淋巴结微转移与微乳头成分的关系及其对Ⅰ期肺腺癌患者预后的影响

This study aimed to investigate the relationship between lymph node micrometastasis and histologic patterns of adenocarcinoma, with a particular focus on their joint effect on prognosis. We retrospectively reviewed 235 patients with stage I adenocarcinoma from January 2009 to December 2009. Lymph node micrometastasis was evaluated by immunohistochemical staining for cytokeratin (AE1/AE3) and thyroid transcription factor-1. A logistic regression model was applied to confirm the predictive factors of micrometastasis. Survival analysis was performed to evaluate the effect of micrometastasis on prognosis. Lymph node micrometastasis was observed in 35 patients (15%). Patients with micrometastasis had significantly worse recurrence-free survival (P<0.001) and overall survival (P<0.001) compared with those without micrometastasis. Micropapillary component was confirmed as an independent predictor of increased frequency of micrometastasis (P<0.001). Among 62 patients with adenocarcinoma with a micropapillary component, 23 (37%) had lymph node micrometastasis. Micropapillary-positive/micrometastasis-positive patients had significantly worse survival compared with micropapillary-positive/micrometastasis-negative patients (RFS, P=0.039; OS, P=0.002) and micropapillary-negative patients (recurrence-free survival, P<0.001; overall survival, P<0.001). Moreover, the presence of micrometastasis correlated with a higher risk of locoregional recurrence (P=0.031) rather than distant recurrence (P=0.456) in micropapillary-positive patients. In summary, lymph node micrometastasis was more frequently observed in adenocarcinoma with a micropapillary component. Moreover, lymph node micrometastasis could provide helpful prognostic information in patients with resected stage I lung adenocarcinoma with a micropapillary component; thus, immunohistochemical detection of micrometastatic tumor cells in lymph nodes should be recommended.

根治性手术切除后的I期肺腺癌患者有20%-30%的5年复发率。2011年IASLC/ATS/ERS的肺腺癌新分类提出了5种不同生物学行为和预后的腺癌亚型(贴壁、乳头、腺管、微乳头和实性),可有效预测患者的术后复发和远期生存。此外,隐匿性的淋巴结微转移是另一个导致术后复发的可能因素。

WHO肺肿瘤组织学分类(2015版)给予淋巴结微转移具体的定义:即转移灶小于0.2 mm。目前淋巴结微转移是否被认作为转移,及对患者预后的影响仍存争议。来自上海市肺科医院的陈昶研究团队试图明确腺癌不同亚型与淋巴结微转移的相关性,并明确其预后价值,相关结果发表在American Journal of Surgical Pathology上。

研究纳入术后病理诊断为I期的浸润性肺腺癌患者235例,共3,314个淋巴结样本。腺癌成分根据新分类进行诊断,明确主要成分以及次要成分。用角蛋白(CK)[细胞膜染色]和甲状腺转录因子1(TTF-1)[细胞核染色]免疫组化染色的方法检测淋巴结中的微转移灶。

研究结果发现,35例(15%)患者被检出淋巴结微转移。按阳性淋巴结个数分层,26例有1个淋巴结阳性,9例有2个淋巴结阳性;按淋巴结站数分层,15例N1阳性,20例N2阳性。

(单个细胞型淋巴结微转移:A, CK染色; B, TTF-1; 细胞簇型淋巴结微转移:C, CK染色; D, TTF-1)(注:连续切片,CK、TTF-1双阳性则定义为微转移阳性)

生存分析发现,淋巴结微转移与患者较差的RFS (P < 0.001)和OS (P < 0.001)有关。多因素分析也进一步明确,淋巴结微转移是I期肺腺癌患者预后更差的独立危险因素(RFS: P = 0.002, HR = 2.22, 95% CI, 1.26-3.92; OS: P = 0.004, HR = 2.70, 95% CI, 1.37-5.33)。

Logistic回归分析发现,腺癌中含有微乳头成分(P < 0.001, OR = 7.10, 95% CI, 2.92-17.28)是淋巴结微转移的独立预测因素。进一步亚组分析含有微乳头成分的患者共62例,其中存在淋巴结微转移的患者23例(37%)。

生存分析发现,淋巴结微转移与患者较差的RFS (P = 0.039)和OS (P = 0.002)有关。多因素分析也进一步明确,淋巴结微转移是其预后更差的独立危险因素(RFS: P = 0.002, HR = 2.92, 95% CI, 1.35-6.31; OS: P = 0.003, HR = 3.87, 95% CI, 1.57-9.53)。

淋巴结微转移与肺腺癌的微乳头成分存在着密切的相关性,并与患者的预后密切相关。对于常规淋巴结HE染色阴性且病灶含有微乳头成分的I期肺腺癌患者,可进一步采用免疫组化方法的来检测淋巴结微转移的情况,从而获得更准确的预后信息。

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