The effect of GATA3, P53, Kİ-67 and CD44 expressions on recurrence and progression in non- muscle invasive bladder cancer that receiving intravesical BCG immunotherapy

The patients with bladder cancer apply to the urology clinics generally at the stage of non-muscle invasive bladder cancer (NMIBC). Intravesical Bacillus Calmette-Guérin (BCG) treatment is given as a standard treatment in the appropriate patients. The high rates of recurrence and progression suggest that these tumors should be followed more closely and early radical treatment should be considered for proper patients. For this purpose, we evaluated p53, Ki-67, CD44 and, GATA3 molecules, which are markers that can predict the risk of recurrence and progression along with clinical and histopathological factors in patients receiving intravesical BCG therapy. The patients (n=240) who received intravesical BCG therapy for NMIBC between 2009-2020 in the Urology Clinic of Tekirdağ Namık Kemal University were analyzed retrospectively. The patients (n=106) who met the inclusion and exclusion criteria were included in the study. These patients were divided into 3 groups as fully responding to intravesical BCG therapy, recurring despite BCG therapy, and progressing despite BCG therapy. The pathologies of these patients were evaluated again by a single uropathologist in terms of p53, Ki-67, CD44 and, GATA3 expressions by immunohistochemical (IHC) analysis. In the IHC examination, the score was 0: 0-10% staining, the score 1: 10-25% staining, the score 2: 25-50% staining, the score 3: 50-75% staining, and the score 4: more than 75% staining. IHC expression positivity; the cutoff value was accepted as 25% for p53 and Ki-67, and 50% for GATA3 and CD44. Expressions of p53, Ki-67, CD44 and, GATA3 were evaluated in terms of recurrence and progression in patients receiving intravesical BCG therapy. When we evaluated the patients; 97 (91.5%) of the patients were male, 9 (8.5%) were female, and the mean age was 65±11 years. A complete response to intravesical BCG treatment was observed in 71 (67%) patients, tumor recurrence was found in 28 (26.4%) patients, and tumor progression was found in 7 (6.6%) patients. When the patients were evaluated in terms of recurrence, no significant difference was found in terms of age, gender, tumor number, grade, and stage. However, recurrence was found to be high in patients with tumor sizes larger than 3 cm (p=0.004). In addition, recurrence was found to be higher in GATA3 negative patients (p<0,001). When the patients are evaluated in terms of progression; there was no significant difference in terms of age, gender, tumor size, number, grade, and stage. In patients who received intravesical BCG therapy, progression was significantly higher in p53 positive, Ki-67 positive, and GATA3 negative patients, respectively (p=0.034), (p=0.017), (p<0,001). While there was no significant relationship between CD44 expression evaluated by IHC analysis and tumor recurrence and progression in patients receiving intravesical BCG therapy, high p53, and Ki-67 expression were found to be important in progression. It was also observed that low GATA3 expression could predict recurrence and progression in this patient group. As a result of IHC analysis, it may be appropriate to direct high p53 and Ki-67 expression and low GATA3 expression to earlier radical curative treatments. Key words: GATA3, CD44, p53, Ki-67