Macia Ivan, Aiza Gemma, Ramos Ricard, Escobar Ignacio, Rivas Francisco, Ureña Anna, Aso Samantha, Rosado Gabriela, Rodriguez-Taboada Pau, Deniz Carlos, Nadal Ernest, Capella Gabriel
Thoracic Surgery Department, Hospital Universitari de Bellvitge; Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) and Unit of Human Anatomy and Embryology, Department of Pathology and Experimental Therapeutics, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Translational Research Laboratory, Catalan Institute of Oncology and IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
J Invest Surg. 2022 Feb;35(2):315-324. doi: 10.1080/08941939.2020.1857479. Epub 2020 Dec 21.
The relapse rate in non-small cell lung cancer (NSCLC) is high, even in localized disease, suggesting that the current approach to pathological staging is insufficiently sensitive to detect occult micrometastases present in resected lymph nodes. Therefore, we aimed to determine the prognostic value of the expression of embryonic molecular markers in histologically-negative lymph nodes of completely-resected NSCLC.
76 completely-resected NSCLC patients were included: 60 pN0 and 16 pN1. Primary tumors and 347 lymph node were studied. CEACAM5, FGFR2b, and PTPN11 expression levels were evaluated through mRNA analysis using real-time RT-qPCR assay. Statistical analyses included the Kruskal-Wallis test, Kaplan Meier curves, and log-rank tests.
CEACAM5 expression levels were scored as high in of 90 lymph nodes (26%). The molecular-positive lymph nodes lead to the restaging of 37 (62%) pN0 patients as molecular N1 or N2 and 5 (31%) pN1 cases were reclassified as molecular-positive N2. Surprisingly, molecular-positive patients associated with a better OS (overall survival, p = 0,04). FGFR2b overexpression was observed in 41 (12%) lymph nodes leading to the restaging of 17 patients (22%). Again a trend was observed toward a better DFS (disease-free survival) in the restaged patients (p = 0,09). Accordingly, high expression levels of CEACAM5 or FGFR2b in the primary were related to better DFS (p = 0,06; p < 0,02, respectively).
Molecular nodal restaging based on expression levels of CEACAM5 and/or FGFR2b, does not add relevant clinical information to pathological staging of NSCLC likely related to the better prognosis of their overexpression in primary tumors.
非小细胞肺癌(NSCLC)的复发率很高,即使是局限性疾病,这表明当前的病理分期方法对检测切除淋巴结中存在的隐匿微转移敏感性不足。因此,我们旨在确定胚胎分子标志物在完全切除的NSCLC组织学阴性淋巴结中的表达的预后价值。
纳入76例完全切除的NSCLC患者:60例pN0和16例pN1。研究了原发性肿瘤和347个淋巴结。通过实时RT-qPCR分析,使用mRNA分析评估CEACAM5、FGFR2b和PTPN11的表达水平。统计分析包括Kruskal-Wallis检验、Kaplan Meier曲线和对数秩检验。
90个淋巴结(26%)的CEACAM5表达水平被评为高。分子阳性淋巴结导致37例(62%)pN0患者重新分期为分子N1或N2,5例(31%)pN1病例重新分类为分子阳性N2。令人惊讶的是,分子阳性患者的总生存期(OS)更好(p = 0.04)。在41个(12%)淋巴结中观察到FGFR2b过表达,导致17例患者(22%)重新分期。在重新分期的患者中再次观察到无病生存期(DFS)有更好的趋势(p = 0.09)。因此,原发性肿瘤中CEACAM5或FGFR2b的高表达与更好的DFS相关(分别为p = 0.06;p < 0.02)。
基于CEACAM5和/或FGFR2b表达水平的分子淋巴结重新分期,可能与原发性肿瘤中其过表达的更好预后相关,并未为NSCLC的病理分期增加相关临床信息。