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Войти в исследования Histopathology · 2026
Marked attenuation of P63 expression in plasmacytoid urothelial carcinoma with expanded immunohistochemical framework including E-cadherin, P120, HER2 and TRPS1.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Yaprak Bayrak Busra, Kosemehmetoglu Kemal, Ozbek Busra, Simsek Sercan, Oktay Murat, Coban Ganime, Arslan Kahraman Dilara Irem, Akıncıoglu Egemen, Buyukgok Melek, Colak Selin, Dogan Hatice Nese, Gurel Burak, Kabul Selva, Karaca Kerem, Ozsagir Elif, Ozturk Ece, Toru Havva Serap, Turan Gupse, Yıldırım Nazif Alperen, Yıldız Ozlem Nur, Karabulut Yasemin Yuyucu, Cheng Liang, Akgul Mahmut
Аннотация
AIMS: Plasmacytoid urothelial carcinoma (PUC) is an aggressive morphological subtype characterized by discohesive single-cell infiltration and frequent loss of epithelial adhesion. Although p63 is widely regarded as a reliable urothelial lineage marker in conventional urothelial carcinoma, its expression may be reduced or absent in plasmacytoid tumours, creating an important diagnostic pitfall. This multi-institutional study aimed to characterize the clinicopathological and immunohistochemical profile of PUC, with particular emphasis on p63 immunoreactivity and its relationship to adhesion-related markers and other diagnostically relevant immunophenotypes.
METHODS AND RESULTS: A total of 93 cases initially diagnosed as PUC were retrospectively reviewed across multiple centres. After histopathological re-evaluation, 70 confirmed cases were included. Immunohistochemical analysis was performed for p63, e-cadherin, p120 catenin, TRPS1, HER2/Neu. The cohort comprised 70 patients with a median age of 66.5 years (IQR, 59.8-72.0) and a strong male predominance of 85.7% (60/70). Most specimens were obtained from transurethral resections (64.3%, 45/70) and radical cystectomy specimens (34.3%, 24/70). The median tumour size was 3.0 cm (IQR, 1.0-5.0), and the median proportion of plasmacytoid differentiation was 80% (IQR, 20-100). Morphologically, tumours were classified as classic plasmacytoid in 65.7% (46/70), pleomorphic in 22.9% (16/70) and desmoplastic in 11.4% (8/70). Concurrent variant histology was identified in 21.4% (15/70), most commonly micropapillary (12.9%, 9/70) and sarcomatoid (7.1%, 5/70) components. Lymphovascular invasion was present in 51.4% (36/70), and concomitant carcinoma in situ was detected in 35.7% (25/70). Immunohistochemically, p63 expression was retained in only 10.0% of tumours (7/70). HER2 membranous overexpression was observed in 58.6% (41/70), while loss of E-cadherin expression was highly prevalent (84.3%, 59/70). Aberrant p120 catenin expression was common, with cytoplasmic localization in 72.9% (51/70) and complete loss in 17.1% (12/70). TRPS1 immunostaining was available in 54 tumours and was negative in 92.6% of evaluable cases (50/54).
CONCLUSION: PUC demonstrates a distinctive immunophenotype characterized by frequent loss of p63 and disruption of the e-cadherin/p120 adhesion complex. Recognition of p63 attenuation, together with adhesion-related markers and HER2 status, provides a useful diagnostic framework for distinguishing this aggressive subtype from conventional urothelial carcinoma and its mimickers.
METHODS AND RESULTS: A total of 93 cases initially diagnosed as PUC were retrospectively reviewed across multiple centres. After histopathological re-evaluation, 70 confirmed cases were included. Immunohistochemical analysis was performed for p63, e-cadherin, p120 catenin, TRPS1, HER2/Neu. The cohort comprised 70 patients with a median age of 66.5 years (IQR, 59.8-72.0) and a strong male predominance of 85.7% (60/70). Most specimens were obtained from transurethral resections (64.3%, 45/70) and radical cystectomy specimens (34.3%, 24/70). The median tumour size was 3.0 cm (IQR, 1.0-5.0), and the median proportion of plasmacytoid differentiation was 80% (IQR, 20-100). Morphologically, tumours were classified as classic plasmacytoid in 65.7% (46/70), pleomorphic in 22.9% (16/70) and desmoplastic in 11.4% (8/70). Concurrent variant histology was identified in 21.4% (15/70), most commonly micropapillary (12.9%, 9/70) and sarcomatoid (7.1%, 5/70) components. Lymphovascular invasion was present in 51.4% (36/70), and concomitant carcinoma in situ was detected in 35.7% (25/70). Immunohistochemically, p63 expression was retained in only 10.0% of tumours (7/70). HER2 membranous overexpression was observed in 58.6% (41/70), while loss of E-cadherin expression was highly prevalent (84.3%, 59/70). Aberrant p120 catenin expression was common, with cytoplasmic localization in 72.9% (51/70) and complete loss in 17.1% (12/70). TRPS1 immunostaining was available in 54 tumours and was negative in 92.6% of evaluable cases (50/54).
CONCLUSION: PUC demonstrates a distinctive immunophenotype characterized by frequent loss of p63 and disruption of the e-cadherin/p120 adhesion complex. Recognition of p63 attenuation, together with adhesion-related markers and HER2 status, provides a useful diagnostic framework for distinguishing this aggressive subtype from conventional urothelial carcinoma and its mimickers.