Send to

Choose Destination
Cancer Cytopathol. 2018 Apr;126(4):236-242. doi: 10.1002/cncy.21969. Epub 2018 Jan 9.

Orthopedia homeobox is preferentially expressed in typical carcinoids of the lung.

Author information

Department of Pathology, Emory University, Atlanta, Georgia.
Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia.



Twenty-seven percent of neuroendocrine tumors (NETs) are associated with distant metastases, and in some patients, the primary site is unknown. Orthopedia homeobox protein (OTP) has been described as a useful marker for lung carcinoids (LCs) and for separating low-grade typical carcinoids (TCs) from intermediate-grade atypical carcinoids (ACs) in resection specimens. This study evaluated OTP, thyroid transcription factor 1 (TTF-1), and Ki-67 expression in fine-needle aspiration (FNA) samples of various NETs.


A search for NETs diagnosed via FNA with subsequent resection was performed. Cell block sections were stained for OTP, TTF-1, and mindbomb E3 ubiquitin protein ligase 1 (Mib-1). Nuclear expression for OTP and TTF-1 was considered positive. Nuclear Ki-67 staining was reported as a percentage. Results were correlated with the grade and primary site for resection specimens.


Sixty-three FNA samples of NETs were identified: 14 liver samples, 14 pancreatic samples, 13 lymph node samples, 12 lung samples, 3 retroperitoneum samples, 2 small intestine samples, and 5 other samples. OTP was positive in 12 of 63 NETs (19%) from the following sites: lung (n = 8), liver (lung primary; n = 2), skin (n = 1), and lymph node (lung primary; n = 1). In well-differentiated NETs, only LCs were OTP-positive, whereas TTF-1 was positive in LCs and nonlung NETs (67% vs 7%). Within the LC category, OTP was positive in 100% of the TCs versus 17% of the ACs.


OTP is specific for LCs because well-differentiated nonlung NETs are negative for OTP. OTP preferentially stains TCs over ACs. In well-differentiated NETs, OTP staining is highly specific for LCs, and in combination with a low Ki-67 index, it suggests a pulmonary TC. Cancer Cytopathol 2018;126:236-42. © 2018 American Cancer Society.


Ki-67; atypical carcinoid; carcinoid; neuroendocrine neoplasm; orthopedia homeobox protein (OTP); thyroid transcription factor 1 (TTF-1)

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center