Sarcomatoid carcinoma of the upper urinary tract: clinical outcome and molecular characterization

Sarcomatoid carcinoma (carcinosarcoma) of the upper urinary collecting system is a rare aggressive malignancy composed of malignant epithelial and stromal components. Because of the paucity of reported cases, the clinical behavior, molecular alterations, and potential therapies for this malignancy are not well understood. Eight cases of sarcomatoid carcinoma involving the upper urinary tract were studied. Clinicopathologic characteristics were reviewed. Immunohistochemical expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2)/neu, c-kit, and p53 was analyzed in each case. Evaluation for amplification of EGFR and HER2 genes was performed by interphase fluorescence in situ hybridization (FISH). Each tumor was also examined for gains of chromosomes 3, 7, and 17 and for loss of chromosome 9p21 by UroVysion FISH (Vysis, Downers Grove, IL). The patients we studied were 5 females and 3 males, ranging in age from 56 to 78 years (mean age, 69 years). Presenting symptoms included gross hematuria, flank mass, urinary obstruction, fever, or sepsis. Radical nephroureterectomy was performed on all patients. Tumor size ranged from 2 to 13 cm. Coexisting urothelial carcinoma was present in all 8 cases. Heterologous osteosarcoma was identified in 2 cases. Pathologic stage was pT4 in 5 cases and pT3 in 3 cases. Lymph node metastases were present in 5 patients at the time of surgery. Of 8 patients, 7 died within 2 years after surgery. EGFR immunostaining had moderately to strongly positive results in 6 of 8 cases. Both HER2/neu and c-kit immunostaining had negative results in all cases. p53 immunostaining had positive results in 5 of 8 cases. The EGFR polysomy was demonstrated in 7 of 8 cases. No amplification of HER2/neu was present in any case. UroVysion FISH showed abnormalities typical of urothelial carcinoma in all 8 cases. In conclusion, the prognosis of sarcomatoid carcinoma of the upper urinary tract is extremely poor, most patients died within 2 years (7/8 patients). Gains of chromosome 3, 7, and 17 and loss of chromosome 9p21 were commonly observed in these tumors. Our findings suggest that targeted therapy may be a rational strategy in the management of these patients.