Menon Anand G, Fleuren Gert Jan, Alphenaar Ellen A, Jonges Liesbeth E, Janssen van Rhijn Connie M, Ensink N Geeske, Putter Hein, Tollenaar Rob A E M, van de Velde Cornelis J H, Kuppen Peter J K
Department of Surgery, K6-R, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Cancer Immunol Immunother. 2003 Feb;52(2):121-6. doi: 10.1007/s00262-002-0363-6. Epub 2003 Jan 30.
Epithelial tumours consist of an epithelial compartment and a stromal compartment, which are sometimes separated by a basal membrane-like structure. We sought to determine whether these factors have prognostic value in 84 curatively resected stage II and III colorectal cancer by immunohistochemically staining tumours for leucocytes (CD45) and extracellular matrix, and to assess the presence of a basal membrane-like structure. Leucocyte infiltration was also assessed in hematoxylin-eosin (HE) stained sections. Most leucocytes were located in the tumour stroma. A relatively high intraepithelial leucocyte infiltration was significantly correlated with a lower level of tumour recurrence (P=0.03) and a longer disease-free survival (P=0.05), whereas leucocytes located in the tumour stroma (P=0.92) or at the advancing margin (p=0.06) were not. Intraepithelial leucocyte infiltration was also significantly correlated with leucocyte infiltration in the tumour stroma (P=0.02) and at the advancing tumour margin (P=0.005), and as assessed in HE-stained tumour sections (P=0.05), but each of these parameters on its own did not have a prognostic value in predicting disease-free survival. Moreover, the presence of a basal membrane-like structure surrounding the tumour epithelium was inversely correlated with the number of intraepithelial leucocytes (P=0.05), suggesting that this membrane-like structure functions as a barrier to intraepithelial leucocyte infiltration. We conclude that leucocytes must be in the direct vicinity of tumour cells to affect tumour growth. The presence of an extracellular matrix barrier seems to prevent this interaction.
上皮性肿瘤由上皮成分和间质成分组成,二者有时被类似基底膜的结构分隔开。我们试图通过对84例经根治性切除的Ⅱ期和Ⅲ期结直肠癌肿瘤进行白细胞(CD45)和细胞外基质的免疫组化染色,来确定这些因素是否具有预后价值,并评估是否存在类似基底膜的结构。还在苏木精-伊红(HE)染色切片中评估白细胞浸润情况。大多数白细胞位于肿瘤间质中。上皮内白细胞浸润相对较高与较低的肿瘤复发水平(P = 0.03)和较长的无病生存期(P = 0.05)显著相关,而位于肿瘤间质(P = 0.92)或肿瘤进展边缘(P = 0.06)的白细胞则无此相关性。上皮内白细胞浸润也与肿瘤间质(P = 0.02)和肿瘤进展边缘(P = 0.005)的白细胞浸润显著相关,并且在HE染色的肿瘤切片中评估时也显著相关(P = 0.05),但这些参数单独来看在预测无病生存期方面均无预后价值。此外,肿瘤上皮周围类似基底膜结构的存在与上皮内白细胞数量呈负相关(P = 0.05),这表明这种膜状结构起到了上皮内白细胞浸润屏障的作用。我们得出结论,白细胞必须直接靠近肿瘤细胞才能影响肿瘤生长。细胞外基质屏障的存在似乎阻止了这种相互作用。