Prognostic Significance of CD44 and Orthopedia Hom

Authors: George Papaxoinis Daisuke Nonaka Ciara O’Brien Benjamin Sanderson Piotr Krysiak Wasat Mansoor

Publish Date: 2016/11/21

Volume: 28, Issue: 1, Pages: 60-70

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Abstract

CD44 and orthopedia homeobox protein OTP expressions have shown to be predictive of overall survival in pulmonary carcinoid PC tumours The scope of the present study was to validate their role in PC patients and investigate potential application in clinical practice Data was collected from patients presenting to a tertiary cancer centre diagnosed with PC between 2003 and 2015 Diagnosis was confirmed by central pathology review Formalinfixed paraffinembedded FFPE tissue samples collected at diagnosis were scored using immunohistochemistry H score for standard CD44 and nuclear and cytoplasmic OTP protein expression The study included 108 patients High CD44/nuclear OTP nOTP expression was strongly associated with typical carcinoid TC histology p  0001 Eightysix patients who underwent radical surgical resection were selected to assess the impact of patient and tumour parameters on relapsefree survival RFS Sixtynine 80  had TC and 17 20  had atypical carcinoid tumours On multivariate analysis high CD44 and nOTP expression TC histology and noninfiltrative tumour growth were associated with superior RFS Early stage TC stage pT1aN0 patients N = 32 46  had excellent prognosis irrespective of CD44/nOTP status Importantly TC patients with locally advanced disease defined as pT1aN0 and high CD44/nOTP expression N = 26 38  had excellent RFS p = 0005 compared to those with the same stage but low CD44 and/or nOTP N = 11 16  Additionally the combination of CD44/nOTP expression and tumour growth pattern led to a more accurate prognostic system compared to the established WHO classification of PC tumours concordance index = 0902 vs 0811 respectively p  0001 Assessment of CD44/nOTP expression combined with tumour growth pattern identifies clear groups with largely different prognosis These findings provide important information on how patients with these resected cancers should be followed up

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