HER2 / neu Overexpression in Urothelial Carcinoma and Its Association with Tumour Grading - A Cross Sectional Study from a Tertiary Care Hospital in Kerala

Abstract

BACKGROUND Human epidermal growth factor receptor-2 HER2 / neu, is a trans membrane tyrosine kinase receptor of epidermal growth factor receptor (EGFR) family and is involved in the pathogenesis of urinary bladder cancer. In this study we attempted to evaluate the HER2 / neu expression in urothelial carcinoma of bladder and its association with tumour grading. METHODS This was a cross sectional study with a sample size of 75. Routine 4 micrometre thick sections of formalin fixed paraffin embedded tissue blocks stained with haematoxylin & eosin were reviewed. Tumour grade was determined by using the World Health Organization (WHO) / International Society of Urological Pathologist criteria (ISUP). Immunohistochemistry was done by using HER2 / neu monoclonal antibody and its expression were observed. The membrane staining intensity and pattern were studied and scored. RESULTS In our study 75 cases of urothelial carcinoma were studied, of which 49 cases were papillary urothelial carcinoma low grade, 26 cases were papillary urothelial carcinoma high grade. Among these, 19 cases were infiltrating urothelial carcinoma. HER2 / neu positivity were observed in 27 (36 %) cases and overexpression in 8 (10 %) cases. Low grade urothelial carcinoma showed HER2 / neu positivity in 11 (22 %) cases and overexpression in 1 (2 %) case. High grade urothelial carcinoma showed HER2 / neu positivity in 16 (64 %) cases, among which 7 (28 %) cases showed overexpression. HER2 / neu positivity was seen in 13 (68 %) cases of infiltrating urothelial carcinoma with 4 (21 %) cases showing overexpression. A statistically significant difference in HER2 / neu expression was noted in high grade and invasive urothelial carcinoma compared to low grade and non-invasive urothelial carcinoma. CONCLUSIONS Urothelial carcinomas show overexpression of HER2 / neu and this over expression increases with increasing grade of tumour and muscle invasiveness. KEYWORDS Urothelial Carcinoma, HER2 / neu, Overexpression, Tumour Grade, Trastuzumab

Study of her2/neu and ki-67 expression in invasive urothelial carcinoma of bladder and their correlation with grade and stage

“…In our study, 52% cases showed positive HER2/neu expression, which was significantly associated with high grade (p<0.00001) and higher stage (pT2/pT3/pT4) (p=0.0005); such that 80% of low grade tumours showed negative HER2/neu expression and 73.3% of high grade tumours showed positive HER2/neu expression; 61.1% of pT1 tumours showed negative HER2/neu expression and 85.7% of higher stages showed positive HER2/neu expression. This is supported by Nedjadi et al, Kumar M et al, and Asmi et al 4,16,21 in contrast to Kumar S et al where no correlation was found between HER2/neu expression and tumour grade and stage. 22 In our study, 56% of 75 IUBC cases, showed high Ki-67 score, which was significantly associated with high grade (p<0.00001) and high tumour stage (p<0.0001) such that 86.7% of high grade tumours showed high Ki-67 index and 90% of low grade tumours showed low Ki67 index; 61.1% of pT1 showed low Ki-67 index and 100% of higher stages showed high Ki-67 index.…”

“…1 According to recent reports of the National Cancer Registry Programme, the overall incidence of bladder cancer in India is 2.25% (per 100,000 annually), 3.67% in males and 0.83% in females. 4 Infiltrating urothelial carcinoma is the most common malignancy of the urinary tract. The defining histological criterion is invasion beyond basement membrane: 3 beyond: pT1 tumours are treated with Transurethral resection of bladder tumours (TURBT) ± intravesical BCG immunotherapy.…”