机构地区:[1]山东省耳鼻喉医院头颈外科,济南250023 [2]山东省耳鼻喉医院病理科,济南250023 [3]山东省耳鼻喉医院头颈放疗科,济南250023 [4]山东省耳鼻喉医院影像科,济南250023
出 处:《中华医学杂志》2024年第26期2417-2423,共7页National Medical Journal of China
摘 要:目的观察局部晚期下咽癌患者术前同步放化疗后肿瘤退缩的病理学特点及放化疗抵抗相关分子标志物的表达水平变化。方法回顾性分析2016年8月至2020年8月山东省耳鼻喉医院头颈外科44例行术前同步放化疗的局部晚期下咽癌患者临床资料。所有患者先行同步放化疗,放化疗结束后行电子喉镜及影像学检查评估肿瘤退缩状况,4周后进行手术治疗,术后对原发灶标本进行连续病理大切片处理,HE染色及脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法检测残存癌灶的分布特点和凋亡情况,免疫组化检测残存癌灶的增殖情况及放化疗抵抗相关分子标志物信号传导与转录激活因子3(STAT3)、低氧诱导因子1α(HIF-1α)、性别决定区Y框蛋白2(SOX2)、p53的表达水平。结果共纳入44例患者,均为男性,年龄(58.3±3.5)岁。其中梨状窝癌40例,下咽后壁癌4例;T3期29例,T4期15例;Ⅲ期6例,Ⅳ期38例。44例患者同步放化疗后根据实体瘤疗效评价标准(RECIST)原发部位达到完全缓解(CR)13例,部分缓解(PR)22例,疾病稳定(SD)9例。原发灶切除方式包括下咽环周切除19例,全喉部分下咽切除2例;环状软骨上次全喉切除环舌固定术23例。22例PR患者中,大PR(缓解率≥70%)10例,小PR(缓解率<70%)12例。所有原发灶切除患者术后病理大切片HE染色发现残存癌灶的患者30例(68.2%);其中CR患者中3例检测到残存癌灶(3/13),均为局部癌灶残留;大PR患者中6例检测到残存癌灶(6/10),4例为散在分布,2例为局部癌灶残留;小PR及SD患者均检测到大片残存癌灶。TUNEL法对有残存癌灶的30例标本进行检测均未发现凋亡现象且Ki-67的阳性表达率均<10%。放化疗抵抗相关分子标志物检测发现残存癌灶中19例(63.3%)STAT3(3.40±2.49比5.23±3.02,t=-2.932,P=0.007)及22例(73.3%)HIF-1α(3.73±2.66比6.97±3.05,t=-4.45,P<0.001)表达量高于放化疗前,其余分子标志物在放化疗前后�Objective To investigate the pathological characteristics of tumor regression and the expression level of chemoradiotherapy resistance-related molecular markers after preoperative concurrent radiochemotherapy in patients with locally advanced hypopharyngeal carcinoma.Methods The clinical data of 44 patients with locally advanced hypopharyngeal carcinoma who underwent preoperative concurrent radiochemotherapy in the Department of Head and Neck Surgery of Shandong Otolaryngology Hospital from August 2016 to August 2020 were retrospectively analyzed.All patients received preoperative concurrent chemotherapy and radiotherapy.After radiochemotherapy,electronic laryngoscopy and imaging examination were performed to assess the tumor regression status.After 4 weeks,surgical resection was performed,and the specimens of the primary focus were processed as continuous pathological sections.After operation,HE staining and TdT-mediated dUTP nick-end labeling(TUNEL)method were used to detect the distribution characteristics and apoptosis of the remaining cancer focus,and immunohistochemistry was performed to determine the proliferation of the remaining cancer focus and the expression of radiation resistance-related molecular markers[signal transducer and activator of transcription 3(STAT3),hypoxia-inducible factor-1alpha(HIF-1α),sex determining region Y-box 2(SOX2),and P53].Results A total of 44 patients were included,all of whom were male,with a mean age of(58.3±3.5)years.There were 40 cases of pyriform sinus carcinoma and 4 cases of posterior pharyngeal wall carcinoma.Twenty-nine cases were in stage T3 and 15 cases were in stage T4.There were 6 stageⅢcases and 38 stageⅣcases.According to the response evaluation criteria in solid tumors(RECIST),13 patients achieved complete response(CR),22 patients had partial response(PR),and 9 patients achieved stable disease(SD)after concurrent radiochemotherapy.The primary lesion resection methods included 19 cases of hypopharyngeal circumferential resection and 2 cases of total lary
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