Division of Anatomical Pathology, Department of Medicine, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, N.S., Canada.
Neuroendocrinology. 2011;93(4):249-58. doi: 10.1159/000326820. Epub 2011 Apr 10.
There has been limited study of estrogen and progesterone receptor (ER/PR) expression in gastrointestinal neuroendocrine tumors (GINETs) despite emerging evidence of hormone receptor regulation of pancreatic islet cells. Beta cells express PR and progesterone has been implicated in the pathogenesis of gestational diabetes. There is conflicting information regarding HER2/neu protein overexpression in GINETs. Investigation of ER, PR and HER2/neu expression in GINETs is therefore warranted.
A pathology database search identified 77 patients with primary pancreatic (40) or small intestinal (37) NETs diagnosed from 1991 to 2009. Ki67, ER, PR and HER2/neu were assessed via immunohistochemistry. ER and PR were interpreted as negative (0), 1+ (Allred score 3-7/8) or 2+ (Allred score 8/8), and HER2/neu was assessed according to ASCO/CAP guidelines for breast carcinoma. Clinical correlation and survival outcomes were ascertained by a retrospective clinical chart review.
2+ PR staining was observed more often in pancreatic compared to small intestinal cases (55 vs. 8%; p < 0.001). All small intestinal NETs with 2+ PR were duodenal primaries. Cases with 2+ PR presented significantly less often with nodal or distant metastases compared to cases with 0/1+ PR (13 vs. 61.5%; p < 0.001) and had significantly improved disease-free survival (median 155 vs. 38 months; p = 0.037). Only one case demonstrated 2+ ER staining and all were negative for HER2/neu.
GINETs with strong (2+) PR expression are associated with pancreatic/duodenal origin, lower stage disease, and more favorable clinical prognosis. Further study is needed to determine the clinical utility of PR expression in GINETs.
尽管有越来越多的证据表明激素受体调节胰岛细胞，但胃肠道神经内分泌肿瘤（GINETs）中雌激素和孕激素受体（ER/PR）的表达研究有限。β细胞表达 PR，孕激素已被牵连到妊娠糖尿病的发病机制中。关于 GINETs 中 HER2/neu 蛋白过表达存在矛盾的信息。因此，有必要对 GINETs 中 ER、PR 和 HER2/neu 的表达进行研究。
通过病理数据库搜索，确定了 1991 年至 2009 年间诊断的 77 例原发性胰腺（40 例）或小肠（37 例）NETs 患者。通过免疫组织化学评估 Ki67、ER、PR 和 HER2/neu。ER 和 PR 的解释为阴性（0）、1+（Allred 评分 3-7/8）或 2+（Allred 评分 8/8），HER2/neu 根据乳腺癌 ASCO/CAP 指南进行评估。通过回顾性临床图表审查确定临床相关性和生存结果。
与小肠病例相比，胰腺病例中观察到更多的 2+PR 染色（55%比 8%；p <0.001）。所有 2+PR 的小肠 NET 均为十二指肠原发性肿瘤。与 0/1+PR 相比，2+PR 病例淋巴结或远处转移的发生率显著降低（13%比 61.5%；p <0.001），无病生存时间显著延长（中位数 155 比 38 个月；p = 0.037）。仅 1 例显示 2+ER 染色，所有病例均为 HER2/neu 阴性。
具有强（2+）PR 表达的 GINETs 与胰腺/十二指肠起源、较低的疾病分期和更好的临床预后相关。需要进一步研究以确定 PR 表达在 GINETs 中的临床应用价值。
