Typical and Atypical Carcinoid Tumors of the Mediastinum: A Biomarker Analysis of 27 Cases With Clinical Correlation

Abstract

Thymic typical and atypical carcinoids are rare and appear to be more aggressive than similar tumors in other sites. We retrospectively analyzed a group of biomarkers that hold therapeutic and prognostic utility, in 27 of these tumors. All cases were immunohistochemically stained with PAX5, MET, CRMP5, paxillin, p21, p27, EZH2, PDL-1, and Ki-67, and then H-scored. Clinicopathologic and survival data were statistically analyzed against staining (χ2 test). Five- and 10-year-survival rates were 53% and 18%, respectively. Mitotic counts ≥4 per 2 mm2 and tumor size ≥5 cm, associated with death of disease (DoD; P = .010 and .016). Ki-67 expression ≥1% associated with DoD ( P = .003) and death within 5 years ( P = .031). Biomarkers stained tumor cases as follows: PDL-1 = 0%, PAX-5 = 0%, MET = 7.4%, paxillin = 41%, CRMP5 = 78%, p21 = 63%, p27 = 63%, EZH2 = 37%, and MASH1 = 59%. Overall ± staining did not associate with survival or grade. Cases with low CRMP5 H-scores (<80) associated with DoD ( P = .002), while CRMP5 H-scores >80 associated with 10-year survival ( P = .022). Cases with high MASH1 H-score (>100) associated with DoD ( P = .021). Accurate grading and staging remain paramount in predicting clinical outcome. Biomarkers may have significance in subsets of patients and the use of these studies likely should be focused on a more personalize type of approach.