Analysis of papillary urothelial carcinomas of the bladder with grade heterogeneity: supportive evidence for an early role of CDKN2A deletions in the FGFR3 pathway

Abstract

Our findings show that grade heterogeneity in urothelial carcinoma is characterized by increased MIB-1 labelling, and particularly in the FGFR3 mutant pathway, with homozygous deletions of CDKN2A in low- and high-grade areas. This would suggest that CDKN2A deletion occurs prior to grade progression and supports the current convention to assign the highest grade to urothelial carcinomas with grade heterogeneity.

p53 immunohistochemistry in high‐grade urothelial carcinoma of the bladder is prognostically significant

“…Our findings are in keeping with this; although we counted any staining intensity as positive, tumours in our cohort with 50–100% of positive cells generally showed robust staining. It is of note that some previous studies evaluating p53 staining in UCa of the bladder by using standard cut‐offs did not take staining intensity into account . Also, in the ovarian cancer study by Yemelyonova et al ., 29.8% (17/57) of ovarian carcinoma cases showed a null staining pattern for p53, in contrast to our cohort of UCas, in which 14.6% showed a null staining pattern.…”

“…IHC staining for p53 has been used as a surrogate marker for mutations in TP53 , with staining in ≥10% of tumour nuclei being used as the traditional cut‐off; however, cut‐offs ranging from 20% to 50% have been reported. A similar range of cut‐offs has been used in the assessment of p53 staining in a variety of other tumours .…”

“…Comparatively, small proportions of nonsense and frameshift mutations were also identified in this group, 34 which is in keeping with previously reported data. 17,18 IHC staining for p53 has been used as a surrogate marker for mutations in TP53, with staining in ≥10% of tumour nuclei being used as the traditional cutoff; 22 however, cut-offs ranging from 20% to 50% [26][27][28][29] have been reported. A similar range of cut-offs has been used in the assessment of p53 staining in a variety of other tumours.…”

“…The mean percentage of the triplicate core results was recorded for each case. Cases were categorized as ‘positive’ or ‘negative’ by the use of 10% and 40% cut‐offs, as previously described . Cases were then alternatively classified as ‘abnormal’ or ‘wild type’.…”

“…Cases were categorized as 'positive' or 'negative' by the use of 10% and 40% cut-offs, as previously described. 19,22,27,[29][30][31] Cases were then alternatively classified as 'abnormal' or 'wild type'. Abnormal cases were those that showed a null phenotype (complete lack of staining) and those that stained at or above a variety of cut-offs (20%, 40%, 50%, 60%, 70%, and 90%).…”