Abstract
Necrosis and apoptosis represent two pathogenetically distinct types of cell death. Necrosis is associated with pathologic conditions while apoptosis is a physiological process of programmed cell death, which is associated with normal tissue growth and is frequently impaired in various forms of cancer. Tumor necrosis and apoptotic index (AI) have been previously evaluated as prognostic biomarkers in lung cancer, but their exact clinical value remains unclear. The aim of this study was to perform a systematic review of the MEDLINE literature on the prognostic significance of these histopathological markers in patients with non-small cell lung carcinoma (NSCLC). Although a substantial body of evidence suggests that tumor necrosis may be a strong predictor of aggressive tumor behavior and reduced survival in patients with NSCLC, the independent prognostic value of this biomarker remains to be firmly established. Furthermore, previous data on the prognostic significance of apoptotic index in NSCLC are relatively limited and largely controversial. More prospective studies are necessary in order to further validate tumor necrosis and AI as prognostic markers in NSCLC.
Highlights
Lung cancer remains the leading cause of death from cancer worldwide and one of the 10 leading causes of death from all causes (Murray & Lopez 2013)
Conclusions several previous clinicopathological studies have demonstrated that tumor necrosis may be associated with an aggressive tumor behavior and reduced survival of patients, the independent prognostic significance of this biomarker in non-small cell lung carcinoma (NSCLC) has not been firmly established yet
These previous results should be interpreted with caution and viewed in light of certain limitations, mainly including the small sample size and retrospective nature of most series, the variable distribution of the clinicopathological and treatment characteristics of the studied populations as well as the discrepancy in the criteria used by different research groups to define the presence and extent of microscopically recognized necrotic tissue
Summary
Lung cancer remains the leading cause of death from cancer worldwide and one of the 10 leading causes of death from all causes (Murray & Lopez 2013). Apoptosis is a physiological phenomenon that occurs spontaneously and is associated with normal tissue growth It is an active process, linked to specific molecular pathways (Edinger & Thompson 2004). Severely injured cells without causing an inflammatory host reaction Factors such as hypoxia, irradiation or chemotherapeutic agents can cause irreversible DNA damage and activate the apoptotic process, diminishing the risk of a possibly harmful mutation and malignant transformation (Kumar et al 2007). The prognostic significance of tumor necrosis and apoptotic index (AI) in NSCLC has been previously investigated in several clinicopathological studies spanning the past three decades. Most of these previous reports have yielded variable or even controversial results. In the last decades, the prognostic significance of necrosis in resectable non-small cell carcinomas has been assessed by many investigators in a series of, mostly retrospective, studies investigating the impact of these histological features on survival of patients.
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