Association between PD-L1 expression with EGFR, ALK, and ROS1 driver oncogene mutations in non-small cell lung cancer.

BACKGROUND: Driver mutations and immunological expressions have gained importance in recent years for targeted therapies and immunotherapies of nonsmall cell lung cancer (NSCLC). AIMS: This study examined the association between PD-L1 expression and ALK, ROS1, and EGFR driver oncogene mutations in patients with NSCLC. MATERIALS AND METHODS: A total of 501 NSCLC patients were included for analysis. Immunohistochemistry was performed with a PD-L1 clone 22c3. EGFR mutations were detected by PCR. ALK and ROS1 rearrangement analysis was performed with FISH. Results: There was a highly statistically significant difference between PD-L1 expression and EGFR mutation. PD-L1 expression was higher in the EGFR wild-type than in mutated EGFR (P = 0.0002). There was no relationship between PD-L1 expression and ALK and ROS1 mutations (P = 0.8899, P = 0.2512, respectively). PD-L1 expression was higher in nonadenocarcinomas (non-AC) than in adenocarcinomas (AC) (P = 0.0438). The ALK rearrangement and EGFR mutations were higher in ACs (P = 0.0073, P = 0.0012, respectively). ALK, ROS1 rearrangements, and EGFR mutations were higher in nonsmokers (P < 0.05). EGFR mutations were detected more frequently in females than males (P = 0.001). There was no relationship between gender and ALK, ROS1, and PD-L1 (P > 0.05). The prevalence of EGFR, ALK, and ROS1 driver mutations in the Turkish population was 9.3%, 5.3%, and 2.4%, respectively. CONCLUSIONS: In conclusion, PD-L1 expression and mutated EGFR status have a highly negative association. PD-L1 expression was higher in EGFR wild-type patients. Therefore, it shows that the opportunity to receive PD-L1-related treatment may be higher in these patients. We think that PD-L1 immunohistochemical evaluation will increase the clinical predictive importance in EGFR wild-type cases.

Established and new treatment roadmaps for pleural mesothelioma: opinions of the Turkish Collaborative Group.

Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant improvements in diagnoses and treatments of many malignancies; however, there are still therapeutic challenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncologists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.

An Adolescent Presented With Hemoptysis: Pulmonary Artery Aneurysm in Pediatric Behçet's Disease.

Behçet's disease (BD) is a rare autoimmune and chronic inflammatory vasculitis, characterized by relapsing episodes of oral aphthous and genital ulcers, skin lesions, ocular lesions and vascular involvement. Pulmonary artery involvement is rare in BD but it carries a high mortality risk. In this article, we report a 15-year-old male patient presented with a two-month history of hemoptysis, cough, fewer and weight loss. On physical examination, auscultation revealed decreased breath sounds at left lung base. Bronchoscopy showed narrowed left lower lobe bronchus due to the external compression. Computed tomography angiography revealed multiple bilateral pulmonary artery aneurysms. Pathergy test was positive and he was diagnosed with BD. BD should be considered in the differential diagnosis of childhood hemoptysis.

Characterization of stem-like cells directly isolated from freshly resected laryngeal squamous cell carcinoma specimens.

Larynx cancer (LCa) is an aggressive malignancy, which is the second most common malignant neoplasm of head and neck squamous cell carcinoma. Its incidences have been reported to increase and therapeutic options mostly fail to give positive clinical response especially for the advanced LCa cases. In this study we aimed to isolate stem-like cells from freshly resected LCa tumor specimens and characterize them by quantitative real time PCR (qRT-PCR) for expression of cancer stem cell markers including SOX2, OCT4, KLF4, ABCG2, CXCR4 and CD44. Our results showed that CD133(high) cells directly isolated from freshly resected tumor specimens exhibit elevated levels of SOX2, OCT4 and KLF4, and have increased expression levels of ABCG2 and CXCR4, which were associated with resistance of tumors to regular chemotherapeutic reagents. In conclusion, this study offers a useful approach utilizing CD133 to isolate stem cells directly from fresh tissues, which gives the opportunity to develop novel therapeutic tools specifically targeting these cells through their further characterization.

Pleomorphic Carcinoma of the Lung with High Serum Beta-human Chorionic Gonadotropin Level and Gynecomastia

Although gynecomastia is a well-defined paraneoplastic syndrome in patients with non-small cell lung cancer, the association with pleomorphic carcinoma has not been reported. A 50-yr-old man presented with bilateral gynecomastia and elevated serum beta-human chorionic gonadotropin (beta hCG) level. Chest tomography showed a mass in the right middle lobe. Right middle lobectomy and mediastinal lymph node dissection were performed. beta hCG levels decreased rapidly after surgery. Histological examination revealed pleomorphic carcinoma with positive immunostaining for beta hCG. Serum beta hCG levels began to increase gradually on postoperatively 4th month. Computed tomography detected recurrence and chemotherapy was started. After second cycle of chemotherapy, beta hCG levels decreased dramatically again and tomography showed regression in mass. Patient died 6 months later due to brain metastasis. beta hCG expression may be associated with aggressive clinical course and increased risk of recurrence, also beta hCG levels may be used to evaluate therapy response in patients with pleomorphic carcinoma.

MMP-2, TIMP-2 and CD44v6 expression in non-small-cell lung carcinomas

<p><b>INTRODUCTION</b>Factors that emerge as crucial participants in tumour invasion and metastases are matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinase (TIMP) inhibitors and cellular adhesion molecules (CD44 and similar molecules). They play important roles in tumour invasion and metastasis in non-small-cell lung carcinomas (NSCLCs).</p><p><b>MATERIALS AND METHODS</b>The study was performed using the data of 33 patients. MMP-2 from the metalloproteinase family, TIMP-2 from the metalloproteinase inhibitor family and the adhesion molecule CD44v6 expression were investigated immunohistochemically to search their role in the metastasis and the clinical outcome of the patients with NSCLCs.</p><p><b>RESULTS</b>Twenty-three tumours (70%) were squamous cell carcinoma (SCC), 9 (27%) were adenocarcinoma (AC), and 1 (3%) was large cell carcinoma (LCC). MMP-2 and TIMP-2 were expressed in high rates in NSCLC but CD44v6 expression was about 50%. Lymphatic invasion was less frequent in TIMP-2- positive patients and this difference was statistically significant (P = 0.005). There was a statistically significant difference between SCCs and ACs with respect to CD44v6 tumoral expression (P = 0.004). Also, there was a negative correlation between lymphatic invasion and the extent of CD44v6; lymphatic invasion was significantly less in CD44v6-positive cases (P = 0.013).</p><p><b>CONCLUSION</b>We found that TIMP-2 and CD44v6 can decrease the lymphatic invasion in NSCLCs. Also there was observed histiotype-related pattern of CD44v6 variant expression in SCCs.</p>