INTRODUCTION Patients with serrated polyposis syndrome (SPS) have an increased risk to develop colorectal cancer (CRC). Due to an abundance of serrated polyps, these CRCs are assumed to arise mainly through the serrated neoplasia pathway rather than through the classical adenoma-carcinoma pathway. We aimed to evaluate the pathogenetic routes of CRCs in patients with SPS. METHODS We collected endoscopy and pathology data on CRCs and polyps of patients with SPS under treatment in our center. Our primary end point was the proportion of BRAFV600E mutated CRCs, indicating serrated pathway CRCs (sCRCs). CRCs lacking BRAFV600E most likely inferred a classical adenoma-carcinoma origin (aCRCs). We assessed patient, polyp, and CRC characteristics and stratified for BRAFV600E mutation status. RESULTS Thirty-five patients with SPS harbored a total of 43 CRCs. Twenty-one CRCs (48.8%) carried a BRAFV600E mutation, 10 of which lacked MLH1 staining and 17 (81%) were located in the proximal colon. Twenty-two CRCs (51.1%) did not carry a BRAFV600E mutation and were MLH1 proficient. Of these 22 putatively aCRCs, 17 (77.3%) were located distally and one-third (36.4%) harbored a pathogenic KRAS or NRAS mutation. In patients with BRAFwt -CRCs, a higher ratio of the median number of conventional adenomas versus serrated polyps was found (4 vs 13) than patients with BRAFV600E -CRCs (1 vs 14). DISCUSSION Our study indicates that in patients with SPS, the ratio of sCRCs:aCRCs on average is 50:50. This elevated sCRC:aCRC ratio in patients with SPS, when compared with non-SPS patients, correlates well with the differences in the ratios of the numbers of sessile serrated lesions and conventional adenomas in patients with SPS and non-SPS patients, respectively.

中文翻译：

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锯齿状息肉病综合征中的息肉和结直肠癌：经典腺瘤-癌和锯齿状肿瘤途径的贡献。

简介 锯齿状息肉病综合征 (SPS) 患者患结直肠癌 (CRC) 的风险增加。由于大量锯齿状息肉，这些 CRC 被认为主要通过锯齿状肿瘤途径而不是通过经典的腺瘤-癌途径产生。我们的目的是评估 SPS 患者中 CRC 的发病途径。方法收集本中心治疗的SPS患者的CRC和息肉的内镜检查和病理学数据。我们的主要终点是 BRAFV600E 突变 CRC 的比例，表明锯齿状通路 CRC (sCRC)。缺乏 BRAFV600E 的 CRC 最有可能推断出经典的腺瘤癌起源 (aCRC)。我们评估了患者、息肉和 CRC 特征，并对 BRAFV600E 突变状态进行了分层。结果 35 名 SPS 患者总共有 43 个 CRC。21 个 CRC (48.8%) 携带 BRAFV600E 突变，其中 10 个缺乏 MLH1 染色，17 个 (81%) 位于近端结肠。22 名 CRC (51.1%) 不携带 BRAFV600E 突变且精通 MLH1。在这 22 个假定的 aCRC 中，17 个 (77.3%) 位于远端，三分之一 (36.4%) 存在致病性 KRAS 或 NRAS 突变。在 BRAFwt -CRC 患者中，常规腺瘤与锯齿状息肉的中位数比率（4 vs 13）高于 BRAFV600E -CRC 患者（1 vs 14）。讨论 我们的研究表明，在 SPS 患者中，sCRC 与 aCRC 的平均比例为 50:50。与非 SPS 患者相比，SPS 患者的 sCRC:aCRC 比率升高，分别与 SPS 患者和非 SPS 患者的无蒂锯齿状病变和常规腺瘤数量比率的差异密切相关。