Publisher's Synopsis
Lung cancer is one of the most common causes of cancer-related death. While surgery is the standard approach to early stage non-small cell lung cancer (NSCLC), radiotherapy plus or minus chemotherapy represent the main treatment option in locally advanced disease (30% of patients), and chemotherapy remains the only available treatment for those with metastatic disease (50% of patients). Moreover, NSCLC is often found to be intrinsically resistant to both chemo- and radiotherapy at the start of treatment and still, the basis behind treatment resistance, remains a challenge. If one could predict chemotherapy response, based on assessment of biological tumor markers, one could maximize therapeutic benefit while limiting toxicity. This assessment would be ideal if performed at the time of initial bronchoscopy, so that it allows patients the option of pursuing alternative regimens earlier in the course of their treatment. On the other hand, direct real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) using the convex probe endobronchial ultrasound (CP-EBUS) is a relatively new minimally-invasive and accurate technique for preoperative staging of NSCLC patients. Moreover, it was recently concluded that EBUS-guided transbronchial needle aspiration (EBUS-TBNA) has a high sensitivity and specificity compared to computed tomography (CT) and positron emission tomography (PET), and as a single procedure for mediastinal LN staging, it allows tissue diagnosis. Tissues obtained by EBUS-TBNA allow further analyses to be carried out e.g genetic analysis; and may help directing NSCLC patients to molecularely-based different therapies. EBUS-TBNA allows genetic evaluations of tumor cells within the LNs and may provide us with indications for therapy in the near future. The molecular features of NSCLC seem to be of interest. One area of such interest is cell-cycle control. Two major pathways involved in the cellular progression from G0-phase to S-phase include the retinoblastoma protein (pRb), cyclin D1, and p16 cell-cycle pathway and the p53/p21 G1-S checkpoint-arrest pathway. Effective control by the cell cycle checkpoints ensures the repair of damaged DNA before replication and prevents the maintenance of deleterious genetic abnormalities. Therefore, it is not surprising that abnormalities of at least one cell-cycle key control protein, reportedly was among the most commonly altered proteins in NSCLC. Ki-67 is a DNA-binding nuclear protein that is expressed throughout the cell cycle in proliferating cells, but not in quiescent (G0) cells. Many studies have reported the predictive value(s) of one or more of these cell cycle proteins, for chemotherapy response in lung cancer.Metastasis to N2 is the most important prognostic factor in completely resected NSCLC. However, patients with stage IIIA N2-NSCLC represent heterogenous groups, from both the prognostic and therapeutic aspects of view. If one could predict chemotherapy response in patients with stage IIIA-N2-NSC If one could predict chemotherapy response in patients with stage IIIA-N2-NSCLC, based on assessment of the cell cycle markers, using EBUS-TBNA; we could maximize therapeutic benefit while limiting toxicity of chemotherapeutic agents. Therefore, in the current study; we examined the expression of the Rb pathway (pRb, cyclin D1, p16), p53 pathway (p53, p21) proteins and Ki-67 labelling indices (LI), by IHC in mediastinal LN specimens obtained by EBUS-TBNA, in pathologically-proven (p) N2-NSCLCs. We investigated their predictive role(s) for platinum-based chemotherapy response. -Study Objectives; there were two main objectives of this study; 1- To investigate the feasibility of EBUS-TBNA for obtaining nodal tissue samples that can be utilized for immunohistochemical analysis. 2- To stratify, molecularly-based, pN2-NSCLC patients into chemo-responsive and chemo-resistant subgroups who might benefit from chemotherapy-tailorment
