诱导化疗后进展期声门上喉癌切缘及分子标志物研究

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、＞10mm的外科切缘更有利于肿瘤退缩后的切缘安全。

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

Abstract: Objective To investigate the clinical significance of molecular biomarker (eIF4E, survivin, cyclin D1 andP27) 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 LSCCwere 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, wereunderwent partial laryngectomy. These patients were divided into three groups according to the shortest margin distances: <5mm (Margin 1) group (n=14), 5-10 mm (Margin 2) group (n=17) and ＞10 mm (Margin 3) group (n=28). Tumors and theadjacent 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 necrosisand tumor retraction after chemotherapy. In Margin 1 group, the retraction zone was found in 10 cases (10/14), necrotic anddegenerative tumor cells were occasionally found. No retraction zone was found in Margin 2 and Margin 3 groups. Theexpressions of eIF4E and survivin proteins were higher in primary tumors. The positive expression rates of eIF4E andsurvivin proteins decreased sharply with the increase of the margin in three groups. There were no significant differences inpositive expressions of cyclin D1 and P27 between three groups. In 59 patients with laryngeal cancer, 12 (20.3%) recurred 3years 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 mmand no expression of markers are relatively safe.