Department of Pathology, St. Marianna University School of Medicine, Kawasaki, Japan.
Virchows Arch. 2013 Feb;462(2):131-9. doi: 10.1007/s00428-012-1365-1. Epub 2013 Jan 6.
Sessile serrated adenoma/polyps (SSA/Ps) of the colon are thought to be precursors of sporadic carcinomas. Although it is suggested that SSA/P may grow rapidly from the early stage, its cell kinetics remains obscure. To solve this problem, we analyzed the mitotic and apoptotic activity of normal crypts, microvesicular hyperplastic polyps (MVHPs), and tubular adenomas (TAs), using phospho-histone H3 and cleaved caspase 3 immunohistochemistry. The mitotic index for SSA/Ps (mean, 5.63) and TAs (6.98) was significantly higher than those for normal crypts (2.72) and MVHPs (2.86). Of all tested lesions, the apoptotic index was lowest for SSA/Ps (0.96; normal, 2.71; MVHPs, 2.62; TAs, 6.01) with statistically significant differences. The net growth ratio was close to 1.0 in normal crypts (1.07) while remaining low in MVHPs (1.06) and TAs (1.38), but was markedly elevated in SSA/Ps (7.32, P < 0.01) due to the large imbalance between mitosis and apoptosis. As to apoptosis regulatory proteins, expression of anti-apoptotic Bcl-2 was significantly reduced or undetectable in MVHPs and SSA/Ps, while TAs showed stronger staining than normal crypts. Expression of pro-apoptotic Bax and its activators, Bim and Bad, was significantly reduced in MVHPs and SSA/Ps. We suggest that other complex mechanisms may act synergistically with Bax, Bim, or Bad deficiency to regulate apoptosis suppression in SSA/Ps.
结肠无蒂锯齿状腺瘤/息肉（SSA/Ps）被认为是散发性癌的前体。尽管有人认为 SSA/P 可能会从早期快速生长，但它的细胞动力学仍然不清楚。为了解决这个问题，我们使用磷酸化组蛋白 H3 和 cleaved caspase 3 免疫组化分析了正常隐窝、微小泡状增生性息肉（MVHPs）和管状腺瘤（TAs）的有丝分裂和凋亡活性。SSA/Ps（平均值为 5.63）和 TAs（6.98）的有丝分裂指数明显高于正常隐窝（2.72）和 MVHPs（2.86）。在所有测试的病变中，SSA/Ps 的凋亡指数最低（0.96；正常为 2.71；MVHPs 为 2.62；TAs 为 6.01），差异具有统计学意义。净生长比在正常隐窝中接近 1.0（1.07），而在 MVHPs（1.06）和 TAs（1.38）中仍然较低，但在 SSA/Ps 中明显升高（7.32，P<0.01），这是由于有丝分裂和凋亡之间的严重失衡。至于凋亡调节蛋白，抗凋亡 Bcl-2 的表达在 MVHPs 和 SSA/Ps 中显著降低或无法检测到，而 TAs 的染色强度强于正常隐窝。促凋亡 Bax 及其激活剂 Bim 和 Bad 的表达在 MVHPs 和 SSA/Ps 中显著降低。我们认为，其他复杂的机制可能与 Bax、Bim 或 Bad 缺陷协同作用，调节 SSA/Ps 中的凋亡抑制。
