Abstract

Objectives: The objectives of this study were to provide an outlook of urothelial carcinoma through the immunohistochemical expression patterns of octamer-binding transcription factor 4 (OCT4) in high-grade transitional cell carcinoma (TCC) of the urinary bladder.
 Methods: A total number of 60 tissue samples were collected for the study. Patients were divided into two groups according to the pathological diagnosis of the bladder tissue, Group A: 30 cases with high-grade TCC of the bladder and Group B: 30 cases with apparently normal bladder tissue. Tissue immunohistochemical analysis was applied to investigate the expression patterns of cancer stem cell (CSC) markers OCT4 in bladder samples.
 Results: OCT4 was positive in 80% of specimens of Group A and 3.3% in specimens of Group B. The association between OCT4 marker result and certain histopathological features in high-grade group: Positive OCT4 result was found in patients with inflammation and necrosis (90.9%) with a significant association (p=0.013). Regarding muscular invasion, we noticed that 87.5% of patients with muscular invasion showed positive OCT4 marker result with a significant association (p=0.039) between OCT4 marker result and muscular invasion. As well, OCT4 marker was highly sensitive and specific (sensitivity=66.7%, specificity=96.7%, and accuracy=76.7%).
 Conclusion: There was a significant expression of CSC OCT4 in high-grade TCC, OCT4 can be considered as a key regulator of tumor progression, aggressive behavior, and metastasis.

Highlights

  • IntroductionUrothelial carcinoma (transitional cell carcinoma [TCC]) of the urinary bladder represents 90% of all primary tumors of this organ, and one of the most common 10 malignancies in Iraq and worldwide

  • Urothelial carcinoma of the urinary bladder represents 90% of all primary tumors of this organ, and one of the most common 10 malignancies in Iraq and worldwide

  • There was a significant expression of cancer stem cell (CSC) octamer-binding transcription factor 4 (OCT4) in high-grade transitional cell carcinoma (TCC), OCT4 can be considered as a key regulator of tumor progression, aggressive behavior, and metastasis

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Summary

Introduction

Urothelial carcinoma (transitional cell carcinoma [TCC]) of the urinary bladder represents 90% of all primary tumors of this organ, and one of the most common 10 malignancies in Iraq and worldwide. These tumors can range from low-grade papillary neoplasm to less frequent more aggressive and invasive high-grade tumors [1]. OCT-4 is a homeodomain transcription factor of the POU family It is critically involved in the self-renewal of undifferentiated embryonic stem cells. The OCT4A form, which is present in cell nuclei, exhibits transcription factor functions and is responsible for maintaining cells at an undifferentiated stage, stem cell properties, and the ability for self-renewal. One possible mechanism responsible for the more aggressive behavior of cancers and worse clinical outcomes with cells expressing OCT4 is the presence of the stem cell phenotype in cancers related to OCT4-mediated dedifferentiation and related chemoresistance [12]

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