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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

1
Department of Pathology, Emory University, Atlanta, Georgia.
2
Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

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

PMID:
29316326
DOI:
10.1002/cncy.21969
[Indexed for MEDLINE]
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