الفهرس 
Molecular classification of urothelial carcinomaOnly 14 pages are availabe for public view
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Abstract
Urinary bladder cancer (UBC) is the 9th most common cancer worldwide and the 7th most common worldwide in men. The majority (90%) of bladder cancer consists of urothelial carcinoma as the predominant histologic type. In Egypt, bladder cancer is the most prevalent malignancy among Egyptian males (16%), producing >7900 deaths annually, which is strikingly higher than most other parts of the world.
The aim of this study is to investigate the expression of GATA3 and CK5/6 in bladder urothelial carcinoma with correlation to clinicopathologic and prognostic parameters including their impact on survival beside their potential use to stratify cases into prognostic subgroups.
Using the standard IHC technique, we assessed GATA3 and CK5/6 expressions in 80 primary bladder carcinoma specimens that include 41 radical cystectomies (37 were muscle invasive and 4 were non muscle invasive bladder cancer) and 39 TURBT biopsies (36 were non muscle invasive and 3 were muscle invasive bladder cancer). The cases were retrieved from the archives of Pathology Department, Faculty of Medicine, Menoufia University spanning the period between January 2016 and September 2019.
In the current study, 69 cases of 80 studied primary bladder carcinoma cases were males (86.2%) and 11 were females (13.8%) with a male to female ratio of 6.3:1. The age ranged from 26 to 84 years with a mean of 63.23 years.
All the investigated cases were urothelial carcinoma either pure or with squamous differentiation and most of them (86.2%) were of high grade. Regarding the TNM stage, 50% of studied cases were non-muscle invasive (Ta, T1), 50% were muscle invasive (T2, 3, 4) and 31.7% (13/41) had LN invasion.
As regards GATA3, its expression was detected in 85% of the studied cases. Increased GATA3 percentage of positivity, IRS and H-score showed significant association with pure urothelial carcinoma (P= 0005, 0.037 and 0.006, respectively), non-muscle invasion (P< 0.001, 0.024 and 0.004, respectively), low mitotic count (P= 0.013, 0.005 and 0.014, respectively), inflammatory stromal reaction (P= 0.001, 0.006 and 0.005, respectively) and absence of perineural invasion (P= 0.006, 0.033 and 0.028, respectively). High GATA3 percentage of positivity was associated with absence of bilharziasis (P= 0.044) and absence of LVI (P= 0.014).
As regards CK5/6, its expression was detected in 32.5% of the studied cases. CK5/6 positivity showed significant association with urothelial tumors with squamous differentiation (P = 0.001) and presence of perineural invasion (P = 0.05). CK5/6 positivity and high IRS were associated with muscle invasion (P= 0.001 and 0.007, respectively) and presence of necrosis (P = 0.003 and 0.006, respectively).
Stratification of the studied cases (80 cases) depending on immunoreactivity for GATA3 and CK5/6 expression revealed four groups, mixed (25%), luminal (60%), basal (7.5%) and null group (7.5%). Basal group was significantly associated with urothelial tumors with squamous differentiation (P = 0.012) and with muscle invasive tumors (P = 0.05). On the other hand, luminal group was associated with pure urothelial carcinoma and non-muscle invasive tumors.
Stratification of non-muscle invasive tumors (40 cases) showed that basal tumors was associated with presence of bilharziasis (P = 0.02).
In the present study, presence of bilharziasis showed significant association with short progression free survival (PFS) (P = 0.04). However, GATA3, CK5/6 and stratified subgroups showed no impact on patient’s OS and PFS.