Biomarker p-120 Catenin Distinguishes Conventional Urothelial Carcinoma from Variants

Initially, PC-UC was identified based on morphology as a potential mimicker of malignant plasma cell and lymphoid neoplasms and is characterized by loss of E-cadherin (E-Cad)–mediated intercellular adhesion.

Sarcomatoid UC, is another rare and aggressive variant of UC that includes carcinomatous and sarcomatous components (i.e., dedifferentiated carcinoma). The latter can be represented by a nondescript high-grade spindle cell proliferation and/or it can demonstrate more lineage-specific change, including, but not limited to, leiomyosarcomatous, rhabdomyosarcomatous, and chondrosarcomatous differentiation.

Pathologists at the Brigham and Women's Hospital (Boston, MA, USA) included in a study included a total of 58 samples from 55 patients, as three cases had areas of both PC-UC and SUC. The final breakdown included 25 conventional invasive UCs, 22 PC-UCs, six SUCs, and five micropapillary UCs. Specimen types included 45 transurethral resections/bladder biopsies, three cystoprostatectomies, one anterior pelvic exenteration, one abdominoperineal resection, two biopsies of tumor from metastatic sites (one pelvic soft tissue nodule and one peritoneal nodule), one nephroureterectomy, one penectomy, and one autopsy case.

The team performed immunohistochemistry with the Envision Plus/horseradish peroxidase system (Dako Agilent, Carpinteria, CA, USA), a polyclonal antibody to p-120 (BD Biosciences, San Jose, CA, USA), and monoclonal antibodies against E-Cad (Dako Agilent,) and B-Cat (BD Biosciences). Following Tris-buffered saline rinses, the tissues were incubated with the Envision Plus or Novolink Polymer Detection system (Leica Biosystems, Buffalo Grove, IL, USA). Eight PC-UC cases had molecular characterization via the OncoPanel assay developed at the institution.

The scientists reported that E-cadherin, B-Cat, and p-120 showed membranous staining in all conventional and micropapillary UCs. In contrast, most PC-UCs were negative for E-Cad (17/22; 77%) with an additional 2/22 cases (9%) showing cytoplasmic with partial membranous staining. p-120 catenin demonstrated cytoplasmic or negative staining in 21/22 cases (95%). Most SUCs showed an absence of E-Cad (5/6; 83%) and cytoplasmic or negative p-120 in 5/6 cases (83%). Staining for B-Cat was also abnormal in a subset of PC-UCs and SUCs. Five PC-UC cases that harbored CDH1 gene variants were p-120 cytoplasmic positive.

The authors concluded that p-120 catenin is a useful adjunct biomarker to E-Cad in the clinically important distinction of PC-UC and SUC from conventional UC. In particular, the combination of cytoplasmic p-120 and loss of E-Cad is strongly supportive of PC-UC and SUC. The study was published on August 21, 2021 in the journal Archives of Pathology and Laboratory Medicine.

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