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Aims: Human papilloma virus (HPV)‐independent cervical adenocarcinoma (CA) is usually diagnosed at an advanced stage, while the therapeutic options are limited. Therefore, effective treatment options are required. The programmed cell death 1 (PD‐1) inhibitor pembrolizumab has been approved for the treatment of patients with recurrent or metastatic cervical squamous cell carcinoma expressing PD‐ligand 1 (PD‐L1). However, no data regarding PD‐L1 expression in HPV‐independent CA are available. Thus, we evaluated the association between PD‐L1 expression and the clinicopathological characteristics and survival of patients with HPV‐independent CA. Methods: We evaluated PD‐L1, mismatch repair (MMR) protein expression and the immune stromal features of 44 patients with HPV‐independent CA. PD‐L1 expression was defined as a combined positive score (CPS) ≥1 and a tumour proportion score (TPS) ≥1%. Results: PD‐L1 expression was observed in 14 cases (31.8%) with CPS ≥1 and 12 cases (27.3%) with TPS ≥1%. PD‐L1 expression, based on either the CPS or the TPS, was associated with a high tumour‐infiltrating lymphocyte percentage (CPS = P < 0.001; TPS = P < 0.001). Patients with a PD‐L1 CPS ≥1 showed worse progression‐free survival and overall survival than PD‐L1‐negative patients (P = 0.004 and P = 0.023, respectively). Forty‐two cases demonstrated intact MMR expression and two cases demonstrated loss of MSH2/MSH6. Conclusions: Our data demonstrated that PD‐L1 was expressed in HPV‐independent CA, especially in clear cell carcinoma, and that PD‐L1 expression is a negative prognostic marker. Our data support the role of PD‐L1 in HPV‐independent CA and its potential as an immunotherapeutic target. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Despite significant advances in its research of tumor biology and therapy, the prognosis for this neoplasm has still remained poor. The great majority of anticancer agents, regardless of their mechanisms of action, exert their lethal actions on cancer cells by inducing apoptosis following drug-induced cellular damage. Many reported studies have evaluated the prognostic and therapeutic implications of apoptosis in lung cancer, but their exact clinical value has remained unclear. Therefore more prospective studies are currently required to further validate apoptosis as prognostic and predictive biomarkers in lung cancer patients. The current study reviewed the studies on the prognostic and predictive significances of Bcl-2 family proteins in NSCLC. We also discussed potential treatment strategies which could target apoptotic proteins in lung carcinoma cells. Exception for Bcl-2 itself, studies of the prognostic significance of other Bcl-2 family proteins is markedly limited. The abundance of literature suggests that targeting apoptosis in NSCLC is feasible. However, many troubling questions arise with the use of new drugs or treatment strategies, and new biomarkers are needed. [ABSTRACT FROM AUTHOR]

BACKGROUND Activating mutations in the epidermal growth factor receptor ( EGFR) in non-small cell lung carcinoma (NSCLC) are associated significantly with responsiveness to EGFR tyrosine kinase inhibitors. The objective of this study was to investigate the suitability of cytologic specimens for assessing EGFR mutations in lung adenocarcinomas. METHODS Sixty paired histologic and cytologic specimens of lung adenocarcinoma were collected. Exons 18 through 21 of the EGFR gene were amplified using polymerase chain reaction, and the mutation status of each sample was analyzed by pyrosequencing. A comparison of EGFR mutation status between histologic specimens and cytologic specimens was performed. RESULTS The overall EGFR mutation concordance rate between histologic specimens and corresponding cytologic specimens was 91.7%. No significant difference was observed in the concordance rate between cytologic specimens from primary lesions and specimens from metastatic lesions ( P = .63). The following parameters were correlated with the most reliable EGFR mutation results using the pyrosequencing method (100% concordance with the corresponding histologic specimens) in cytologic samples: a DNA concentration >25 ng/μL, content of >30 tumor cells, or a tumor percentage >30%. CONCLUSIONS In this study, routinely prepared cytologic specimens were reliable sources for assessing EGFR mutation status. The authors concluded that cytologic specimens from metastatic lesions and primary tumors are suitable for the successful assessment of EGFR mutation status. Cancer (Cancer Cytopathol) 2013;121:311-9. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Aims: The anaplastic lymphoma kinase gene ( ALK) has attracted considerable attention as a potential molecular target in non-small-cell lung cancer (NSCLC). However, it is unclear whether ALK alterations are acquired during the metastatic progression of NSCLC. Methods and results: ALK status and ALK expression were evaluated in a series of 67 primary NSCLCs and their corresponding metastatic lesions using fluorescence in-situ hybridization and immunohistochemistry. ALK rearrangement was detected in 7.5% (5/67) of the primary tumours and in 9.0% (6/67) of the metastases ( P < 0.001). ALK copy number gain (CNG) was detected in 1.5% (1/67) of the primary tumours and in 35.8% (24/67) of the metastases. Whereas ALK rearrangement was detected only in adenocarcinomas, CNG was identified in various histological subtypes of NSCLC. ALK expression was detected in 11.9% (8/67) of the primary tumours and in 25.4% (17/67) of the metastatic lesions. Conclusions: ALK alteration and ALK expression can be acquired during metastatic progression in NSCLC, and ALK CNG is associated with ALK expression. [ABSTRACT FROM AUTHOR]