Publications

Authors:

Brunelli, Matteo; Gobbo, Stefano; Malpeli, Giorgio; Sirgiovanni, Grazia; Caserta, Claudia; Munari, Enrico; Francesconi, Simona; Caliò, Anna; Martignoni, Guido; Cimadamore, Alessia; Veccia, Alessandro; Antonelli, Alessandro; Tucci, Marcello; Pierconti, Francesco; Hattab, Isabelle Malak; Eccher, Albino; Ascani, Stefano; Milella, Michele; Buffoni, Lucio; Cheng, Liang; Bracarda, Sergio

Title:

TROP-2, NECTIN-4 and predictive biomarkers in sarcomatoid and rhabdoid bladder urothelial carcinoma

Year:

2024

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

PATHOLOGICA

ISSN of journal:

1591-951X

N° Volume:

116

Number or Folder:

1

Page numbers:

55-61

Keyword:

bladder, biomarker, TROP-2, NECTIN-4, urothelial carcinoma

Short description of contents:

Introduction: The surface protein TROP-2/TACSTD2 and the cell adhesion protein NECTIN-4/NECTIN4 are responsible for the efficacy of anticancer therapies based on antibody-drug conjugates (ADC) targeting intracellular microtubules. In contrast with common histologic subtypes of bladder urothelial carcinoma (BUC), little is known of TROP-2 and NECTIN-4 expression in sarcomatoid and rhabdoid BUC. Aims: In this study, we aimed to analyze TROP-2 and NECTIN-4 expression and additional predictive biomarkers by immunohistochemistry and fluorescence in situ hybridization (FISH) on 35 undifferentiated BUC (28 sarcomatoid and 7 rhabdoid). Wide genomic investigation was also performed on 411 BUC cases of the PanCancer Atlas, focusing on genes related to the microtubule pathways. Results: Seven of 35 (20%) undifferentiated BUC showed expression of TROP-2. NECTIN-4 was expressed in 10 cases (29%). Seven cases (20%) co-expressed TROP-2 and NECTIN-4. HER-2 FISH was amplified in 5 cases (14%) while HER-2 immunoexpression was observed in 14 cases (40%). PD-L1 scored positive for combined proportion score (CPS) in 66% of cases and for tumor proportion score (TPS) in 51% of cases. Pan-NTRK1-2/3 was elevated in 9 cases (26%) and FGFR-2/3 was broken in 7 of 35 cases (20%). Of 28 sarcomatoid BUC, 9 (32%) were negative for all (TROP-2, NECTIN-4, PD-L1, HER-2, FGFR and pan-NTRK) biomarkers and 3 (11%) expressed all five biomarkers. Among cases with rhabdoid dedifferentiation, 1 of 7 (14%) showed activation of all biomarkers, whereas 2 of 7 (28%) showed none. The mRNA analysis identified microtubule-related genes and pathways suitable for combined ADC treatments in BUC. Conclusion: Sarcomatoid and rhabdoid BUC do harbor positive expression of the ADC targets TROP-2 or NECTIN-4 in a relatively modest subset of cases, whereas the majority do not. Different combinations of other positive biomarkers may help the choice of medical therapies. Overall, these findings have important clinical implications for targeted therapy for BUC.

Product ID:

138565

Handle IRIS:

11562/1122033

Last Modified:

September 29, 2024

Bibliographic citation:

Brunelli, Matteo; Gobbo, Stefano; Malpeli, Giorgio; Sirgiovanni, Grazia; Caserta, Claudia; Munari, Enrico; Francesconi, Simona; Caliò, Anna; Martignoni, Guido; Cimadamore, Alessia; Veccia, Alessandro; Antonelli, Alessandro; Tucci, Marcello; Pierconti, Francesco; Hattab, Isabelle Malak; Eccher, Albino; Ascani, Stefano; Milella, Michele; Buffoni, Lucio; Cheng, Liang; Bracarda, Sergio, TROP-2, NECTIN-4 and predictive biomarkers in sarcomatoid and rhabdoid bladder urothelial carcinoma «PATHOLOGICA» , vol. 116 , n. 1 , 2024 , pp. 55-61

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