Imbalance between proliferation and apoptosis may be responsible for treatment failure after postoperative radiotherapy in squamous cell carcinoma of the oropharynx
Imbalance between proliferation and apoptosis may be responsible for treatment failure after postoperative radiotherapy in squamous cell carcinoma of the oropharynx
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DOI：
10.1016/s1368-8375(03)00005-8
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发表时间：
2003-07-01
期刊：
影响因子：
4.8
通讯作者：
Distel, L
中科院分区：
文献类型：
--
作者：
Grabenbauer, GG;Suckorada, O;Distel, L
探讨细胞凋亡、细胞增殖及临床因素对口咽鳞癌根治术后放疗的预后价值。在1985年至1995年期间，共有82名患者的84个肿瘤进入研究。原发性肿瘤42例（50%）累及扁桃体，23例（27%）累及软腭，19例（23%）累及舌根。中位年龄为52岁（范围：36-73岁）。pT和pN类别（UICC 1997）为：T1（24）、T2（36）、T3（18）、T4（6）、NO（31）、N1（12）、N2（38）、NX（8）。所有患者在初次手术中均获得了组织学上清晰的边缘。术后放射治疗60戈伊，分6周进行，每日2戈伊。用单克隆抗体MIB 1免疫组化法检测细胞核Ki-67标记指数（LI）的表达，用末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记法（TUNEL）检测凋亡细胞。中位随访时间为43个月（范围：14-132个月）。5年时的总生存率、无病生存率和局部肿瘤控制率分别为59%、70%和76%。凋亡指数和Ki-67标记的中值分别为1.6%（范围0-4.7%）和20%（范围0-79%）。与凋亡和增殖之间平衡的所有其他患者（5年无病生存率：66- 86%，P=0.003）相比，凋亡指数小于或等于1.6%与更高的增殖率（5年无病生存率：26%）相关时，具有深刻的负面影响。无病生存期的其他重要预后因素包括：肿瘤部位（扁桃体：83% vs软腭：66% vs舌根：49%，P=0.02），RT持续时间（≤ 47天：83% vs >47天：55%，P=0.03），Ki-67 LI（≤ 20%：84% vs >20%：56%，P=0.006）。RT持续时间（P=0.01）、肿瘤部位（P=0.02）和Ki-67 LI（P= 0.02）对局部区域控制有显著的预后影响。与具有较高凋亡指数的患者（70- 80%，P=0.009）相比，低凋亡指数与较高增殖率一起导致低至25%的不利的局部控制。凋亡指数和增殖之间的不平衡，可能会发现鳞状细胞癌患者在手术后局部复发和术后RT的高风险。这些因素在临床试验中的前瞻性观察是必要的，以进一步阐明这一现象。(C)2003爱思唯尔科技有限公司版权所有。
To assess the prognostic value of apoptosis, proliferation and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). Between 1985 and 1995, a total of 82 patients with 84 tumors were entered onto the study. Forty-two primary tumors (50%) involved the tonsils, 23 (27%) the soft palate, and 19 (23%) the base of the tongue. Median age was 52 years (range, 36-73 years). The pT- and pN-categories (UICC 1997) were: T1 (24), T2 (36), T3 (18), T4 (6), NO (31), N1 (12), N2 (38), NX (8). Histologically clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given with 60 Gy in 6 weeks and single daily fractions of 2 Gy. The expression of the nuclear Ki-67 labeling index (LI) was investigated by immunostaining using the monoclonal antibody MIB 1 and apoptotic carcinoma cells were identified using the terminal deoxynucleotidyltransferase-(TdT)-mediated dUTP nick end labeling (TUNEL) technique. Median follow-up was 43 months (range, 14-132 months). Overall survival, disease-free survival, and locoregional tumor control rates were 59, 70 and 76% at 5 years. Median values for apoptotic index and Ki-67 labeling were 1.6% (range 0-4.7%), and 20% (range, 0-79%), respectively. Apoptotic index less than or equal to1.6% had a profound negative impact when associated with higher proliferation rates (5-year disease-free survival: 26%) as compared to all other patients with a balance between apoptosis and proliferation (5-year disease-free survival: 66-86%, P=0.003). Additional significant prognostic factors for disease-free survival were: tumor site (tonsils: 83% vs soft palate: 66% vs base of tongue: 49%, P=0.02), duration of RT (less than or equal to47 days: 83% vs >47 days: 55%, P=0.03), Ki-67 LI (less than or equal to20%: 84% vs >20%: 56%, P=0.006). A significant prognostic impact on locoregional control was noted for the duration of RT (P=0.01), tumor site (P=0.02), and the Ki-67 LI (P=0.02). A low apoptotic index together with higher proliferation rates led to unfavourable local control as low as 25% compared to the patients with higher apoptotic index (70-80%, P=0.009). An imbalance between apoptotic index and proliferation may identify patients with squamous cell carcinoma at high risk for local recurrence after surgery and postoperative RT. Prospective observation of these factors in clinical trials is warranted to further elucidate this phenomenon. (C) 2003 Elsevier Science Ltd. All rights reserved.