Can Öztürk

Survivin expression in pre-invasive lesions and non-small cell lung carcinoma

Survivin is an inhibitor of apoptosis protein, which is overexpressed in many carcinomas, including lung carcinoma. The aim of this immunohistochemical study was to investigate the role of survivin in the early steps of lung carcinogenesis and non-small cell lung carcinomas (NSCLC), and its relationship with expression of p53 protein, a tumor suppressor gene involved in cell cycle control. In the normal bronchial epithelium, low-grade atypical adenomatous hyperplasia (AAH) and non-neoplastic lung parenchyma adjacent to tumor, survivin was found completely negative. Expression of survivin was detected in the areas of squamous metaplasia and dysplasia as well as high-grade AAH lesions adjacent to tumor. Survivin was expressed in 50 (64%) and p53 in 41 (53%) NSCLC. Survivin expression was significantly correlated with lymph node metastasis (p=0.02). There was no correlation between survivin and p53 expression. The patients with expression of survivin had significantly worse prognosis (Log-rank test, p=0.003). Multivariate Cox regression analysis showed TNM stage (p<0.001) and survivin expression (p=0.003) as independent prognostic indicators. In conclusion, survivin expression might be an early step in lung carcinogenesis. Survivin expression might also be used as a prognostic indicator predicting the worse outcome in NSCLC, and might be a novel target for the treatment of patients with preinvasive lesions of lung and NSCLC.

Genetic Variations in the Hypoxia-Inducible Factor-1αGene and Lung Cancer

Hypoxia-inducible factor-1 (HIF-1), an important genetic component of angiogenesis, becomes stable as a response to tumor hypoxia and facilitates tumor survival. The polymorphisms of the HIF-1αgene may cause changes in the activity of this protein, which serves as a transcription factor for many genes in tumorigenesis. In this study, we have investigated the relationship between seven HIF-1αpolymorphisms [C > T substitution in intron 8 (rs10873142), T418I (rs41508050) in exon 10, P564P (rs41492849), L580L (rs34005929), P582S (rs11549465), A588T (rs11549467) in exon 12 and dinucleotide GT repeats in intron 13 (rs10645014)] among lung cancer patients in the Turkish population. Genomic DNA was isolated from 141 lung cancer cases and 156 controls and subjected to PCR for amplification. Genotyping was carried out with RFLP and DNA sequencing methods. There was no significant difference between the lung cancer cases and controls in terms of the distribution of genotyping frequencies of seven HIF-1αpolymorphisms (P > 0.05). No significant relationship was found between the C > T substitution in intron 8 and P582S haplotypes and development of lung cancer. In addition, there were no significant associations between the genotypes and clinopathological characteristics of the cases examined. These findings show that polymorphisms in the HIF-1αgene do not confer susceptibility to lung cancer. Exp Biol Med 234:1109–1116, 2009

Hospital based survey of lung cancer in Turkey, a developing country, where smoking is highly prevalent.

While the trend of cigarette consumption in some developed countries is on the decline, it has been noted that in many developing countries, smoking is on the increase. Compared to developed countries, there are more male smokers than female smokers in these countries. The aim of this study was to investigate the prevalence and characteristics of the smoking habit in patients having lung cancer (LC) and to find out if there is any relationship with the smoking habit and the pathological diagnosis in our patient population. This hospital-based study was carried out between 1990 and 1996 in two major medical centres. LC was diagnosed in 1046 patients, 966 of whom were males (93%), and the remaining 80 (7%) of whom were females. Upon diagnosing the male patients, it was noted that 83% were current smokers (CS), 12% were ex-smokers (ES defined as abstinence from smoking at least for 1 year), and the remaining 5% were non-smokers (NS). In the female population the findings were as follows, 16% were CS; 8% were ES, and 76% were NS. The period of abstinence in the ES was 10 years or less in 77% of the patients. Among the male patients, squamous cell carcinoma was the most common tumor type seen in the CS group (46%) while adenocarcinoma (45%) was the most commonly seen tumor in the NS group. On the other hand, in the females, CS, the most commonly noted tumor types were small cell (54%), and adenocarcinoma (39%) was most frequently found in NS group. These results indicate that ES patients having LC in this study was quite low. On the other hand, in contrast to the findings of many other studies, from developed countries, the majority of male LC patients were in the CS group, however the majority of female LC patients were in the NS group. This smoking habit data obtained from our LC patients suggests that, similar to underdeveloped or developing countries, smoking cessation rates are very low in men during the past decade, and interestingly smoking rates may increase in women in the near future in our country.

Malignant pleural mesothelioma with scalp, cerebellar, and finger metastases: a rare case.

