rating, and pulse oximetry should be studied further as prognostic factors in lung cancer patients.

A rare cause of hemoptysis: benign sugar (clear) cell tumor of the lung.

A case of benign sugar (clear) cell tumor of the lung with an unusual clinical presentation and its evaluation with computed tomography are reported. A 48-year-old man presented with one episode of hemoptysis. Chest radiographs revealed a round nodule in the lower left lung lobe, and fiberoptic bronchoscopy was normal. On the computed tomography scans, the nodule showed intense post-contrast enhancement (74.7 Hounsfield units). The patient underwent a left thoracotomy, and a segmentectomy was performed. Pathologic examination showed a benign sugar cell tumor of the lung. The patient is alive and has remained free of disease for the last 2 years. To the best of our knowledge, this is the first case report of sugar cell tumor located in lung parenchyma that presented with hemoptysis and the second report of the contrast-enhanced computed tomography findings in this neoplasm.