A multimodal biomarker predicts dissemination of bronchial carcinoid

Abstract IntroductionThe extensive loss of lung parenchyma is a drawback of anatomical resection in bronchial carcinoids. Endobronchial therapy (EBT) has emerged as a safe and effective minimally invasive tissue sparing alternative for small intraluminal tumors. Currently, therapeutic decision making in patients with bronchial carcinoid is mainly based on tumor morphology and patient characteristics. The availability of more accurate biomarkers might help clinicians in selecting low-risk tumors for EBT. Therefore, we investigated radiological (tumor diameter), morphometric (mitotic index) and immunohistochemical (OTP, CD44, Ki-67, Rb and P16) markers as predictors of dissemination. Material and methodsPatients referred to Amsterdam University Medical Centers with available histology were included. Clinical and morphological characteristics relevant for classification such as tumor diameter, mitotic count (MAI) and prognostic immunohistochemical markers as Ki-67, P16, Rb, Orthopedia homebox (OTP) and CD44 were analyzed. ResultsIn a cohort of 171 patients, the vast majority were curatively treated with either EBT (n=61, 36%) or surgery (n=103, 60%). Seven (4%) patients presented with distant metastases at diagnosis. TC was diagnosed in 112 (65%) and AC in 59 (35%) patients. Nine (15%) patients treated with EBT had a local recurrence of disease during follow up and none developed lymph node or distant metastasis. Of all surgically treated patients, 13 (13%) had level 1 or 2 lymph node metastases. Additional 13 (13%) patients developed distant metastases, 11 (85%) were AC and 2 (15%) TC. Patients with tumor stage IA (tumor diameter ≤1cm) irrespective of tumor classification or immunohistochemical results did not develop distant metastases. Patients with typical carcinoid (<2 mitoses per 2 mm2) stage ≥IB with Ki67 <5% and positive CD44 did not develop distant metastases either. All patients with atypical carcinoid (≥2 mitoses 2 mm2), Ki-67 of ≥5% (p=<0.000) and loss of CD44 (p=<0.0001) developed distant metastases. Tumors with stage ≥IB and either ≥2 mitoses, Ki-67 >5% or loss of CD44 metastasized occasionally (11%). ConclusionAdding tumor diameter, CD44 and Ki-67 to the widely used TC/AC classification, provides a multimodal biomarker that better stratifies patients in prognostically favorable and unfavorable categories than current standards. These findings enable risk stratification allowing a tailored treatment approach for patients with bronchial carcinoid.