Background: A debate has been ongoing whether non-small cell lung cancer(NSCLC) with neuroendocrine(NE) differentiation likely indicates malignant behavior, poor prognosis, and sensitivity to chemotherapy. In response to this issue, we retrospectively investigated NE differentiation in NSCLC patients who underwent anatomical pulmonary surgery.
Methods: A total of 274 patients who met the inclusion criteria through January 2000 to December 2008 were enrolled in this study because they had the detailed material and enough paraffin tumor samples for tissue microarray. The recommended antibody panel consisted of CgA, Syn, NCAM, Leu-7, PGP9.5, and MAP-2. We also counted Ki-67 in the tissues to present the nuclear proliferation index. The Kaplan-Meier estimator and the Cox proportional hazard model multivariate analysis were applied to observe the relationship between NE differentiation and postoperative survival of the patients.
Results: The Cox analysis of different NE score combinations on the prognosis of NSCLC after surgical treatment did not reach statistical significance (score 1, score 2, and score≥3 vs score 0, P=0.527; score 0 vs score ≥1, P=0.791; score<2 vs score≥2, P=0.163; score<3 vs score≥3, P=0.293). The Kaplan-Meier estimator did not give significant difference in the survival of NE score combinations in each pTNM layer. In the perioperative chemotherapy group, we also did not find a positive correlation for the survival analysis of NE score combinations (score 1, score 2, and score≥3 vs score 0, P=0.692; score 0 vs score≥1, P=0.922; score<2 vs score ≥2, P=0.264; score<3 vs score≥3, P=0.484).
Conclusions: The NE differentiation of NSCLC reflects some structure and functional characteristics of NELT, although it cannot be used as an independent factor of biological behavior and survival for NSCLC patients who underwent surgery in our group.
背景与目的: 非小细胞肺癌（Non-small cell lung cancer, NSCLC）中的神经内分泌（Neuroendocrine, NE）分化是否是恶性生物学行为与不良预后的指标，是否对化疗更敏感一直是人们关注与争论的问题。通过对NSCLC术后标本进行有关NE分化的回顾性研究，比较NE分化与NSCLC患者生存的关系，以探讨NSCLC中NE分化的临床意义。
方法: 按入组标准共收集274例肺癌临床资料及标本，将标本制作成组织芯片，行CgA、Syn、NCAM、Leu-7、PGP9.5和MAP-2等NE抗体染色，同时行Ki-67染色了解核增殖指数。通过不同的评分组合分析NE分化对NSCLC的预后意义。
结果: 不同NE评分对经手术治疗的NSCLC预后的影响均未达到统计学差异（1分、2分、≥3分vs 0分，P=0.527；0分vs ≥1分，P=0.791； < 2分vs≥2分，P=0.163； < 3分vs≥3分，P=0.293）。进一步将pTNM分期按Ⅰ期、Ⅱ期与Ⅲ期进行分层，单因素分析NE评分在各层对预后的影响，显示差异无统计学意义。围手术期化疗组不同NE评分同预后的比较无阳性结果（1分、2分、≥3分vs0分，P=0.692；0分vs≥1分，P=0.922； < 2分vs≥2分，P=0.264； < 3分vs≥3分，P=0.484）。
结论: NE分化体现了部分NSCLC具有NELT结构、功能上的特点，本组研究显示NE分化同NSCLC预后无关，并非其高恶性度的指标。