Walsh S V, Loda M, Torres C M, Antonioli D, Odze R D
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Am J Surg Pathol. 1999 Aug;23(8):963-9. doi: 10.1097/00000478-199908000-00015.
In patients with chronic ulcerative colitis (CUC), polypoid dysplastic lesions (PDLs) are morphologically similar to sporadic adenomas (SAs), but may be biologically distinct from them and are managed differently. p53 mutations have been shown to occur at an earlier phase in the progression of CUC-associated neoplasia when compared with sporadic colon carcinogenesis. In contrast, APC gene mutations are common and occur at an earlier stage in the development of SA. beta catenin is a cell membrane protein that accumulates in the nucleus of colon cancer cells in response to APC gene mutations. This study was performed to test the hypothesis that CUC-associated PDLs have a different molecular profile than do CUC-associated SAs and therefore may be distinguished on this basis. Mucosal biopsy specimens of 38 benign polypoid epithelial neoplasms (17 CUC-associated PDLs and 21 CUC-associated SAs) from 33 patients with CUC and 13 SAs from patients without CUC (controls) were immunohistochemically stained for p53 and beta catenin and graded as follows: 0 = no staining, 1+ = <50% of cells positive, and 2+ = > or =50% of cells positive. The results were correlated with the clinical and histologic features and compared between the two CUC-associated polyp subgroups. Overall, six (16%) polyps were p53-positive, of which five were CUC-associated PDLs (one 1+ and four 2+) and one was a CUC-associated SA (1+) (p = 0.05). Strong (2+) p53 positivity was detected, however, in only CUC-associated PDLs (4 of 5; 80%). Nine of 32 polyps evaluated for beta catenin were positive and included 1 (8%) of 12 CUC-associated PDLs and 8 (40%) of 20 CUC-associated SAs (p = 0.06). Two of the nine beta catenin polyps were strongly positive, and both were CUC-associated SAs. Non-CUC-associated (control) SAs were positive for p53 and beta catenin in 2 (15%) of 13 and 6 (46%) of 13 cases, but none in a strong (2+) fashion. No differences were observed in p53 or beta catenin staining, between CUC-associated and non-CUC-associated SAs. Neither p53 nor beta catenin expression correlated with any clinical or pathologic features, including size and degree of dysplasia of the polyps. CUC-associated PDLs and CUC-associated SAs may have a different molecular genotype. In patients with CUC, the combination of strong p53 expression and absent or weak beta catenin expression is evidence in favor of a CUC-associated PDL in diagnostically difficult lesions. Furthermore, CUC-associated and non-CUC-associated SAs have a similar P53 and beta catenin immunophenotype and thus provide evidence that they are pathogenetically related neoplasms regardless of the presence or absence of colitis.
在慢性溃疡性结肠炎（CUC）患者中，息肉样发育异常病变（PDL）在形态上与散发性腺瘤（SA）相似，但在生物学特性上可能与之不同，且处理方式也有所不同。与散发性结肠癌发生过程相比，p53突变在CUC相关肿瘤形成的早期阶段就已出现。相反，APC基因突变在SA的发生发展早期很常见。β-连环蛋白是一种细胞膜蛋白，在结肠癌细胞核中因APC基因突变而积累。本研究旨在验证以下假设：CUC相关的PDL与CUC相关的SA具有不同的分子特征，因此可据此进行区分。对33例CUC患者的38个良性息肉样上皮肿瘤（17个CUC相关的PDL和21个CUC相关的SA）以及13个非CUC患者（对照）的SA的黏膜活检标本进行p53和β-连环蛋白免疫组织化学染色，并分级如下：0级 = 无染色，1+级 = ＜50%的细胞阳性，2+级 = ≥50%的细胞阳性。将结果与临床和组织学特征进行关联，并在两个CUC相关息肉亚组之间进行比较。总体而言，6个（16%）息肉p53呈阳性，其中5个是CUC相关的PDL（1个1+级和4个2+级），1个是CUC相关的SA（1+级）（p = 0.05）。然而，仅在CUC相关的PDL中检测到强（2+级）p53阳性（5个中的4个；80%）。在评估β-连环蛋白的32个息肉中，9个呈阳性，包括12个CUC相关PDL中的1个（8%）和20个CUC相关SA中的8个（40%）（p = 0.06）。9个β-连环蛋白阳性息肉中有2个为强阳性，且均为CUC相关的SA。13个非CUC相关（对照）SA中，13个中有2个（15%）p53阳性，13个中有6个（46%）β-连环蛋白阳性，但均无强（2+级）表现。在CUC相关和非CUC相关的SA之间，未观察到p53或β-连环蛋白染色的差异。p53和β-连环蛋白的表达均与任何临床或病理特征无关，包括息肉的大小和发育异常程度。CUC相关的PDL和CUC相关的SA可能具有不同的分子基因型。在CUC患者中，p53强表达且β-连环蛋白表达缺失或减弱的组合，有助于在诊断困难的病变中支持CUC相关的PDL。此外，CUC相关和非CUC相关的SA具有相似的P53和β-连环蛋白免疫表型，因此证明无论是否存在结肠炎，它们都是发病机制相关的肿瘤。
