الفهرس 
INTRODUCTION
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
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Abstract
Urinary bladder cancer (UBC) is the ninth most common malignant neoplasm worldwide. It is relatively common in more developed regions and occurs among men more than in women (sex ratio worldwide is 3.5:1). In Egypt, UBC is the second most common malignancy in males and the third common cancer for both sexes combined.
The majority of newly diagnosed UBC patients are presented by non-muscle invasive bladder cancer (NMIBC).Despite NMIBC can be successfully treated by transurethral resections of bladder tumor (TURBT), it has a tendency to recur in 70-80% of cases and tumor progression occurs in approximately 10-15% of cases. Therefore, NMIBC patients require intensive surveillance after treatment, making it one of the most expensive cancers to manage. There is a precise need to find an effective, reliable, and non invasive method to select patients who are liable for more recurrence or even for aggressive tumor behavior as these patients may get benefits from adjuvant chemotherapy, immunotherapy or even early cystectomy.
UBC recurrence and progression have been explained by cancer stem cell (CSC) model or hierarchy model, which postulates that each tumor contains a biologically distinct classes of cells with differing functional abilities and behavior. This subpopulation of cells has been thought to be associated not only with tumorigenesis but also with tumor recurrence and metastasis.However, there is no sufficient evidence for putative CSCs in UBC. Better understanding of bladder CSC might be important to elucidate tumorigenesis, to analyze prognostic factors for recurrence and progression, and to establish new therapeutic approaches targeting CSCs.
Considering the important roles of two important transcription factors Octamer-binding transcription factor 4 (OCT-4), and Sex determining region Y-box 2 (SOX2) in carcinogenesis, we speculate that they may be potentially valuable biomarkers for predicting recurrence and progression in patients with NMIBC.
In the present study, we analyzed immunohistochemical expression of OCT-4 and SOX2 in NMIBC regarding its prognostic significance and relation to recurrence.
This retrospective study comprised 50 cases with primary NMIBC.
Clinical data (patient age, gender, tumor size,tumor number) were collected from the patient`s medical records from the archives of the Pathology Department, Faculty of Medicine, Alexandria University and from the archive of pathology department, Abu kir insurance specialty hospital from the period of 2010-2013.
The histological features of tumor grade, and stage were assessed on hematoxylin and eosin-stained tissue sections according to International Society of Urological Pathology (ISUP) criteria for grade and classified according to Union Internationale Contre le Cancer (UICC) TNM classification for stage according to the fourth edition of World Health Organization (WHO) classification of urogenital tumors (WHO ”blue book”), published in 2016.
The age of the cases ranged from 37 and 75 years with mean age of 52.18 years. Forty-five cases (90%) were males and five cases (10%) were female cases among the whole studied cases.
Tumor size was < 1cm in twelve cases (24%), 1-3 cm in twenty-seven cases (54%), and >3cm in eleven cases (22%).
The tumor was unifocal (involving a single site) within the urinary bladder in forty-two cases (84%) and eight cases (16%) exhibited multifocality (involving >= 2 sites).
Low grade tumors were detected in thirty cases (60%),while high grade tumors were detected in twenty cases (40%).
Tumors were classified as pTa in six cases (12%) , wherase pT1 tumors were detected in forty four cases (88%).
The present study revealed that tumor size >3cm is statistically correlated with both tumor recurrence and progression .Furthermore tumor size approaches level of significance with poor recurrence –free survival, and significantly correlated with progression free survival (follow-up period of 36 months). Potential care to cases with tumor size >3cm is mandatory such as single post-operative instillation of chemotherapy, shorter interval to second follow up that not exceed 42 days, and resection of apparently normal mucosa on the border of tumor for approximately 1 cm around tumor to exclude any malignancy as a trial to increase both the recurrence and progression free survival.
For the evaluation of immunohistochemical results, cases were classified as positive or negative for OCT-4 and SOX2 staining based on 5% cutoff value.
Of the 50 examined cases, 34 cases (68%) were positive for OCT-4.
Positive OCT-4 expression was statistically significant with high tumor grade and so it may have a role as a predictive marker for tumor progression.
No significant correlation was found between immunohistochemical expression of OCT-4 and the other clinicopathological parameters studied (age, sex, tumor size, tumor number or pathological stage (p > 0.05).
No significant correlation between OCT-4 expression and tumor recurrence or progression. Study of expression pattern of OCT-4 in different stage is recommended as in CIS, stage T2, T3,T4 to evaluate its role in UBC tumorgenesis.
Positive SOX2 expression in NMIBC was detected in 50% of cases and only 3 cases (6%) had SOX2 expression in >50% of tumor cells. Moreover no significant correlation was found between SOX2 expression and tumor number, size, grade, or stage. Furthermore no significant correlation was revealed between SOX2 expression and tumor recurrence, recurrence-free survival,progression,and progression free survival. from these data it seems that SOX2 has limited role in early stages UBC, and larger prospective studies are needed in advanced stages to precisely confirm its role in UBC.