Histologic-type specific role of cell cycle regulators in non-small cell lung carcinoma.

BACKGROUND: Lung cancer is the most lethal type of cancer in humans. Cell cycle alterations have commonly been encountered in lung cancer and may have prognostic value. MATERIALS AND METHODS: This study investigates the immunohistochemical expression of the important cell cycle regulators phosphatase and tensin homolog deleted on chromosome 10 (PTEN), p27, Cks1, and Skp2 in 128 non-small cell lung carcinomas (64 adenocarcinomas, 46 squamous cell carcinomas, and 18 large cell undifferentiated carcinomas) and adjacent non-neoplastic lung tissue. RESULTS: PTEN and p27 were always highly expressed in non-neoplastic lung whereas Cks1 and Skp2 were not expressed in normal tissue. Decreased PTEN expression was noted in 19/64 adenocarcinomas, 15/46 squamous cell carcinomas, and 7/18 undifferentiated large cell carcinomas. Reduced expression of p27 was noted in 28/64, 19/46, and 6/18 of the tumors, respectively. Increased expression of Cks1 was seen in 38/64, 26/46, and 11/18 and increased expression of Skp2 in 29/64, 30/46, and 14/18 of the tumors, respectively. An inverse relationship between p27 and Skp2 levels was found in adenocarcinomas and between p27 and Cks1 levels in squamous cell carcinomas. Decreased PTEN and p27 expression were associated with advanced tumor stage in squamous cell carcinomas. Univariate analysis showed that high p27 and PTEN and low Cks1 expression correlated with increased survival in patients with squamous cell carcinoma independently of tumor stage. CONCLUSIONS: Aberrant expression of PTEN, p27, Cks1, and Skp2 is a common feature of all three major types of non-small cell lung cancer NSCLC, but seems to be involved in the progression of squamous cell carcinoma alone.

Influence of blood transfusions and preoperative anemia on long-term survival in patients operated for non-small cell lung cancer.

It has been postulated that transfusions have immunosuppressive effects that promote tumor growth and metastasis. Moreover perioperative anemia is considered an independent prognostic factor on outcome in patients operated for malignancy. We evaluated the influence of red blood cell (RBC) transfusions and perioperative anemia on survival in non-small cell lung carcinoma (NSCLC) patients. From 1999 through 2005, 331 consecutive patients, male/female=295/36 (mean age 64+/-9 years), who underwent radical surgery for NSCLC were prospectively enrolled in this cohort and followed up for a mean of 27.2 months. The overall survival of patients was analyzed in relation to RBC transfusions and perioperative anemia. These parameters were analyzed in the whole cohort of patients and separately for stage I patients. Patients were divided according to perioperative transfusion, into Group A (transfused) and Group B (non-transfused) and according to the preoperative haemoglobin (Hb) level into Group 1(Hb<12g/dl) and Group 2(Hb> or =12g/dl), respectively. The overall transfusion rate was 25.7%. Univariate analysis showed that in the whole cohort of patients overall survival was significantly shorter in Group A (mean 33.6 months, 5-year survival 25.1%) compared to Group B (mean 48.0 months, 5-year survival 37.3%) (p=0.001). It also showed that patients with preoperative Hb level <12g/dl (Group 1), (mean of 33.0 months, 5-year survival 21.3%) had shorter survival compared to Group 2 patients (mean 49.3 months and 5-year survival 40.0%), respectively (p=0.002). Multivariate analysis in the whole cohort of patients showed that preoperative anemia was an independent risk factor for survival while RBC transfusion was not. In particular for stage I patients, it was shown that RBC transfusion was an independent prognostic factor for long-term survival as detected by multivariate analysis (p=0.043), while anemia was not. RBC transfusions affect adversely the survival of stage I NSCLC patients, while do not exert any effect on survival of patients with surgically resectable more advanced disease, where preoperative anemia is an independent negative prognostic factor. These findings indicate that RBC transfusion might exert an immunomodulatory effect on patients with early disease while in more advanced stages this effect is not apparent.

