Ozturk Sari Sule, Taskin Orhun Cig, Gundogdu Gokcen, Yegen Gulcin, Onder Semen, Keskin Metin, Saglam Sezer, Ozluk Yasemin, Gulluoglu Mine, Mete Ozgur
Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Endocr Pathol. 2016 Jun;27(2):162-70. doi: 10.1007/s12022-016-9424-9.
This study investigated the impact of phosphohistone-H3 (PHH3)-assisted mitotic count by comparing its performance with conventional mitotic count and Ki67 score as well as the status of distant metastasis. A total of 43 surgically resected pancreatic neuroendocrine tumors (panNET) with complete follow-up information has been subjected to a standardized assessment with respect to mitotic count (both conventional and PHH3-assisted) and Ki67 score. Five participants assessed mitotic count and the time spent was recorded in both methods. All tumors were assigned to a G1 category of mitotic rate on conventional mitotic count that failed to identify three tumors with a G2 category of mitotic rate on PHH3. Near-perfect and fair agreements were achieved among observers when using PHH3 and conventional method, respectively. The mean time spent to determine mitotic count on PHH3-stained slides was significantly shorter (p < 0.001). The performance of PHH3-assisted mitotic grade category was significant as the three cases with a G2 mitotic category were associated with distant metastasis (p = 0.01). Despite its performance, the PHH3-assisted mitotic count downgraded 17 cases that were classified as G2 based on Ki67 scores in this series. The Ki67 grade category was either the same or higher than the mitotic grade category. Ten patients developed distant metastasis. Eleven tumors exhibited vascular invasion characterized by intravascular tumor cells admixed with thrombus. Our results indicate that PHH3-assisted mitotic count facilitates an accurate mitotic count with a perfect agreement among observers. The small size of this cohort is an important limitation of the current study, a G2 mitotic grade category based on PHH3 immunohistochemistry was one of the correlates of panNETs with distant metastasis. While the prognostic impact of PHH3-assisted mitotic count needs to be clarified in larger cohorts, Ki67 scores designated higher grade category in all cases; thus, it was the best determinant of the tumor grade. More importantly, the presence of vascular invasion along with the Ki67 grade category was found to be independent predictors of distant metastasis.
本研究通过将磷酸化组蛋白-H3（PHH3）辅助的有丝分裂计数与传统有丝分裂计数、Ki67评分以及远处转移状态进行比较，调查了其影响。共有43例接受手术切除且有完整随访信息的胰腺神经内分泌肿瘤（panNET）接受了关于有丝分裂计数（传统和PHH3辅助）和Ki67评分的标准化评估。5名参与者评估有丝分裂计数，并记录两种方法所花费的时间。所有肿瘤在传统有丝分裂计数中被归类为有丝分裂率G1级，但其中3例在PHH3检测中为有丝分裂率G2级。使用PHH3和传统方法时，观察者之间分别达成了近乎完美和一般的一致性。在PHH3染色切片上确定有丝分裂计数所花费的平均时间显著更短（p < 0.001）。PHH3辅助的有丝分裂分级类别的表现具有显著性，因为3例有丝分裂类别为G2级的病例与远处转移相关（p = 0.01）。尽管有其表现，但在本系列中，PHH3辅助的有丝分裂计数将17例基于Ki67评分被归类为G2级的病例降级。Ki67分级类别与有丝分裂分级类别相同或更高。10例患者发生远处转移。11个肿瘤表现出血管侵犯，其特征为血管内肿瘤细胞与血栓混合。我们的结果表明，PHH3辅助的有丝分裂计数有助于准确计数有丝分裂，观察者之间达成了完美的一致性。本队列规模较小是当前研究的一个重要局限，基于PHH3免疫组化的有丝分裂G2级类别是panNETs与远处转移的相关因素之一。虽然PHH3辅助的有丝分裂计数的预后影响需要在更大的队列中阐明，但在所有病例中Ki67评分指定了更高的分级类别；因此，它是肿瘤分级的最佳决定因素。更重要的是，发现血管侵犯的存在以及Ki67分级类别是远处转移的独立预测因素。
