天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (5): 533-537.doi: 10.11958/20181997

• 临床研究 • 上一篇    下一篇

诱导化疗后进展期声门上喉癌切缘及分子标志物研究

张文超 1，张强 1，岳玖玲 1，卓姗姗 1，潘毅 2，张仑 1   

  1. 基金项目：天津市卫生局科技基金计划项目（2011kz75） 作者单位：1天津医科大学肿瘤医院颌面-耳鼻喉科，国家肿瘤临床医学研究中心，天津市“肿瘤防治”重点实验室（邮编300060），2病理科 作者简介：张文超（1974），男，博士，副主任医师，主要从事头颈部肿瘤外科及基础研究
  • 收稿日期:2018-12-12 修回日期:2019-03-26 出版日期:2019-05-15 发布日期:2019-05-15
  • 通讯作者: 张文超 E-mail:zwbeyond_999@sina.com
  • 基金资助:
    天津市卫生局科技基金计划项目

Study on the molecular surgical margin of patients with locally advanced supraglottic laryngeal carcinoma after induction chemotherapy

ZHANG Wen-chao1, ZHANG Qiang1, YUE Jiu-ling1, ZHUO Shan-shan1, PAN Yi2, ZHANG Lun1   

  1. 1 Department of Maxilla Facial & ENT, 2 Department of Pathology, Tianjin Medical University Cancer & Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
  • Received:2018-12-12 Revised:2019-03-26 Published:2019-05-15 Online:2019-05-15
  • Contact: ZHANG WEN CHAO E-mail:zwbeyond_999@sina.com

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摘要： 摘要：目的 探讨行诱导化疗后的进展期声门上喉癌退缩后不同距离最短切缘组分子标志物表达差异及其在 手术定界中的意义。方法 收集2011年5月—2014年11月在天津医科大学肿瘤医院头颈科治疗的95例进展期声 门上喉癌（T3～4，N0～2，M0）患者的临床资料，行多西他赛＋顺铂＋5-氟尿嘧啶（TPF）方案诱导化疗；选择其中59 例疾病稳定（SD）及部分缓解（PR）患者中强烈要求手术者行部分喉切除术，按距肿瘤最短切缘分为<5 mm（Margin 1） 组14例、5~10 mm（Margin 2）组17例及＞10 mm组（Margin 3）28例。标本制成组织芯片，采用常规病理及高通量免疫 组化技术检测eIF4E、survivin、cyclinD1、P27这4种肿瘤标志物的表达，并比较不同切缘组3年喉内局部复发率。结 果 原发瘤（T）可见化疗后坏死及肿瘤退缩；Margin 1组切缘10例含有肿瘤退缩区（10/14），偶可见坏死变性的瘤细 胞；Margin 2、Margin 3切缘组均未见肿瘤退缩区。eIF4E、survivin在原发瘤T高表达，3个切缘组的阳性表达率随切缘 增大急剧下降。各组cyclinD1、P27的阳性表达率差异均无统计学意义。59例喉癌患者术后3年复发12例（20.3%）， 其中Margin 1组11例（78.6%），Margin 2组1例（5.9%），Margin 3组0例，Margin 1组明显高于Margin 2和Margin 3组 （P＜0.05）。结论 eIF4E、survivin可能作为诱导化疗后声门上喉癌切缘的比较敏感的标志物，标志物无表达、＞10 mm的外科切缘更有利于肿瘤退缩后的切缘安全。

关键词: 喉肿瘤, 诱导化疗, 声门上喉癌, 喉部分切除, 分子切缘, 肿瘤退缩区

Abstract: Abstract: Objective To investigate the clinical significance of molecular biomarker (eIF4E, survivin, cyclin D1 and P27) expressions in defining the surgical margin in local advanced supraglottic laryngeal squamous cell carcinoma (LSCC) after induction chemotherapy. Methods A total of 95 patients with local advanced (T3-4, N0-2, M0) supraglottic LSCC were enrolled in this study. Clinical response was evaluated after induction chemotherapy with a TPF (docetaxel/ cisplatin/ fluorouracil) regimen. Fifty-nine patients with stable disease (SD) and partial remission (PR) and requiring surgery, were underwent partial laryngectomy. These patients were divided into three groups according to the shortest margin distances: <5 mm (Margin 1) group (n=14), 5-10 mm (Margin 2) group (n=17) and ＞10 mm (Margin 3) group (n=28). Tumors and the adjacent tissues were prepared for tissue microarray (TMA) and were used to identify the expressions of eIF4E, survivin, cyclin D1 and P27. The recurrence rates in three years were also analyzed. Results Primary tumors (T) showed necrosis and tumor retraction after chemotherapy. In Margin 1 group, the retraction zone was found in 10 cases (10/14), necrotic and degenerative tumor cells were occasionally found. No retraction zone was found in Margin 2 and Margin 3 groups. The expressions of eIF4E and survivin proteins were higher in primary tumors. The positive expression rates of eIF4E and survivin proteins decreased sharply with the increase of the margin in three groups. There were no significant differences in positive expressions of cyclin D1 and P27 between three groups. In 59 patients with laryngeal cancer, 12 (20.3%) recurred 3 years after operation, including 11 (78.6%) in Margin 1 group, 1 (5.9%) in Margin 2 group and 0 (5.9%) in Margin 3 group. The recurrence rate was significantly higher in Margin 1 group than that in Margin 2 and Margin 3 groups (P＜0.05). Conclusion The eIF4E and survivin proteins might be used as more sensitive molecular margin markers of partial laryngectomy after induction chemotherapy in patients with local advanced supraglottic LSCC. The margin beyond 10 mm and no expression of markers are relatively safe.

Key words: laryngeal neoplasms, induction chemotherapy, supraglottic laryngeal carcinoma, partial laryngectomy, molecular margins, tumor regression area