Carico Elisabetta, Fulciniti Franco, Giovagnoli Maria Rosaria, Losito Nunzia Simona, Botti Gerardo, Benincasa Giulio, Farnetano Maria Giuseppina, Vecchione Aldo
U.O. Citopatologia, IIa Facoltà Medicina e Chirurgia La Sapienza, Rome, Italy.
Virchows Arch. 2009 Sep;455(3):245-51. doi: 10.1007/s00428-009-0811-1. Epub 2009 Aug 13.
An immunohistochemical (IHC) study has been conducted on 34 cases of untreated endocervical adenocarcinomas collected among three institutions (Ospedale S. Andrea, Rome; Istituto Nazionale Tumori "Fondazione G. Pascale", Naples; and Clinica Malzoni, Avellino). The E-cadherin and alpha- and beta-catenin complex status has been investigated along with p16INK4a in all studied cases with the aim to study whether the pattern of expression of the cadherin-catenin complex could be causally related to the expression of P16INK4a protein. Results were evaluated for statistical significance by a non-parametric test (Kruskal-Wallis). Endocervical adenocarcinomas as a group were uniformly expressing p16INK4a except for two cases, and all lesions displayed downregulation of the cadherin-catenin complex, without demonstrating statistically significant differences among the different histotypes. The lack of nuclear accumulation of beta-catenin found in this group of lesions probably implies that no alteration of the beta-catenin/Wnt metabolic pathway is present in endocervical adenocarcinoma, as opposed to what is found in the literature for squamous carcinoma of the cervix. The diffuse expression of p16INK4a protein in this group of neoplasms stresses the important role of high-risk human papillomavirus infection in neoplastic causation possibly via the viral E7-mediated inactivation of pRB tumor-suppressor protein and also underlines the useful role of p16INK4a immunostaining in the diagnostic algorithm of endocervical adenocarcinomas. In consideration of these findings, investigation of downstream beta-catenin genes c-myc and cyclin D1 is sought as possibly contributive in the molecular pathogenesis of endocervical adenocarcinoma.
对来自三个机构（罗马的圣安德烈亚医院、那不勒斯的国家肿瘤研究所“G. 帕斯卡尔基金会”和阿韦利诺的马尔佐尼诊所）收集的34例未经治疗的宫颈管腺癌进行了免疫组织化学（IHC）研究。在所有研究病例中，对E-钙黏蛋白、α-连环蛋白和β-连环蛋白复合物状态以及p16INK4a进行了研究，目的是探讨钙黏蛋白-连环蛋白复合物的表达模式是否可能与P16INK4a蛋白的表达存在因果关系。通过非参数检验（Kruskal-Wallis）对结果进行统计学意义评估。除两例外，宫颈管腺癌组均一致表达p16INK4a，所有病变均显示钙黏蛋白-连环蛋白复合物下调，不同组织学类型之间未显示出统计学显著差异。在这组病变中发现β-连环蛋白缺乏核积聚，这可能意味着宫颈管腺癌中不存在β-连环蛋白/Wnt代谢途径的改变，这与文献中关于宫颈鳞状癌的情况相反。该组肿瘤中p16INK4a蛋白的弥漫性表达强调了高危人乳头瘤病毒感染在肿瘤发生中的重要作用，可能是通过病毒E7介导的pRB肿瘤抑制蛋白失活，同时也强调了p16INK4a免疫染色在宫颈管腺癌诊断算法中的有用作用。考虑到这些发现，寻求对下游β-连环蛋白基因c-myc和细胞周期蛋白D1的研究，其可能对宫颈管腺癌的分子发病机制有贡献。
