NRF2在不同分化程度浸润性非黏液型肺腺癌中的表达及意义

NRF2 expression in invasive non-mucinous lung adenocarcinoma and its clinicopathological significance

目的探讨NRF2在不同分化程度浸润性非黏液型肺腺癌(invasive non-mucinous adenocarcinomas,INMA)同病理亚型中的表达差异,及其与淋巴结转移和预后的相关性。方法收集同济大学附属上海市肺科医院2017年11月至2018年6月手术的498例INMA病例,分析HE切片中不同亚型占比并采用免疫组织化学法检测各亚型中NRF2的分布情况;按分化程度分组分析NRF2与淋巴结转移、预后的相关性。结果INMA组织学亚型之间NRF2表达存在差异,在实性型、微乳头型及复杂腺体型中表达水平最高(n=331,H-score平均值226.73±83.357),在腺泡型及乳头型中表达水平次之(n=332,H-score平均值141.74±92.893),在贴壁生长型中表达水平最弱(n=197,H-score平均值58.48±75.753)。NRF2在高级别亚型中呈现高表达趋势,与INMA患者淋巴结转移、分化程度、TNM分期相关(P<0.001),在低分化组中NRF2阳性与淋巴结转移(P=0.005)具有相关性;NRF2阳性是患者发生复发转移事件的独立危险因素(P<0.001)。结论NRF2在INMA不同组织学亚型中表达差异明显,NRF2阳性与淋巴结转移及预后不良相关。

Objective To investigate the expression of NRF2 in different pathological subtypes of invasive non-mucinous lung adenocarcinoma(INMA)and its clinicopathological significance.Methods A total of 498 patients with INMA admitted in Shanghai Pulmonary Hospital from November 2017 to January 2018 were enrolled.The surgical specimen were pathologically examined with HE staining and the expression of NRF2 was detected with immunohistochemistry.The relationship between NRF2 expression and lymph node metastasis and prognosis of patients was analyzed.Results There were significant differences in the expression levels of NRF2 among different histological subtypes of INMA,the solid,micro papillary and complex gland subtypes had the highest expression of NRF2(n=331,H-score:226.73±83.357),followed by acinar and papillary subtypes(n=332,H-score:141.74±92.893),and the expression level was the weakest in the lepidic subtype(n=197,H-score:58.48±75.753).The expression of NRF2 was correlated with lymph node metastasis,differentiation degree and TNM stage(all P<0.001).Subgroup analysis showed that high NRF2 expression in the poorly differentiated subgroup was associated with lymph node metastasis(P=0.005).NRF2 was an independent risk factor for recurrence and metastasis in INMA patients.Conclusion The expression level of NRF2 is significantly different in different histological subtypes of INMA;the positive NRF2 expression is related to lymph node metastasis and poor prognosis.