الفهرس 
Urinary Bladder CarcinomaOnly 14 pages are availabe for public view
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Abstract
Urinary bladder carcinoma (UBC) represented a major global health problem. It is the ninth most common cancer worldwide. It is associated with high morbidity and mortality. In Egypt it represents 6.94% of total cancer cases according to the national population based cancer registry program.
Urothelial carcinoma originated from the bladder urothelium, an epithelial tissue with a clear hierarchical organization consisted of three morphologically distinct cell types: basal, intermediate and umbrella cells, giving representation of early, mid and later differentiated states, respectively. Malignant transformation can occur in any of these cell types thus resulting in tumors with diverse phenotypes.
We assessed the immunohistochemical expression and the prognostic impact of CK5, CK14 and CK20 with the potential to stratify bladder carcinoma into basal-like and luminal-like subtypes and to evaluate their prognostic impact.
Regarding CK5, it was expressed in 81.1% of the studied cases. The percent of expression ranged from 5 to 100 % with a mean ± SD of 36.91 ± 28.86 and a median of 25.0. Most of the positive cases showed focal positivity (61/90, 83.6%) which was mostly cytoplasmic/membrano-cytoplasmic expression (60% of the cases).
CK5 showed variable intensities with predominant strong intensity in 59%, moderate intensity in 27.3% and mild intensity in 13.7%. H-score ranged between 5 and 300 with a mean±SD of 87.26±76.40 and median of 60.
CK5 expression was associated with old patients (p=0.012), and with presence of bilharziasis (p=0.042). CK5 H score values were significantly in favor of UC cases that didn‘t receive BCG therapy (p=0.032). Strong CK5 expression was significantly in favor of cases not receiving BCG (P=0.05). CK5 H-score was significantly in favor of inflammatory stromal reaction (p=0.032) and cases with advanced stage (p=0.023). Old age was found to be associated with CK5 H-score, however the relationship was near significant (p=0.06).
CK20 was expressed focally in 47.8% of the studied cases. The pattern of CK20 positivity was cytoplasmic/membrano-cytoplasmic (C/MC) in 42% of the cases while the 58% of the cases were purely membranous. The percent of expression ranged from 5 to 95 %. CK20 H-score ranged between 0.5 and 285 with a mean ± SD of 91.64 ± 76.5 and a median of 60. CK20 showed variable intensities with predominate moderate intensity in 53.5%, strong intensity in 30.2% and mild intensity in 16.3%.
CK20 expression was significantly related to the histologic type of bladder cancer since its expression was more in pure urothelial carcinoma (40/43) (p=0.009). H score values were higher in cases with early stage (127.08 ± 77.65) in comparison with advanced stage (77.92 ± 72.71) (p=0.05). Moreover, H score values of CK20 were higher in patients receiving BCG compared to those who didn‘t receive with a near significant value (p=0.060).
None of the studied clinicopatholoical parameters favored a certain intensity in CK20 expressed urinary bladder carcinoma cases (P>0.05).
Forty six (51.1%) of the studied cases expressed CK14. Most of the positive studied cases (39/90, 84.8%) showed focal CK14 expression, while 7 (15.2%) cases showed diffuse expression. The pattern of CK 14 positivity was cytoplasmic/membrano-cytoplasmic (C/MC) in 58.7% (27/46) of the cases, while 41% (19/46) of the cases were purely membranous. The percent of expression ranged from 5 to 100 % with a mean ± SD of 38.04 ± 26.47 and a median of 32.50. H-score ranged between 10 and 300 with a mean ± SD of 90.76 ± 68.64 and a median of 75. CK14 showed predominant strong intensity in 58.7%, moderate intensity in 28.3% and mild intensity in 13.0%.
CK14 was significantly in favor of (P=0.015) perineural invasion. Strong CK 14 expression was nearly significantly (p=0.070) in favor of inflammatory stroma.
H score values of CK 14 were higher in advanced stage and in cases with absent bilharziasis compared to early stage and to those associated with bilharziasis with a significant difference (P=0.05). Furthermore, mean and median values of CK 14 were higher in pure SCC compared to other histologic types with a near significant differences (p=0.07).
By using CK5 and CK20 as surrogate markers for the basal and luminal subtypes, respectively, four subtypes of urothelial carcinomas in the current study were stratified: (i) CK5+/CK20+ group was composed of 38 cases (42%), (ii) CK5+/CK20- composed of 35 cases (39%), (iii) CK5-/CK20+ composed of 5 cases (5%) and (iv) CK5-/CK20- composed of 12 cases (13%).
The CK5+/CK20- group comprised all cases of squamous cell carcinoma, and most cases infested with bilharziasis compared to CK5+/CK20+ group which comprised mostly of urothelial carcinoma and not associated with bilharziasis.
Lymph node involvement was more in group CK5+/CK20- (44%) followed by group CK5+/CK20+ (32%) with absence of significant differences.
Immunohistochemical expression of CK5, CK14 and CK20 were used to stratify the cases into the basal differentiation subtype, defined by CK14+CK5+CK20− (19 cases), intermediate (CK14−CK5+CK20−) (16 cases), and differentiated (CK14−CK5−CK20+) subtypes (3 cases).
Basal subtype according to the above stratification showed higher mitotic index compared to intermediate group with a significant difference (P=0.011).
Old patients (P=0.001) and those associated with high CK5 H-score (P=0.075) experienced poor overall survival. On the other hand, other parameters, markers and classified subgroups failed to show any significance.