Lee Hwajeong, Fu Zhiyan, Koo Brandon H, Sheehan Christine E, Young Gloria Q, Lin Jingmei, Patil Deepa T, Yang Zhaohai
Anatomic Pathology, Albany Medical College, Albany, NY, USA.
Albany Medical College, Albany, NY, USA.
Ann Diagn Pathol. 2018 Dec;37:30-34. doi: 10.1016/j.anndiagpath.2018.09.005. Epub 2018 Sep 13.
The expression profile of immunohistochemical markers of origin in poorly differentiated neuroendocrine carcinoma (PDNEC) is not well studied.
Seventy-four PDNECs from gastroenteropancreatic (GEP) organs and the lung, including 48 large cell NEC (LCNEC) and 26 small cell carcinomas (SmCC), were subject to immunohistochemical staining for CDX2, TTF1 and ISL1. The staining intensity (1 to 3) and percentage of positive tumor cells [0 (negative), 1 (<50%) and 2 (≥50%)] were assessed. The multiplicative index (maximum 6) was calculated and the average total score (aTS) was determined for each primary site and histologic subtype.
In the 38 GEP and 36 lung PDNECs, CDX2, TTF1 and ISL1 staining was observed in 71% (aTS 2.8), 16% (aTS 0.4), 63% (aTS 1.9), and 22% (aTS 0.6), 72% (aTS 2.9) and 92% (aTS 3.8), respectively. GEP PDNECs showed a higher aTS for CDX2 and lower aTS for TTF1 and ISL1, compared to that of lung PDNECs (Student's t-test, p < 0.001). SmCC had a higher aTS for TTF1 and ISL1 (p < 0.001) and lower aTS for CDX2 (p < 0.002) than that of LCNEC.
CDX2 and TTF1 demonstrate potential utility in suggesting the primary site of PDNEC. In addition, CDX2 may be useful in supporting the diagnosis of LCNEC in cases with overlapping or borderline morphology. Utility of ISL1 as an adjunctive diagnostic marker of SmCC remains to be studied.
低分化神经内分泌癌（PDNEC）中起源相关免疫组化标志物的表达谱尚未得到充分研究。
对74例来自胃肠胰（GEP）器官和肺的PDNEC进行研究，其中包括48例大细胞神经内分泌癌（LCNEC）和26例小细胞癌（SmCC），对其进行CDX2、TTF1和ISL1的免疫组化染色。评估染色强度（1至3级）和阳性肿瘤细胞百分比[0（阴性）、1（<50%）和2（≥50%）]。计算乘积指数（最大值为6），并确定每个原发部位和组织学亚型的平均总分（aTS）。
在38例GEP和36例肺PDNEC中，CDX2、TTF1和ISL1染色阳性率分别为71%（aTS 2.8）、16%（aTS 0.4）、63%（aTS 1.9），以及22%（aTS 0.6）、72%（aTS 2.9）和92%（aTS 3.8）。与肺PDNEC相比，GEP PDNEC的CDX2的aTS更高，TTF1和ISL1的aTS更低（Student t检验，p<0.001）。与LCNEC相比，SmCC的TTF1和ISL1的aTS更高（p<0.001），CDX2的aTS更低（p<0.002）。
CDX2和TTF1在提示PDNEC的原发部位方面具有潜在作用。此外，在形态学重叠或临界的病例中，CDX2可能有助于支持LCNEC的诊断。ISL1作为SmCC辅助诊断标志物的作用仍有待研究。
