Departments of *Surgery ¶¶Laboratory Medicine ##Laboratory for Mathematics, National Defense Medical College, Tokorozawa †Department of Surgery, Kurume University Faculty of Medicine, Kurume Departments of ‡Human Pathology ***Surgery, Tokyo Medical and Dental University ¶Department of Pathology, National Cancer Center Hospital #Department of Pathology, Jikei University School of Medicine, Tokyo §Department of Surgery, Coloproctology Center, Takano Hospital, Kumamoto ∥Department of Surgery, Keiyukai Sappro Hospital, Sapporo **Department of Surgery, Hirosaki University School of Medicine, Hirosaki ††Department of Surgery, Kinki University School of Medicine, Osakasayama ‡‡Department of Surgery, Yamagata Prefectural Central Hospital, Yamagata §§Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Course for Molecular and Cellular Medicine, Niigata University, Niigata ∥∥Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Am J Surg Pathol. 2013 Oct;37(10):1542-9. doi: 10.1097/PAS.0b013e318297ef6e.
Perineural invasion (PN) in colorectal cancer (CRC) is a site-specific prognostic marker, as mentioned by the AJCC Cancer Staging Manual, but it remains to be clearly defined. We aimed to identify an optimal characterization of PN as a component of cancer staging. On the basis of the anatomic features of the nervous system of the large bowel, site-specific pathologic criteria were assigned to PN according to the location of PN. Multi-institutional pathologic review based on these criteria was performed for 962 patients with stage I to III CRC at 2 institutions (1999 to 2004, cohort 1) and 1883 patients from 8 other institutions (2000 to 2004, cohort 2). In cohort 1, intramural and extramural PN were observed in 152 and 101 patients, respectively, which had a different impact on disease-free survival (hazard ratio, 2.6 [1.9 to 3.5] vs. 4.7 [3.4 to 6.5], respectively). A 3-tiered grading system (Pn0; Pn1a, intramural PN; Pn1b, extramural PN) distinguished 5-year disease-free survival as 88%, 70%, and 48%, respectively; and multivariate analysis identified PN grade as a significant prognostic marker independent of T or N stage. These results were similar in cohort 2. Interinstitutional difference of the prognostic impact of PN grade was acceptably small among all institutions. Interobserver study among 6 gastrointestinal pathologists showed superior judgment reproducibility for PN compared with vascular invasion. The results of our study indicate that PN is an important prognostic marker in CRC. The value of cancer staging could be enhanced by PN assessment using site-specific criteria and a simple grading system based on PN location within the bowel.
神经周围侵犯（PN）在结直肠癌（CRC）中是一种特定于部位的预后标志物，正如 AJCC 癌症分期手册所述，但仍需明确界定。我们旨在确定 PN 作为癌症分期组成部分的最佳特征。基于大肠神经系统的解剖学特征，根据 PN 的位置对 PN 进行了特定于部位的病理标准分配。在 2 个机构（1999 年至 2004 年，队列 1）的 962 例 I 期至 III 期 CRC 患者和其他 8 个机构（2000 年至 2004 年，队列 2）的 1883 例患者中，基于这些标准进行了多机构病理复查。在队列 1 中，分别有 152 例和 101 例患者观察到壁内和壁外 PN，它们对无病生存有不同的影响（风险比，2.6 [1.9 至 3.5] 与 4.7 [3.4 至 6.5]）。三级分级系统（Pn0；Pn1a，壁内 PN；Pn1b，壁外 PN）区分了 5 年无病生存率，分别为 88%、70%和 48%；多变量分析确定 PN 分级是独立于 T 或 N 分期的重要预后标志物。队列 2 中的结果相似。在所有机构中，PN 分级的预后影响的机构间差异可接受地较小。6 位胃肠病理学家的观察者间研究表明，PN 的判断重现性优于血管侵犯。我们的研究结果表明，PN 是 CRC 的一个重要预后标志物。通过使用特定于部位的标准和基于 PN 在肠内位置的简单分级系统评估 PN，可以提高癌症分期的价值。
