Risk factors and therapeutic significance of HER2 overexpression in urothelial carcinoma.

OBJECTIVE

We analyzed the expression of HER2 in urothelial carcinoma (UC) and the risk factors for overexpression, and then further explored the guiding significance of HER2 in the treatment of locally progressive and advanced UC.People's Republic of China METHODS: Immunohistochemistry (IHC) was used to detect HER2, luminal markers (CK20, GATA3), and basal markers (CK5/6, CD44). HER2 overexpression was defined as IHC 2 + or IHC 3 + . Binary logistic regression was used to analyze the risk factors for HER2 overexpression. The therapeutic significance of HER2 was preliminarily discussed through case analysis.

RESULTS

A total of 119 patients with UC were included in this study, including 99 males and 20 females, with an average age of 66.2 ± 9.6 years. UC were derived from the bladder [n = 97 (81.5 %)], renal pelvis [n = 15 (12.6 %)], ureter [n = 6 (5.0 %)] and prostate [n = 1 (0.8 %)], respectively. UC were classified according to molecular typing into luminal 76 (63.9 %) cases and basal 29 (24.4 %) cases. HER2 expression rates of IHC 0, 1 + , 2 + , and 3 + in UC were 39.5 %, 23.5 %, 31.9 %, and 5 %, respectively. HER2 overexpression was as high as 52.6 % in luminal patients, but only 3.4 % in basal patients (53.2 % vs 3.4 %, P < 0.001). HER2 overexpression was strongly correlated with lower urinary tract, invasive, high-grade, multiple tumors and luminal (P < 0.05), while no significant correlation was seen with patients' gender (P = 0.311), age (P = 0.722), lymph node metastasis (P = 0.282) and ki67 index (P = 0.964). Multiple tumors (OR=5.346, 95 %CI: 1.921-14.877, P = 0.001) and luminal (OR=28.827, 95 %CI: 2.768-300.225, P = 0.005) were independent risk factors for HER2 overexpression. cT2N0M0 patient with HER2 (2 +) showed significant tumor shrinkage after preoperative neoadjuvant therapy with RC48-ADC.

CONCLUSIONS

HER2 testing can be routinely done in patients with locally advanced or metastatic UC, multiple tumors and luminal. Neoadjuvant therapy (HER2-ADC) for locally advanced UC was found to significantly shrink tumors, providing a theoretical basis for organ preservation and functional protection in genitourinary tumor surgery. HER2-ADC may be effective and safe in the treatment of locally progressive or advanced UC.