Malignant pleural mesothelioma (MPM) is a rare and asbestosis-associated tumor. MPM commonly invades locally, mostly in the lung, heart, pericardium, chest wall, and vertebrae. Distant metastasis of MPM is very rare. Here we report a patient with MPM who presented with multiple unusual distant metastases. The patient’s thorax tomography demonstrated right-sided, irregularly-thickened pleura with nodular masses and invasion of the chest wall into the subcutaneous area. The patient underwent biopsy for a subcutaneous mass in the right anterior chest wall. Pathologic examination revealed a malignant mesenchymal tumor. During follow-up, he suffered from a painful nodule on the scalp and nodules on the fingers, as well as weakness in his right arm. Cranial magnetic resonance imaging illustrated a 1 cm nodule in the left cerebellar hemisphere. Histopathologic examination of the biopsy from the nodule on the scalp revealed a typical mixed type of MPM, with calretinin, vimentin and creatine 5/6 positivity. Distant metastases can be seen in MPM and a biopsy of metastatic regions can yield the diagnosis.

Polymerase chain reaction in the diagnosis of invasive aspergillosis.

In the present study, we present a patient with invasive pulmonary aspergillosis caused by Aspergillus fumigatus diagnosed by polymerase chain reaction (PCR) technique on blood and bronchoalveolar lavage fluid samples of the patient. The value of PCR in the diagnosis of aspergillosis is discussed.

A prospective, multicentre clinical trial comparing cisplatin plus gemcitabine with cisplatin plus etoposide in patients with locally advanced and metastatic non-small cell lung cancer.

Objective:  Cisplatin‐gemcitabine (PG) and cisplatin‐etoposide (PE) combinations are active regimens for non‐small cell lung cancer (NSCLC). The present study aimed to compare PG with PE in the treatment of patients with stage IIIB and IV NSCLC.

Relationship between primary lesion metabolic parameters and clinical stage in lung cancer

OBJECTIVES The relation of PET-derived parameters as maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV) with clinical stage in lung cancer and correlation of SUVmax of primary tumor and that of metastatic lesion was studied in lung cancer patients. MATERIALS AND METHODS Patients with lung cancer who were referred for FDG PET/CT were included in the study. RESULTS PET/CT scans and pathology reports of 168 patients were assessed. A total of 146 (86.9%) of these patients had a diagnosis of non-small cell lung cancer (NSCLC) and 22 (13.1%) had small cell lung cancer (SCLC). Metabolic parameters such as SUVmax, TLG and MTV showed significant differences in all the stages in NSCLC patients (p<0.001). However, after tumors sizes <25 mm were excluded, no significant differences in SUVmax between stages were observed. No significant differences were found between these metabolic parameters and limited or extended disease SCLC. Tumor diameter correlated with primary tumor SUVmax and significant correlations between primary lesion SUVmax and metastatic lesion SUVmax were found. CONCLUSIONS Although differences were found regarding indices between stages of NSCLC cases, SUVmax differences between stages seem to be caused by underestimation of SUVmax in small lesions. Other glucose metabolism indexes such as MTV and TLG show promising results in terms of prognostic stratification. Future studies are needed for better understanding of their contribution to clinical cases.

Polymorphisms in the Aurora-A Gene Is Not Associated with Lung Cancer in the Turkish Population

Lung cancer, a complex neoplasm of lung tissue, is influenced by several environmental and genetic factors which could be changed in each individual. Aurora-A gene is related to mitotic events such as: chromosome instability, cell cycle regulation, spindle formation, and kinetechore-microtubule connections. This centrosomic serine/threonine kinase provides a strong connection between mitotic errors and carcinogenesis. The genomic alterations such as single nucleotide polymorphisms (SNPs) can exist in molecular pathways of lung cancer. Therefore, we evaluated the role of genetic polymorphisms of Aurora-A gene in the lung cancer in the Turkish population. Genotypes of five Aurora-A polymorphisms (F31I, V57I, 6328G/A, P50L, and S104L) were determined in 102 healty controls and 102 new diagnosed lung cancer cases. All samples were genotyped with DNA sequence technique. There were not any genotype variations in P50L, S104L, and 6328G/A polymorphisms. The frequencies of both genotypes F31I and V57I in lung cancer patients were not significantly different from those in controls (p > 0.05). A multivariable logistic regression analysis including patient characteristics, such as age and gender, did not change the results.

Primary large cell neuroendocrine carcinoma : A cause of extracardiac uptake site of Tc99m tetrofosmin

A 37-year-old man was admitted with a 1-month history of cough, dyspnea, sputum, and chest pain. Chest radiography showed bilateral parahilar enlargement (Fig 1). Thorax computed tomography (CT) demonstrated heteregenous lobulated mass measured 13 • 8 cm in the anterior mediast inum adjacent to the main vascular structures. TC-99m Tetrofosmin myocard perfusion scan was performed before mediastinoscopy and pearshaped increased activity accumulation was seen above the heart (Fig 2). Mediastinoscopic biopsy was performed and histopathology revealed primary large cell neuroendocrine carcinoma. The patient was referred for chemotherapy. Sites of Extracardiac TC99m Tetrofosmin Uptake:

Total lesion glycolysis by 18F-FDG PET/CT is independent prognostic factor in patients with advanced non-small cell lung cancer.

To determine whether the primary tumor SUVmax and total lesion glycolysis (TLG) measured on 18F‐FDG PET/CT have prognostic significance in patients with non–small‐cell lung cancer (NSCLC).