PUC is recognized as a rare and aggressive variant of UC, which often presents at a high stage and carries a poor prognosis. [3] Sahin et al. first described this tumor in 1991. [1] Mai et al. reported an incidence of 2.7% of PUC in a series of muscle invasive UC. [9] In this study, 9 of 12 tumors were invasive. Two-thirds of our PUC patients died during follow-up. The median age at diagnosis was 71 years, a finding similar to other recent reports. We recognized that the poor prognoses of these cases are due to the high invasion and the high clinical stage at presentation. [3] However, it is unclear how often PUC shows high invasion.
EMT is an important step during epithelial tumor metastasis. [10] EMT causes changes in cell-cell and cell-extracellular matrix interactions resulting in transmigration of cancer cells, thus leading to metastasis.[11] [12] E-cadherin is a cell-cell junction protein that is frequently downregulated or lost during EMT, whereas expression of N-cadherin, Vimentin, Fibronectin and Snail are acquired during this process. In this study, E-cadherin expression was largely negative, while N-cadherin, Vimentin, Fibronectin and Snail were mostly positive. The present study reported a possibility of EMT in PUC.
E-cadherin is a key structure protein in maintaining both the stability of adhesion between epithelial cells and the stability of tissues. [13] Recent studies have demonstrated that loss of E-cadherin expression may correlate with high grade and advanced stage of UC.[14] [15] Other studies reported that the majority of PUC cases show low E-cadherin expression. [3, 8] Keck et al. reported that most PUC with loss of membranous E-cadherin show a nuclear accumulation of E-cadherin. E-cadherin also serves as an independent prognostic factor for reduced overall survival of patients with muscle-invasive bladder cancer who were treated with radical cystectomy and adjuvant chemotherapy.[16] In this study, 10 of 12 cases (83.3%) showed largely negative membranous E-cadherin.
Snail is considered a key regulator of EMT and, therefore, of tumor progression. Bruyere et al. reported that Snail expression predicts tumor recurrence in superficial bladder cancer. [17] Kosaka et al. reported that Snail expression is a prognostic predictor of disease-free survival and disease-specific survival in upper urinary tract UC. [18] We also previously reported that Snail expression may predict poor outcome in bladder cancer patients treated with neoadjuvant chemotherapy.[19] In this study, Snail was mostly positive in 83.3%. PUC also may predict poor outcome by Snail. Further studies with a large cohort of PUC patients are needed to confirm this result.
Whether survival is related to the proportion of plasmacytoid variant histology has been unknown. Here we assessed the association between the proportion of plasmacytoid variant histology and survival in PUC patients. Analysis of the correlation between amount of PUC and outcome revealed that the three patients with < 10% plasmacytoid component did not die from cancer, while 88.9% of those with > 10% plasmacytoid component died from disease. This result may demonstrates the importance in identifying the amount of PUC.