Unidad AECC de Investigación Traslacional en Cáncer, Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA), Murcia, Spain.
Grupo Cirugía Experimental, CIBERehd, Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA), IMIB-Arrixaca, Murcia, Spain.
Transl Res. 2015 Aug;166(2):196-206. doi: 10.1016/j.trsl.2015.02.006. Epub 2015 Feb 28.
The identification of tumor cells in lymph nodes is essential for the correct classification of patients with colorectal cancer who may benefit from adjuvant treatments. Proper classification of tumor stage becomes entangled by variables such as an insufficient number of lymph nodes examined, which can result in erroneous or missed diagnosis. The determination of pathologic factors in the primary tumor associated with positive lymph nodes is an area of research that has attempted to provide variables to solve this problem. In the present study, we observed that the localization of annexin A2 (AnxA2) in a cell membrane is the characteristic that distinguishes tumor cells with high invasiveness. Localization of AnxA2 expression was also studied in tissue specimens from 58 patients with invasive colorectal carcinoma (T3-T4), who had undergone colectomy with radical lymph node dissection. Interestingly, the membrane pattern observed in tumor cell lines was also identified in patient's tissue samples and allowed us to distinguish among different cell populations with the tumor. Univariate analysis showed that tumor deposits in pericolic fat, extramural vascular invasion, and amount of cells with AnxA2 membrane pattern in the tumor invasive edge had a significant influence on lymph node metastasis. On the contrary, multivariate analysis revealed that the number of cells with AnxA2 membrane pattern (P < 0.05) and tumor deposits (P < 0.05) was significantly associated with lymph node metastasis. Furthermore, AnxA2 cellular localization was observed in cell clusters that define tumor budding, and a significant association between both variables was detected.
在淋巴结中识别肿瘤细胞对于正确分类可能受益于辅助治疗的结直肠癌患者至关重要。肿瘤分期的正确分类受到诸如检查的淋巴结数量不足等变量的困扰，这可能导致错误或漏诊。与阳性淋巴结相关的原发性肿瘤的病理因素的确定是一个试图提供变量来解决此问题的研究领域。在本研究中，我们观察到膜定位的膜联蛋白 A2（AnxA2）是区分高侵袭性肿瘤细胞的特征。还研究了 58 例接受根治性淋巴结清扫术的侵袭性结直肠癌（T3-T4）患者的组织标本中 AnxA2 表达的定位。有趣的是，在肿瘤细胞系中观察到的膜模式也在患者的组织样本中得到了鉴定，并使我们能够区分肿瘤中的不同细胞群体。单因素分析表明，肿瘤在结肠旁脂肪中的沉积物、壁外血管侵犯以及肿瘤侵袭边缘中具有 AnxA2 膜模式的细胞数量对淋巴结转移有显著影响。相反，多因素分析显示，具有 AnxA2 膜模式的细胞数量（P<0.05）和肿瘤沉积物（P<0.05）与淋巴结转移显著相关。此外，在定义肿瘤芽生的细胞簇中观察到 AnxA2 细胞定位，并检测到这两个变量之间存在显著关联。
