Semino-Mora Cristina, Liu Hui, McAvoy Thomas, Nieroda Carol, Studeman Kimberley, Sardi Armando, Dubois Andre
Laboratory of Gastrointestinal and Liver Studies, Department of Medicine, Uniformed Services University and United States Military Cancer Institute, Bethesda, MD 20814, USA.
Ann Surg Oncol. 2008 May;15(5):1414-23. doi: 10.1245/s10434-007-9778-9. Epub 2008 Feb 26.
Pseudomyxoma peritonei (PMP) is characterized by peritoneal tumors arising from a perforated appendiceal adenoma or adenocarcinoma, but associated entry of enteric bacteria in the peritoneum has not been considered as a cofactor. Because Gram-negative organisms can upregulate MUC2 mucin gene expression, we determined whether bacteria were detectable in PMP tissues.
In situ hybridization was performed on resection specimens from five control subjects with noninflamed, nonperforated, non-neoplastic appendix and 16 patients with PMP [six with disseminated peritoneal adenomucinosis (DPAM) and 10 with peritoneal mucinous carcinomatosis (PMCA)]. Specific probes were designed to recognize: (1) 16S rRNA common to multiple bacteria or specific to H. pylori; (2) H. pylori cagA virulence gene; or (3) MUC2 or MUC5AC apomucins. Specimens from one patient with PMCA were examined by ultrastructural immunohistochemistry. Bacterial density and apomucin expression were determined in four histopathological compartments (epithelia, inflammatory cells, stroma, and free mucus).
Enteric bacteria were detected in all specimens. Bacterial density and MUC2 expression were significantly (p < 0.05) higher in PMCA than in DPAM and controls and were highest in free mucin. MUC2 was also expressed in dysplastic epithelia and in associated inflammatory cells. MUC2 expression was significantly correlated with bacterial density.
Multiple enteric bacteria are present in PMP, and bacterial density and MUC2 expression is highest in the malignant form of PMP. Based on these observations, we propose that the bacteria observed in PMP may play a role in the mucinous ascites and perhaps promote carcinogenesis.
腹膜假黏液瘤（PMP）的特征是由穿孔性阑尾腺瘤或腺癌引起的腹膜肿瘤，但肠细菌进入腹膜尚未被视为一个辅助因素。由于革兰氏阴性菌可上调MUC2黏蛋白基因表达，我们确定PMP组织中是否可检测到细菌。
对5例非炎症、非穿孔、非肿瘤性阑尾的对照受试者以及16例PMP患者[6例弥漫性腹膜腺黏液瘤（DPAM）和10例腹膜黏液性癌（PMCA）]的切除标本进行原位杂交。设计特异性探针以识别：（1）多种细菌共有的16S rRNA或幽门螺杆菌特异性的16S rRNA；（2）幽门螺杆菌cagA毒力基因；或（3）MUC2或MUC5AC脱辅基黏蛋白。对1例PMCA患者的标本进行超微结构免疫组织化学检查。在四个组织病理学区域（上皮、炎性细胞、基质和游离黏液）中测定细菌密度和脱辅基黏蛋白表达。
所有标本中均检测到肠细菌。PMCA中的细菌密度和MUC2表达显著高于DPAM和对照（p<0.05），且在游离黏液中最高。MUC2也在发育异常上皮和相关炎性细胞中表达。MUC2表达与细菌密度显著相关。
PMP中存在多种肠细菌，且在PMP的恶性形式中细菌密度和MUC2表达最高。基于这些观察结果，我们提出在PMP中观察到的细菌可能在黏液性腹水中起作用，并且可能促进癌变。
