Tai Shyh-Kuan, Lee Janet I, Ang K Kian, El-Naggar Adel K, Hassan Khaled A, Liu Diane, Lee J Jack, Ren Hening, Hong Waun K, Mao Li
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2004 Aug 15;10(16):5554-7. doi: 10.1158/1078-0432.CCR-04-0208.
Abnormalities of FHIT, a candidate tumor suppressor gene, have frequently been found in multiple malignancies, including head and neck squamous cell carcinoma (HNSCC). To define its role in HNSCC treated with surgery and postoperative radiotherapy (PORT), the Fhit protein expression status was investigated in 80 patients enrolled in a prospective Phase III clinical trial addressing the dose and fractionation regimen of PORT.
Immunohistochemical staining of HNSCC tissue sections for Fhit expression was performed. The Fhit expression status was correlated with the clinicopathological characteristics and clinical course. The median follow-up duration was 4.9 years.
Loss of Fhit expression was found in 52 of the 80 study patients (65%). There was not a significant association between Fhit expression and clinical characteristics. Patients whose tumor exhibited negative Fhit expression had a significantly worse 5-year overall survival duration [hazard ratio = 0.49; 95% confidence interval, 0.23-1.03; P = 0.05 (log-rank test)] than did those whose tumor exhibited positive Fhit expression. One third of the patients with a Fhit-negative tumor had distant metastasis during the follow-up period. Paradoxically, patients classified as high risk who had a Fhit-negative tumor experienced locoregional recurrence less often (18%) than did high-risk patients who had a Fhit-positive tumor (33%).
Loss of Fhit expression is a poor prognostic indicator in patients with HNSCC. However, tumors lacking Fhit expression may be more sensitive to PORT and therefore more susceptible to locoregional control.
FHIT作为一种候选肿瘤抑制基因，其异常在包括头颈部鳞状细胞癌（HNSCC）在内的多种恶性肿瘤中经常被发现。为了明确其在接受手术及术后放疗（PORT）的HNSCC中的作用，我们在一项针对PORT剂量和分割方案的前瞻性III期临床试验的80例患者中研究了Fhit蛋白表达状态。
对HNSCC组织切片进行Fhit表达的免疫组织化学染色。将Fhit表达状态与临床病理特征及临床病程相关联。中位随访时间为4.9年。
80例研究患者中有52例（65%）出现Fhit表达缺失。Fhit表达与临床特征之间无显著关联。肿瘤Fhit表达为阴性的患者5年总生存时间显著更差[风险比=0.49；95%置信区间，0.23 - 1.03；P = 0.05（对数秩检验）]，而肿瘤Fhit表达为阳性的患者则不然。Fhit阴性肿瘤患者中有三分之一在随访期间发生远处转移。矛盾的是，被归类为高危的Fhit阴性肿瘤患者局部区域复发的发生率（18%）低于Fhit阳性肿瘤的高危患者（33%）。
Fhit表达缺失是HNSCC患者预后不良的指标。然而，缺乏Fhit表达的肿瘤可能对PORT更敏感，因此更易受到局部区域控制。
