Histopathology Department, Middlemore Hospital, Auckland, New Zealand.
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Histopathology. 2019 Sep;75(3):376-384. doi: 10.1111/his.13874. Epub 2019 Jul 2.
Dysplasia in colonic sessile serrated adenomas (SSAs)/sessile serrated polyps often shows loss of MLH1 expression as determined with immunohistochemistry, but the significance of loss of MLH1 expression in non-dysplastic crypts in these polyps is less well studied. The purpose of this study was to evaluate the prevalence of loss of MLH1 expression in non-dysplastic crypts in SSAs, and to evaluate its significance with regard to progression of these polyps.
Four hundred SSAs, including 158 SSAs without dysplasia, 219 SSAs with dysplasia (SSAD), and 23 SSAs with invasive adenocarcinoma (SSAC), were evaluated immunohistochemically for loss of MLH1 expression in both non-dysplastic and dysplastic portions of the polyps. Seventy-one of 400 (18%) SSAs showed loss of MLH1 expression in non-dysplastic crypts. The prevalence of MLH1-deficient non-dysplastic crypts was higher in polyps with dysplasia or carcinoma (7%, 22%, and 52% in SSAs, SSADs, and SSACs, respectively; P < 0.0001). When SSAs with MLH1-deficient dysplasia and those with MLH-1-proficient dysplasia were compared, those with MLH1-deficient dysplasia were more likely to have MLH1-deficient non-dysplastic crypts (66% versus 8.1%, P < 0.0001) and a greater number of discrete foci (3.6 foci versus 1.1 foci, P = 0.008). Also, non-dysplastic crypts with loss of MLH1 expression were more likely to be contiguous with the dysplasia when the dysplasia also showed loss of MLH1 expression (26% versus 0%, P = 0.02).
Our results suggest that loss of MLH1 expression in non-dysplastic crypts in SSAs precedes the development of MLH1-deficient dysplasia and adenocarcinoma, and may be a biomarker of an advanced serrated polyp even in the absence of dysplasia.
在经免疫组织化学检测中，结直肠无蒂锯齿状腺瘤（SSA）/无蒂锯齿状息肉中常出现 MLH1 表达缺失，但这些息肉中无锯齿状增生的非增生性隐窝中 MLH1 表达缺失的意义研究较少。本研究旨在评估 SSAs 中无锯齿状增生的非增生性隐窝中 MLH1 表达缺失的发生率，并评估其与这些息肉进展的关系。
对 400 个 SSA 进行了评估，包括 158 个无锯齿状增生的 SSA、219 个有锯齿状增生的 SSA（SSAD）和 23 个有侵袭性腺癌的 SSA（SSAC），用免疫组化方法检测这些息肉的非增生性和增生性部分中 MLH1 表达缺失。400 个 SSA 中有 71 个（18%）在非增生性隐窝中出现 MLH1 表达缺失。在有增生或癌的息肉中，MLH1 缺失的非增生性隐窝的发生率更高（SSA、SSAD 和 SSAC 中的发生率分别为 7%、22%和 52%；P<0.0001）。当比较 MLH1 缺失的锯齿状增生和 MLH1 阳性的锯齿状增生的 SSA 时，MLH1 缺失的锯齿状增生的 SSA 更有可能出现 MLH1 缺失的非增生性隐窝（66%比 8.1%，P<0.0001）和更多的离散病灶（3.6 个病灶比 1.1 个病灶，P=0.008）。此外，当增生也缺失 MLH1 表达时，缺失 MLH1 表达的非增生性隐窝更有可能与增生连续（26%比 0%，P=0.02）。
我们的结果表明，SSA 中无锯齿状增生的非增生性隐窝中 MLH1 表达缺失先于 MLH1 缺失的锯齿状增生和腺癌的发生，并且即使没有锯齿状增生，它也可能是高级锯齿状息肉的生物标志物。
