Table 2.
Overview of immunohistochemical features of studies that performed OTP analyses.
| Study Year [Ref] | Immunohistochemistry | Outcome (n OTP Positive/Total (%)) | Staining Scoring | |||||
|---|---|---|---|---|---|---|---|---|
| Antibody Supplier # | Dilution | DIPNECH | TC | AC | HGNECs | Considered Positive If | Overall Conclusion | |
| Hanley et al., 2018 [18] | Sigma | (1:800) | - | 9/9 (100%) | 1/6 (17%) | - | Any percentage or intensity of nuclear OTP expression | OTP is a highly sensitive and specific marker for lung carcinoids |
| Nonaka et al., 2016 * [17] | Atlas | (1:150) | 7/7 (100%) | 105/123 (85.4%) | 10/21 (47.6%) | 2/104 (1.9%) | 1 + (1–25%), 2 + (25–50%), 3 + (50–75%), 4 + (>75%) |
OTP may serve as a useful diagnostic marker for lung carcinoid tumors |
| Papaxoinis et al., 2018 * [19] | Atlas | (1:150) | 16/16 (100%) | 117/132 (88.6%) | 21/34 (61.8%) | - | More than 5% of the tumor expressed a positive reaction | OTP and TTF1 expression can be used to classify carcinoids into different clusters |
| Papaxoinis et al., 2017 * [15] | Atlas | (1:150) | - | nOTP < 150 14/69 (20.3%) |
nOTP <150 8/17 (47%) |
- | H-score (ranging from 0–300) | CD44/nOTP expression is an independent predictor of RFS in patients with radically operated PCs |
| cOTP < 150 59/69 (86%) |
cOTP < 150 14/17 (82%) | - | ||||||
| nOTP > 150 55/69 (80%) |
nOTP > 150 9/17 (53%) |
- | ||||||
| cOTP > 150 10/69 (14.5%) |
cOTP > 150 3/17 (18%) |
- | ||||||
| Swarts et al., 2013 [14] |
Atlas | (1:800) | - | nOTP 10/225 (4%) |
nOTP 3/63 (5%) |
nOTP 1/59 (2%) |
0 = no staining, 1 = very weak diffuse staining [cytoplasm] or staining in single or very few nuclei, 2 = weak to moderate staining, for nuclear staining in >40% of nuclei, 3–4 = strong to very strong staining in most or all tumor cells, respectively. |
OTP and CD44 are powerful prognostic markers for pulmonary carcinoids |
| nOTP + cOTP 165/225 (73%) | nOTP + cOTP 28/63 (44%) | nOTP + cOTP 4/59 (7%) | ||||||
| cOTP 17/225 (8%) |
cOTP 15/63 (24%) |
cOTP 8/59 (14%) |
||||||
| Yoxtheimer et al., 2018 [20] | Sigma | (1:800) | - | 4/8 (50%) | 1/6 (17%) | 1/16 (6.3%) | Min. 5% of tumor cell positivity of 3 + staining intensity | OTP may be used to grade pulmonary NETs and differentiate them from low-grade NETs originating in other sites |
| Viswanathan et al., 2019 [21] | Sigma | (1:800) | - | 9/11 (82%) | 8/12 (80%) | 0/19 (0%) | Tumor showed >1 + OTP staining in >5% of the tumor within the specimen | OTP is a promising highly sensitive and specific marker for primary pulmonary carcinoid tumors |
* studies performed in the same study population. # All studies used the rabbit anti-OTP polyclonal antibody clone HPA039365. Abbreviations: Ref, reference; n, number; OTP, orthopedia homeobox; DIPNECH, diffuse idiopathic neuroendocrine cell hyperplasia; TC, typical carcinoid; AC, atypical carcinoid; HGNECs, high-grade neuroendocrine carcinomas e.g., large cell neuroendocrine carcinoma and small cell lung carcinoma; TTF1, thyroid transcription factor 1; CD44, cell-surface glycoprotein; nOTP, nuclear OTP expression; cOTP, cytoplasmic OTP expression; RFS, Relapse free survival; PCs, pulmonary carcinoids; NETs, neuroendocrine tumors.