GTSP1 expression in non-smoker and non-drinker patients with squamous cell carcinoma of the head and neck

IntroductionThe main risk factors for head and neck squamous cell carcinoma (HNSCC) are tobacco and alcohol consumption and human papillomavirus (HPV) infection. However, in a subset of patients, no risk factors can be identified. Glutathione S-transferase π (GTSP1) is a carcinogen-detoxifying enzyme that is activated by exposure to carcinogens, and it is associated with a reduction in response to toxic therapies. We studied the expression of GTSP1 in tumor and non-tumor tissue samples from patients with and without these risks to identify whether GTSP1 expression differs according to exposure to carcinogens.Materials and methodsNon-smoker/non-drinker (NSND) and smoker/drinker (SD) patients were matched according to age, gender, tumor site, TNM stage, grade and histological variants to establish 47 pairs of patients who have been previously tested for HPV. GTSP1 immunostaining was analyzed using a semi-quantitative method with scores ranging from 0 to 3 according to the area of immunostaining.ResultsGTSP1 expression was detected in the tumors of both groups. GTSP1 expression was higher in the non-tumor margins of SD patients (p = 0.004). There was no association between GTSP1 expression and positivity for HPV. No differences in survival were observed according to GTSP1 staining in tumors and non-tumor margins.ConclusionThis study showed that GTSP1 was expressed in tumors of HNSCC patients regardless of smoking, drinking or HPV infection status. The difference in GTSP1 expression in non-tumor margins between the two groups may have been due to two possible reasons. First, elevated GTSP1 expression in SD patients might be the result of activation of GTSP1 in response to exposure to carcinogens. Second, alternatively, impairment in the detoxifying system of GTSP1, as observed by the reduced expression of GTSP1, might make patients susceptible to carcinogens other than tobacco and alcohol, which may be the underlying mechanism of carcinogenesis in the absence of risk factors.引言 头颈部鳞状细胞癌（head and neck squamous cell carcinoma, HNSCC）的主要危险因素为烟草与酒精暴露以及人乳头瘤病毒（human papillomavirus, HPV）感染。然而，部分患者无法检出明确的危险因素。谷胱甘肽S-转移酶π（Glutathione S-transferase π, GTSP1）是一种可经致癌物暴露激活的致癌物解毒酶，其表达水平与毒性治疗应答降低相关。本研究通过检测携带/不携带上述危险因素的患者的肿瘤与非肿瘤组织样本中GTSP1的表达水平，探究GTSP1的表达是否因致癌物暴露情况而异。 材料与方法 本研究按照年龄、性别、肿瘤部位、TNM分期、肿瘤分级及组织学亚型，对非吸烟非饮酒（non-smoker/non-drinker, NSND）患者与吸烟饮酒（smoker/drinker, SD）患者进行配对，最终纳入47例此前已完成HPV检测的患者对。采用半定量法对GTSP1免疫染色结果进行分析，根据免疫染色面积将评分设为0~3分。 结果 两组患者的肿瘤组织中均检测到GTSP1表达。吸烟饮酒患者的非肿瘤切缘组织中GTSP1表达水平更高（p = 0.004）。GTSP1表达与HPV感染阳性无显著关联。无论肿瘤组织还是非肿瘤切缘组织的GTSP1染色情况，均未观察到生存率存在差异。 结论 本研究证实，无论吸烟、饮酒状态以及HPV感染情况如何，头颈部鳞状细胞癌患者的肿瘤组织中均存在GTSP1表达。两组患者非肿瘤切缘组织中GTSP1表达的差异可能源于两种潜在机制：其一，吸烟饮酒患者GTSP1表达升高，可能是其在致癌物暴露下GTSP1被激活的结果；其二，若如前所述GTSP1表达降低，则提示其解毒系统功能受损，可能使患者对烟草与酒精以外的致癌物易感，这或许是无明确危险因素患者的潜在致癌机制。