NSCLC and the alternative pathway of NF-κB: uncovering an unknown relation.

Lung cancer is the leading cause of cancer-related deaths worldwide. Although our knowledge on the pathobiology of the disease has increased in the last decades, the prognosis of lung cancer patients has hardly changed. Many signaling pathways are implicated in lung carcinogenesis, but the role of the alternative pathway of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in lung cancer pathogenesis and progression has not been investigated. The aim of our study was to investigate the role of this pathway in non-small cell lung cancer (NSCLC) patients. NF-κB2 and RelB protein expression was retrospectively assessed by immunohistochemistry in tissue samples from 109 NSCLC patients. RelB and NF-κB2 protein levels differed between tumors and adjacent nonneoplastic lung parenchyma. Cytoplasmic immunoreactivity of NF-κB2 and RelB was correlated with tumor stage (p = 0.03 and p = 0.016, respectively). In addition, cytoplasmic NF-κB2 levels were related to tumor grade (p = 0.046). Expression of RelB in the cytoplasm was tumor histologic type-specific, with squamous cell carcinomas having the highest protein levels. Nuclear expression of RelB and NF-κB2 differed between tumor and nonneoplastic tissues, possibly indicating activation of the alternative pathway of NF-κB in cancer cells. Moreover, lymph node metastasis was related to nuclear NF-κB2 expression in tumor cells. The deregulation of the alternative NF-κB pathway in NSCLC could play a role in the development and progression of the disease.

Low incidence of bronchopleural fistula after pneumonectomy for lung cancer.

Bronchopleural fistula (BPF) after pneumonectomy for NSCLC remains a highly morbid complication. We examined possible factors including the surgical techniques associated with BPF development. From 221 pneumonectomies for NSCLC, bronchial stump closure was mechanically performed in 192 patients and manually in the remaining 29. In all right-sided pneumonectomies mechanical closure was performed with associated stump coverage. In 114/130 left-sided procedures where mechanical closure was selected, bronchial stump remained uncovered. In the remaining 16 left-sided cases where manual stump closure was selectively performed, the stump was covered utilizing various tissues. Risk factors were classified into preoperative, intra-operative and postoperative. Five patients (2.3%) developed BPF. Univariate analysis revealed peri-operative transfusion, respiratory infection at the time of presentation, neoadjuvant therapy, right-sided pneumonectomy, manual type of bronchial closure, days of postoperative hospitalization and mechanical ventilation as significant risk factors for BPF development. Multivariate analysis followed revealing preoperative respiratory infection and right pneumonectomy as the only independent risk factors. In our series, a selected stump coverage policy showed a low incidence of BPF development. Mechanical stapling was superior to manual closure, although not as an independent factor. Early recognition of possible risk factors associated with fistula development is of paramount importance.

Large asymptomatic left atrial myxoma with ossification: case report.

BACKGROUND: Atrial myxomas are the most common primary cardiac tumors. They are usually small or moderate in size by the time of the diagnosis, exhibiting non specific cardiac or systemic symptoms, and are most frequently soft and friable without microscopic signs of ossification. We describe herein an extremely rare case of an asymptomatic giant left atrial myxoma with angiographic neovascularization and ossification. CASE PRESENTATION: An asymptomatic 58-year-old male with a giant left atrial tumor, was transferred to our Unit for surgical treatment. The tumor was an incidental finding during a work-up for hemoptysis due to bronchectasis. The coronary angiogram showed tumor vessels originating from the RCA. The tumor macroscopically did not resemble a myxoma, considering its dimensions (12 x 10 cm) and its solid substance. The mass was excised together with the interatrial septum and the right lateral LA wall close to the right pulmonary veins orifices. The defect was closed with Dacron patches in order to prevent malformation of both atria. The pathology study revealed a benign myxoma with excessive osteoid (mature bone) content. CONCLUSION: We consider our case as extremely rare because of the asymptomatic course despite the large size of the tumor, the blood supply from the right coronary artery and the bone formation.