Lo Muzio L, Pannone G, Mignogna M D, Staibano S, Mariggiò M A, Rubini C, Procaccini M, Dolci M, Bufo P, De Rosa G, Piattelli A
Institute of Dental Sciences, University of Ancona, Ancona, Italy.
Histol Histopathol. 2004 Oct;19(4):1089-99. doi: 10.14670/HH-19.1089.
P-cadherin, a transmembrane molecule similar to E-cadherin involved in the cell-cell adhesion, and catenins form complexes between its cytoplasmic domain and the cytoskeleton. Five cell lines, 108 specimens of oral squamous cell carcinomas (OSCC), 9 metastasis and 10 of normal oral mucosa were examined to evaluate P-cadherin expression and cellular localization by immunohistochemistry and western-blotting. In normal oral mucosa there was a membranous expression only in basal and parabasal layers. 91 cases (84%) showed membranous/cytoplasmic positivity, whereas 17 cases (16%) were negative. In particular, while well-differentiated carcinomas showed P-cadherin upregulation, the protein was homogeneously hypo- or unexpressed in low-differentiated carcinomas. There was a statistically significant correlation between P-cadherin expression and tumour grading: G3 tumours had a lower score than G1-G2 tumours (P<0.05). When analysed for prognostic significance, patients with no P-cadherin expression (score 0) had poorer overall and diseases-free survival rates than the P-cadherin-expressing group (score 1) (P=0.0463 and P=0.0471, respectively). Western blotting analysis of cell lines and tissue samples confirmed immunohistochemical findings. When cell staining pattern of positive cases was examined, 52 cases showed a prevalent membranous pattern, while 39 had a prevalent cytoplasmic pattern. Cases with prevalent cytoplasmic staining showed high rates of lymph node metastases (P>0.05), and regional relapse (P <0.05) and poorer survival rates than the group with prevalent membranous expression (P<0.0001). An absent P-cadherin expression could constitute a hallmark of aggressive biological behaviour in oral squamous cell carcinoma.
P-钙黏蛋白是一种与参与细胞间黏附的E-钙黏蛋白类似的跨膜分子，连环蛋白在其胞质结构域与细胞骨架之间形成复合物。通过免疫组织化学和蛋白质印迹法检测了5种细胞系、108例口腔鳞状细胞癌（OSCC）标本、9例转移灶及10例正常口腔黏膜标本，以评估P-钙黏蛋白的表达及细胞定位。在正常口腔黏膜中，仅在基底层和副基底层有膜性表达。91例（84%）表现为膜性/胞质阳性，而17例（16%）为阴性。特别是，高分化癌显示P-钙黏蛋白上调，而在低分化癌中该蛋白均匀低表达或无表达。P-钙黏蛋白表达与肿瘤分级之间存在统计学显著相关性：G3级肿瘤的评分低于G1-G2级肿瘤（P<0.05）。在分析其预后意义时，无P-钙黏蛋白表达（评分0）的患者的总生存率和无病生存率均低于P-钙黏蛋白表达组（评分1）（分别为P=0.0463和P=0.0471）。细胞系和组织样本的蛋白质印迹分析证实了免疫组织化学结果。在检查阳性病例的细胞染色模式时，52例表现为主要为膜性模式，而39例主要为胞质模式。主要为胞质染色的病例的淋巴结转移率（P>0.05）、区域复发率（P<0.05）较高，且生存率低于主要为膜性表达的组（P<0.0001）。P-钙黏蛋白表达缺失可能是口腔鳞状细胞癌侵袭性生物学行为的一个标志。
