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Analysis of Cell Cycle-related Proteins in Mediastinal Lymph Nodes of N2-NSCLC Patients Obtained by EBUS-TBNA: Relevance to Chemotherapy Response
  1. Sherif Mohamed MD (saawm20{at}yahoo.com)
  1. Department of Thoracic Surgery, Chiba University and Department of Pulmonology, Assiut University, Egypt
    1. Kazuhiro Yasufuku, MD,PhD, FC (kyasufuku{at}faculty.chiba-u.jp)
    1. Department of Thoracic Surgery, Chiba University, Japan
      1. Takahiro Nakajima MD (nakajii{at}fc.med.miyazaki-u.ac.jp)
      1. Department of Thoracic Surgery, Chiba University, Japan
        1. Kenzo Hiroshima, MD, PhD (kenzo{at}faculty.chiba-u.jp)
        1. Department of Diagnostic Pathology,Chiba University, Japan
          1. Rieko Kubo (kathy050959{at}yahoo.co.jp)
          1. Department of Thoracic Surgery, Chiba University, Japan
            1. Akira Iyoda, MD, PhD (aiyoda{at}faculty.chiba-u.jp)
            1. Department of Thoracic Surgery, Chiba University, Japan
              1. Shigetoshi Yoshida, MD, PhD (s-yoshida{at}faculty.chiba-u.jp)
              1. Department of Thoracic Surgery, Chiba University, Japan
                1. Makoto Suzuki, MD, PhD (smakoto{at}faculty.chiba-u.jp)
                1. Department of Thoracic Surgery, Chiba University, Japan
                  1. Yasuo Sekine, MD,PhD (sekine{at}faculty.chiba-u.jp)
                  1. Department of Thoracic Surgery, Chiba University, Japan
                    1. Kiyoshi Shibuya, MD, PhD (shibuya{at}faculty.chiba-u.jp)
                    1. Department of Thoracic Surgery, Chiba University, Japan
                      1. Atef Farouk MD (afaroukeg{at}yahoo.com)
                      1. Department of Pulmonology, Faculty of Medicine, Assiut University, Egypt
                        1. Takehiko Fujisawa, MD, PhD (fujisawat{at}faculty.chiba-u.jp)
                        1. Department of Thoracic Surgery, Chiba University, Japan

                          Abstract

                          Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an accurate tool for lymph node staging of non-small lung cancer (NSCLC). The majority of NSCLC patients require systemic chemotherapy during their treatment, with relatively poor responses. If one could predict chemotherapy response, ideally at the time of initial bronchoscopic examination, one could maximize therapeutic benefit while limiting toxicity. Thus, we aimed to investigate the feasibility of EBUS-TBNA for obtaining tissue samples from mediastinal lymph nodes that can be utilized for immunohistochemical analysis; and to stratify, molecularly-based, pN2-NSCLC patients into chemoresponsive and chemoresistant subgroups who might benefit from chemotherapy-tailorment.

                          Methods: We examined the expression of six cell cycle-related proteins (pRb, cyclin D1, p16INK4A, p53, p21Waf1, Ki-67), in mediastinal lymph node specimens obtained by EBUS-TBNA, by immunohistochemistry in 36 pN2-NSCLC patients. We investigated their predictive role(s) for platinum-based chemotherapy response.

                          Results: Immunostaining was feasible in all studied specimens. Univariate analysis revealed that p53 and p21Waf1 expressions were significantly related to the chemotherapy response (p=0.002, p=0.011, respectively). Multivariate logistic regression analysis revealed that only p53 overexpression was associated with poor response to chemotherapy (p=0.021).

                          Conclusions: These results suggest that EBUS-TBNA is a feasible tool for obtaining mediastinal nodal tissue samples amenable for immunohistochemical analysis. Immunostaining of p53 in EBUS-TBNA guided specimens may be useful in predicting response to chemotherapy in N2-NSCLC patients, and help selection of those patients who might benefit from certain chemotherapeutic strategies.

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