Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.
Clin Transl Gastroenterol. 2023 Aug 1;14(8):e00611. doi: 10.14309/ctg.0000000000000611.
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.
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.
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).
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.
锯齿状息肉综合征（SPS）患者结直肠癌（CRC）的风险增加。由于锯齿状息肉较多，这些 CRC 被认为主要通过锯齿状肿瘤发生途径而不是经典的腺瘤-癌途径发生。我们旨在评估 SPS 患者 CRC 的发病途径。
我们收集了在我们中心接受治疗的 SPS 患者的 CRC 和息肉的内镜和病理数据。我们的主要终点是 BRAFV600E 突变的 CRC 比例，表明锯齿途径 CRC（sCRC）。缺乏 BRAFV600E 的 CRC 最有可能提示经典的腺瘤-癌起源（aCRC）。我们评估了患者、息肉和 CRC 的特征，并按 BRAFV600E 突变状态进行分层。
35 例 SPS 患者共发现 43 例 CRC。21 例 CRC（48.8%）携带 BRAFV600E 突变，其中 10 例缺乏 MLH1 染色，17 例（81%）位于近端结肠。22 例 CRC（51.1%）未携带 BRAFV600E 突变且 MLH1 正常。在这 22 例假定的 aCRCs 中，17 例（77.3%）位于远端，三分之一（36.4%）携带致病性 KRAS 或 NRAS 突变。在 BRAFwt-CRCs 患者中，常规腺瘤与锯齿状息肉中位数的比值（4 比 13）高于 BRAFV600E-CRCs 患者（1 比 14）。
我们的研究表明，在 SPS 患者中，sCRC：aCRC 的平均比例为 50：50。与非 SPS 患者相比，SPS 患者中 sCRC：aCRC 比值升高，与 SPS 和非 SPS 患者中分别存在的无蒂锯齿状病变和常规腺瘤数量比值的差异相吻合。
