Develop a novel method for the urinary diagnosis of urothelial carcinoma

Abstract

Urothelial carcinoma (UC) is one of the most fatal cancer in the world and the American Cancer Society has reported that bladder cancer is the fourth most common cancer among men UC includes two subtypes: muscle invasive urothelial carcinoma (MIUC; T2-T4) and non-muscle invasive urothelial carcinoma (NMIUC; Tis Ta T1) NMIUC occupies most of UC and has high recurrence rate of up to 70% Therefore NMIUC patients need regular surveillance The gold standard of clinical diagnoses of UC is cystoscopy which is an invasive and expensive method The other diagnostic methods are non-invasive including urinary cytology and biomarkers detection Papanicolaou (Pap) stain is widely used in cytology with high specificity but low sensitivity to detect low-grade UC and requirement of pathological experts to clarify malignant cells by their morphological characteristics In the present study we performed a novel cytological stain called CellDetect? which could highlight malignant cells through their color discrimination In comparison with the tissue biopsy of twenty-eight UC patients the sensitivity positive predictive value and negative predictive values of CellDetect? stain were better than those of Pap stain We suggest that the CellDetect? stain might be a promising method to develop an automatic detector to screen urinary UC cells It might promote the diagnostic efficiency and reduce the burden of pathologists On the other hand the sensitivity and specificity of urinary biomarkers even though the FDA approved biomarkers are not good for clinical detection so far Thus we wanted to develop a novel useful biomarker in the urinary detection of UC CUB domain-containing protein 1 (CDCP1) is a type I transmembrane glycoprotein which highly expresses in various cancers such as lung breast colon kidney cancers etc We evaluated tissue arrays containing 103 cases for expression of CDCP1 in tumors compared with normal urothelium tissues by IHC staining The results showed that CDCP1 was overexpressed in UC patients and associated with tumor grade with highly statistical significance It indicates that CDCP1 might be a useful biomarker in the urinary detection of UC As we analyzed several cases of UC patients we found out that if a patient had at least five trivalent malignant cells in CDCP1 IHC staining the patient would cause higher probability of having UC The applications of CDCP1 in urinary cytology of UC will improve the diagnostic efficiency of the method

Date of Award	2016 Aug 30
Original language	English
Supervisor	Huei-Sheng Huang (Supervisor)