Aubert Sébastien, Berdelou Amandine, Gnemmi Viviane, Behal Hélène, Caiazzo Robert, D'herbomez Michèle, Pigny Pascal, Wemeau Jean Louis, Carnaille Bruno, Renaud Florence, Bouchindhomme Brigitte, Leteurtre Emmanuelle, Perrais Michael, Pattou François, Do Cao Christine
Institut de Pathologie, Centre de Biologie Pathologie, CHRU de Lille, 59037, Lille, France.
Faculté de Médecine, Université de Lille, 59045, Lille, France.
Virchows Arch. 2018 Mar;472(3):461-468. doi: 10.1007/s00428-018-2303-7. Epub 2018 Feb 1.
Lymph node involvement (LNI) is one of the most important prognostic factors for poor survival in medullary thyroid carcinoma (MTC). At diagnosis, LNI is found in over 50% of sporadic MTCs, and especially in large tumours. Cervical lymph node dissection is therefore mandatory during MTC surgery. However, some large tumours (responsible for high preoperative basal calcitonin levels) are found to lack LNI, and can be cured definitely. Preoperative detection of these particular tumours might spare patients from undergoing extensive cervical dissection. The objective of the present retrospective study of a series of large sporadic MTCs was to identify clinical, biological and pathological factors that were predictive of LNI. Consecutive cases of large, sporadic MTCs (measuring at least 1 cm in diameter) were retrieved and reviewed. The levels of several mature microRNAs (miRs) in paraffin-embedded samples were assessed using qPCR. Of the 54 MTCs, 26 had LNI and 28 were pN0. Relative to pN0 patients, patients with LNI had a significant higher preoperative basal calcitonin level (p = 0.0074) and a greater prevalence of infiltrative margins (p < 0.0001), lymphovascular invasion (p = 0.0004), extrathyroidal extension (p < 0.0001), a higher pT stage (p = 0.0003) and more abundant desmoplastic stroma (p = 0.0006). Tumour expression levels of miR-21 (p = 0.0008) and miR-183 (p = 0.0096) were higher in the LNI group. The abundance of desmoplastic stroma (p = 0.007) and the miR-21 expression level (p = 0.0026) were independent prognostic factors for LNI. The abundance of desmoplastic stroma and high levels of miR-21 expression were strong indicators of LNI, and may thus help the surgeon to choose the extent of cervical lymph node dissection for large, sporadic MTCs with no preoperatively obvious LNI.
淋巴结受累（LNI）是甲状腺髓样癌（MTC）患者生存预后不良的最重要因素之一。在确诊时，超过50%的散发性MTC患者存在LNI，尤其是在肿瘤较大的患者中。因此，MTC手术期间必须进行颈部淋巴结清扫。然而，一些导致术前基础降钙素水平升高的大肿瘤却未发现LNI，且可被彻底治愈。术前检测这些特殊肿瘤可能使患者免于接受广泛的颈部清扫。本项针对一系列大型散发性MTC的回顾性研究的目的是确定预测LNI的临床、生物学和病理学因素。收集并回顾了连续的大型散发性MTC病例（直径至少1厘米）。使用qPCR评估石蜡包埋样本中几种成熟微小RNA（miR）的水平。在54例MTC中，26例存在LNI，28例为pN0。与pN0患者相比，LNI患者术前基础降钙素水平显著更高（p = 0.0074），浸润性边缘的发生率更高（p < 0.0001），存在淋巴管侵犯（p = 0.0004）、甲状腺外侵犯（p < 0.0001），pT分期更高（p = 0.0003），促纤维增生性间质更丰富（p = 0.0006）。LNI组中miR-21（p = 0.0008）和miR-183（p = 0.0096）的肿瘤表达水平更高。促纤维增生性间质的丰富程度（p = 0.007）和miR-21表达水平（p = 0.0026）是LNI的独立预后因素。促纤维增生性间质的丰富程度和高水平的miR-21表达是LNI的有力指标，因此可能有助于外科医生为术前无明显LNI的大型散发性MTC选择颈部淋巴结清扫的范围。
