Absence of orthopaedia homeobox protein (OTP) expression is associated with disease spread and adverse outcome in pulmonary carcinoid tumour patients

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Pulmonary carcinoid (PC) tumours typically have a good prognosis, although metastases occur, and the disease may progress after a long period of time. Expression of orthopaedia homeobox protein (OTP) has been recognized as a possible independent prognostic marker in PCs. Immunohistochemical (IHC) OTP expression has been associated with better prognosis, but the staining has yet to be implemented in routine clinical diagnostics. In response to this, two new monoclonal OTP antibodies were recently developed.This retrospective study included 164 PC patients operated on at Helsinki University Hospital between 1990 and 2020. Tissue microarray slides, prepared from formalin-fixed and paraffin-embedded primary tumour samples, were stained with OTP IHC using one polyclonal and two novel monoclonal antibodies.Absence of OTP expression was associated with a shorter disease-specific survival (DSS) and disease progression (p < 0.001). Patients without OTP expression had a 5-year DSS of 73-79%, whereas 5-year DSS was 91-94% with OTP expression, depending on the primary antibody. In a univariable Cox regression model, absence of OTP expression was associated with adverse outcome along with atypical histological subtype, metastatic disease, Ki-67 proliferation index > 1%, and larger tumour size. In a multivariable Cox regression model, only absence of OTP expression and lymph node involvement at the time of diagnosis were associated with risk of worse prognosis. All three antibodies showed good concordance with each other.Our findings support the role of OTP as an independent prognostic marker in PCs and applicability of IHC staining in routine clinical use with novel monoclonal antibodies.

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