Ubiquitin carboxy-terminal hydrolase L1 may be involved in the development of mammary phyllodes tumors

Abstract

Phyllodes tumors (PTs) are characterized by co-proliferation of the stroma and epithelium, with the stroma being the neoplastic element. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally considered to be a neuronal-specific marker, but later reports have shown both tumorigenic and antitumorigenic roles for UCHL1. Although a role for UCHL1 has been explored in many cancers, a study on PTs has never been reported. We assessed UCHL1 expression in 49 cases of PTs and 16 fibroadenomas using immunohistochemistry and examined associations with clinicopathological features. In normal breast, strong staining for UCHL1 was consistently observed in the nerve bundles, if present, in breast stroma. Scattered stromal cells showed negative to weak staining. The ductal and lobular units, in contrast, showed no staining. In contrast to the 16 fibroadenomas, of which only 3 showed mild staining, UCHL1 expression was consistently observed in all 49 PTs. There was a significantly increasing trend of UCHL1 expression with increasing PT grade (P < 0.001); strong staining was observed in 24 % of benign PTs, but was present in 56 and 90 % of borderline and malignant PTs, respectively. Consistently, UCHL1 was focally positive in regions of benign to borderline malignancy, but strongly and diffusely immunoreactive in regions of malignancy in cases of malignant PTs. In addition to PT grade, UCHL1 expression correlated with increasing stromal atypia (P = 0.01), but not with other clinicopathological parameters. In conclusion, the consistent expression of UCHL1 in PTs and an increasing trend of UCHL1 expression with an increasing PT grade suggest a role for UCHL1 in the pathogenesis and malignant progression of PTs.

Mutational analysis of MED12 exon 2 in a spectrum of fibroepithelial tumours of the breast: implications for pathogenesis and histogenesis

“…Although mostly a localized lesion, a small portion of PTs, particularly malignant PTs, behave aggressively and can metastasize similarly to a sarcoma . Although the overexpression of several markers in PTs has suggested the potential aetiological roles of pathway dysregulation involving these markers, conclusive evidence regarding the pathogenesis of PTs is limited . Fibroadenomas (FAs) and PTs are the two main prototypes of fibroepithelial tumours.…”

Mass Spectrometry-Based Quantitative Proteomic Profiling of Human Pancreatic and Hepatic Stellate Cell Lines

“…L-lactate dehydrogenase A (LDHA) is involved in tissue breakdown and turnover, which has been shown to be elevated in cancer cells, including those of pancreatic cancer [44]. In addition, ubiquitin carboxy-terminal hydrolase L1 is a deubiquitinating enzyme highly specific to neurons [45] and has a role in tumor development [46], however, its role in pancreatic and hepatic disease remains undetermined. These proteins may be investigated further to study their involvement in the pathophysiology of pancreatic and/or hepatic disease.…”