Chovanec Martin, Smetana Karel, Betka Jan, Plzák Jan, Brabec Jirí, Moya-Alvarez Violeta, André Sabine, Kodet Roman, Gabius Hans-Joachim
1st Faculty of Medicine, Institute of Anatomy, Charles University, Prague, Czech Republic.
Int J Oncol. 2005 Aug;27(2):409-15.
This study represents a combined lectin and immuno-histochemical analysis of normal, dysplastic and malignant squamous epithelia of the upper aerodigestive tract with emphasis on the relation between lectin reactivity and the cells' proliferative/anti-apoptotic potential. Staining by double-labeling to detect pKi67, DeltaNp63alpha, alpha2,3/6-linked sialic acid (NeuNAc) and galectin-3-reactive epitopes was performed on specimens of 8 normal cases, 27 primary tumours and 15 regional lymph node metastases. Normal epithelia expressed alpha2,6-linked NeuNAc in the basal layer, while alpha2,3-linked NeuNAc was observed in suprabasal layers. In normal epithelium pKi67 and DeltaNp63alpha positivity was seen in the basal layer and galectin-3-reactive sites in suprabasal layers. The studied squamous cell carcinomas and their metastases showed a tendency for stratification but with markedly altered architecture. The expression of the studied markers was heterogeneous between the different cancer cases but comparable between the corresponding primary and secondary lesions. Glycophenotypic properties were correlated with the level of differentiation. Tumour cell populations were characterized by occurrence of the p63+/pKi67+ alpha2,3-NeuNAc+ alpha2,6-NeuNAc+ phenotype. Analysis of the expression patterns of pKi67, p63 and galectin-3-reactive epitopes (Gal-3-RE) delineated statistically significant interrelationships (Gal-3-RE vs. p63: r = -0.709; Gal-3-RE vs. pKi67: r = -0.623; pKi67 vs. p63: r = 0.895). Of the studied markers only Gal-3-RE expression was correlated to the differentiation-dependent grading (G1 vs. G2: p = 0.007, G2 vs. G3: p = 0.006, G1 vs. G3: p = 0.002). DeltaNp63alpha expression was statistically different only between G1 and G3 (p = 0.03). No statistically significant differences were detected between the primary tumours and the corresponding regional lymph node metastases. Based on the concept of the sugar code further analysis of cell characteristics such as proliferation together with lectin histochemical features, especially using tissue lectins as probes, is thus warranted.
本研究采用凝集素和免疫组织化学联合分析方法，对上下呼吸道和消化道的正常、发育异常及恶性鳞状上皮进行研究，重点关注凝集素反应性与细胞增殖/抗凋亡潜能之间的关系。对8例正常病例、27例原发性肿瘤和15例区域淋巴结转移灶的标本进行双重标记染色，以检测pKi67、DeltaNp63alpha、α2,3/6-连接唾液酸（NeuNAc）和半乳糖凝集素-3反应性表位。正常上皮在基底层表达α2,6-连接的NeuNAc，而在基底层以上各层观察到α2,3-连接的NeuNAc。在正常上皮中，pKi67和DeltaNp63alpha阳性见于基底层，半乳糖凝集素-3反应位点见于基底层以上各层。所研究的鳞状细胞癌及其转移灶显示出分层倾向，但结构明显改变。所研究标记物的表达在不同癌症病例之间存在异质性，但在相应的原发和继发病变之间具有可比性。糖表型特性与分化程度相关。肿瘤细胞群体的特征是出现p63+/pKi67+α2,3-NeuNAc+α2,6-NeuNAc+表型。对pKi67、p63和半乳糖凝集素-3反应性表位（Gal-3-RE）表达模式的分析表明，它们之间存在统计学上的显著相关性（Gal-3-RE与p63：r = -0.709；Gal-3-RE与pKi67：r = -0.623；pKi67与p63：r = 0.895）。在所研究的标记物中，只有Gal-3-RE的表达与依赖分化的分级相关（G1与G2：p = 0.007，G2与G3：p = 0.006，G1与G3：p = 0.002）。DeltaNp63alpha的表达仅在G1和G3之间存在统计学差异（p = 0.03）。在原发性肿瘤和相应的区域淋巴结转移灶之间未检测到统计学上的显著差异。基于糖代码的概念，因此有必要进一步分析细胞特征，如增殖以及凝集素组织化学特征，特别是使用组织凝集素作为探针。
