Data documento
26/04/2024

Título
PD L1 expression and microsatellite instability (MSI) in cancer of unknown primary site

Autor(es)
JÚNIOR, João Neif Antonio - PRETO, Daniel D.’Almeida - LAZARINI, Maria Eduarda Zanatta Neder - LIMA, Marcos Alves de - BONATELLI, Murilo - BERARDINELLI, Gustavo Noriz - SILVA, Vinicius Duval da - PINHEIRO, Céline - REIS, Rui Manuel, CÁRCANO, Flavio Mavignier -

Palavras chave
Neoplasms - Unknown primary - Microsatellite instability - Immune checkpoint proteins - Immunotherapy

Resumo
Background Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical–pathological features. Methods The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis. Results Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6–5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively). Conclusion PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.

Citação
Junior JNA, Preto DD, Lazarini MEZN, de Lima MA, Bonatelli M, Berardinelli GN, da Silva VD, Pinheiro C, Reis RM, Cárcano FM. PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site. Int J Clin Oncol. 2024 Mar 25. doi: 10.1007/s10147-024-02494-3. Epub ahead of print. PMID: 38528294.

Data documento
19/03/2025

Título
PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site

Autor(es)
João Neif Antonio Junior - Daniel D Almeida Preto - Maria Eduarda Zanatta Neder Lazarini - Marcos Alves de Lima - Murilo Bonatelli - Gustavo Noriz Berardinelli - