Immunohistochemical characterization of urothelial carcinoma

Abstract

From the archive of BB Biocyt company, 32 urinary bladder carcinomas (urothelium carcinomas, UC) and 7 cases of chronic cystitis were selected and examined in semiserial sections for the following antigens: 1) cell proliferation marker Ki-67 (expressed in the nuclei), 2) cell cycle regulator p16/INK4a polypeptide (expressed in the cytoplasm and nuclei), 3) urothelium marker p63 (expressed in the nuclei), 4) cytokeratin 7 (CK7). 5) cytokeratin 20 (CK20) and 6) high molecular weight cytokeratin (HMWCK). Invasive urothelium carcinomas showing a high grade dysplasia (invasive HG UC) comprised over the half (20 out of 32) of the investigated tumours. Microinvasion to lamina propria (seen in three HG papillary carcinomas) was regarded as an early infi ltration even when the position of muscular layer could not be determined. Classical invasion across the urinary bladder wall and/or to surrounding tissues was found in 17 cases of low-differentiated HG UCs. The rest (9 out of 32 neoplasms) were either non-invasive papillary carcinomas of high (non-invasive HG UC, 5 cases) or low malignant potential (noninvasive LG UC, 4 cases). Finally, 3 cases were papillary urothelium neoplasms of low malignant potential (PUNLMP). HMWCK was present in all invasive tumours, whereas the frequency of other urothelium markers ranged from 65 to 88 %. Nevertheless, at least two markers were expressed in each invasive tumour. Staining for Ki-67 antigen was positive in over 50 % of the nuclei of HG UCs, while in the LG UCs, the frequency of positive Ki-67 staining did not exceed 25 %. In PUNLMP, the positive rate of Ki-67 stained dysplastic cells was below 10 %. The staining for p16 antigen did not correlate with the degree of dysplasia within urothelium tumours. For routine diagnostic, we recommend to combine the Ki-67 staining with detection of HMWCK. In cases of chronic cystitis, which developed urothelial hyperplasia and/or squamous metaplasia, the presence of p63 antigen was a relevant marker confi rming the urothelial origin of the altered transitional cells (Tab. 6, Fig. 4, Ref. 69)

Identification of Significant Prognostic Tissue Markers Associated with Survival in Upper Urinary Tract Urothelial Carcinoma Patients Treated with Radical Nephroureterectomy: A Retrospective Immunohistochemical Analysis Using Tissue Microarray

“…Tissue microarray (TMA) of surgical specimens, and the expression of immunohistochemical tissue markers, may provide important clues to better understand the pathogenetic characteristics of UTUC and identify universal prognostic markers, which will aid in estimating more precise prognoses of UTUC after surgery. Therefore, in this study, 27 potential urothelial carcinoma-related tissue markers from previous urothelial carcinoma-related tissue studies and National Cancer Center bladder cancer panel [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] were applied immunohistochemically (IHC) to the TMA of specimens from patients with UTUC who underwent RNU, in order to identify any significant prognostic tissue markers of survival, including intravesical recurrence-free survival (IVRFS), disease-free survival (DFS), and overall survival (OS).…”

Fibroblast growth factor receptor 1 and cytokeratin 20 expressions and their relation to prognostic variables in bladder cancer

“…Alsheikh et al (2001), Pu et al (2008) and van Oers et al (2007) confirmed the association of CK20 with advanced stage and grade. Rajcani et al, (2013) found that CK20 was present in all invasive tumors. Ye et al, (2010) demonstrated that the intensity of CK20 and Ki-67 staining in cancerous tissues was significantly associated with tumor grades and distant metastasis of cancer bladder.…”

“…The expression pattern is altered only in malignant urothelium (Alsheikh et al, 2001;Southgate et al, 1999). Previous studies indicated that CK20 may be a specific biomarker for detecting bladder cancer (Rajcani et al, 2013;Eissa and Matboli, 2013;Schmidt et al, 2016).…”

Evaluation of different p16 immunostaining methods and the prognostic role of p16/Ki-67 combined expression in non-muscle invasive bladder cancers

“…In some of these studies, p16 was evaluated using a score of 0 to 3 (no staining: score 0, staining between 0 and 10%: score 1, staining between 10 and 49%: score 2, strong staining: score 3) [8,17]. In other studies, expression below 10% was regarded as abnormal, while that above 10% was considered normal [18][19][20].…”

“…P16a: p16 nuclear staining percentage was scored between 0 and 3 as follows: no expression: score 0, expression between 0 and 10%: score 1, expression between 10% and 49%: score 2, and strong expression, over 50%: score 3 [8,17].…”