Mucin core protein expression in colorectal cancers with high levels of microsatellite instability indicates a novel pathway of morphogenesis.
Mucin core protein expression in colorectal cancers with high levels of microsatellite instability indicates a novel pathway of morphogenesis.
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发表时间：
2000-05
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通讯作者：
A. Biemer-Hüttmann;M. Walsh;M. McGuckin;L. Simms;Joanne P. Young;B. Leggett;J. Jass
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作者：
A. Biemer-Hüttmann;M. Walsh;M. McGuckin;L. Simms;Joanne P. Young;B. Leggett;J. Jass
特定的粘液性表型与结肠的锯齿状上皮息肉有关。这些息肉也显示出高频率的DNA不稳定性。本研究的目的是检查结直肠癌中通过抑制和突变途径产生的粘蛋白的表达。人脱粘蛋白MUC 1、MUC 2、MUC 4和MUC 5AC的免疫组织化学分布在先前分类的93个散发性结肠直肠癌中测定（J. R. Jass等人，临床病理学杂志，52：455-460，1999），根据DNA微卫星不稳定性（MSI）的水平，将其分为22个MSI-高（MSI-H）、24个MSI-低（MSI-L）和47个MS稳定（MSS）。在19例（86%）MSI-H、10例（42%）MSI-L和15例（32%）MSS癌症中观察到MUC 2表达（P = 0.0001）;在17例（77%）MSI-H、8例（33%）MSI-L和13例（28%）MSS癌症中观察到MUC 5AC表达（P = 0.0003）。MUC 1和MUC 4的表达与MSI状态无关。锯齿状息肉中描述的粘液性表型（MUC 2 +/MUC 5AC+）见于22例MSI-H中的15例（68%）和71例MSI-L/MSS癌中的仅10例（14%）（P < 0.0001）。在散发性MSI-H癌中观察到分泌性粘蛋白MUC 2和MUC 5AC的表达增加。结直肠锯齿状息肉中出现相同的粘蛋白改变和DNA MSI，这表明这些病变可能代表MSI-H癌的前兆。
Particular mucinous phenotypes have been associated with serrated epithelial polyps of the colon. These polyps also show a high frequency of DNA instability. The aim of this study was to examine the expression of mucins in colorectal cancers that arise through the suppressor and mutator pathways. The immunohistochemical distribution of the human apomucins MUC1, MUC2, MUC4, and MUC5AC was determined in 93 sporadic colorectal cancers classified previously (J. R. Jass et al., J. Clin. Pathol., 52: 455-460, 1999) according to levels of DNA microsatellite instability (MSI) as 22 MSI-high (MSI-H), 24 MSI-low (MSI-L), and 47 MS stable (MSS). MUC2 expression was observed in 19 (86%) MSI-H, 10 (42%) MSI-L, and 15 (32%) MSS cancers (P = 0.0001); and MUC5AC expression was observed in 17 (77%) MSI-H, 8 (33%) MSI-L, and 13 (28%) MSS cancers (P = 0.0003). There was no association between MUC1 or MUC4 expression and MSI status. The mucinous phenotype described in serrated polyps (MUC2+/MUC5AC+) was seen in 15 (68%) of 22 MSI-H and only 10 (14%) of 71 MSI-L/MSS cancers (P < 0.0001). Increased expression of the secretory mucins MUC2 and MUC5AC was observed in sporadic MSI-H cancers. Identical mucin changes and DNA MSI occurred in serrated polyps of the colorectum, which suggests that these lesions may represent precursors of MSI-H cancers.