Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan.
Sci Rep. 2019 Feb 20;9(1):2404. doi: 10.1038/s41598-018-37707-z.
Rectal neuroendocrine tumors (NETs) are often found as small lesions, which can be treated by endoscopic resection. However, high risk cases with lymph node (LN) metastasis are indication of radical surgery. Furthermore, rectal NETs are often associated with late recurrences and/or multiple cancer development. Therefore, proper surgical indication and patients' management are required. We investigated the clinicopathological features of 79 rectal NET cases in order to elucidate risk factors for synchronous LN metastasis, recurrence, and multiple cancers. Recently, we reported that in pancreatic NET patients, a loss of heterozygosity (LOH) in PHLDA3 was associated with poorer prognosis, and that LOH of both PHLDA3 and MEN1 was frequently observed. Therefore, PHLDA3 and MEN1 LOH were also assessed in rectal NET patients for their association with clinicopathological features. Of the 79 patients, LN metastases were found in 12.7%, recurrences in 3.8%, and multiple cancers in 30.4% of the subjects. PHLDA3 and MEN1 LOH were found in 60.0% and 66.7% of the subjects, respectively. Lymphatic invasion and WHO classification 2010 were found to be independent risks for LN metastasis. There were three cases of recurrence, all of which occurred more than 3 years after resection and two of which exhibited LN metastasis. Older age and LOH in PHLDA3 were associated with the presence of multiple cancers. Long-term and systemic management of patients with rectal NETs is therefore recommended in accordance with these risk factors.
直肠神经内分泌肿瘤（NET）常以小病灶形式存在，可通过内镜切除治疗。然而，存在淋巴结（LN）转移的高危病例则需要根治性手术。此外，直肠 NET 常伴有晚期复发和/或多发癌症。因此，需要合理的手术适应证和患者管理。我们研究了 79 例直肠 NET 病例的临床病理特征，以阐明同步 LN 转移、复发和多发癌症的危险因素。最近，我们报道在胰腺 NET 患者中，PHLDA3 的杂合性缺失（LOH）与预后不良相关，并且 PHLDA3 和 MEN1 的 LOH 常同时发生。因此，我们还评估了直肠 NET 患者中 PHLDA3 和 MEN1 的 LOH 与其临床病理特征的相关性。在 79 例患者中，12.7%的患者发生 LN 转移，3.8%的患者复发，30.4%的患者发生多发癌症。PHLDA3 和 MEN1 的 LOH 分别见于 60.0%和 66.7%的患者。淋巴管浸润和 2010 年 WHO 分级被认为是 LN 转移的独立危险因素。有 3 例复发，均发生在切除 3 年以后，其中 2 例发生 LN 转移。高龄和 PHLDA3 的 LOH 与多发癌症的发生相关。因此，建议对直肠 NET 患者进行长期和系统性管理，以应对这些危险因素。
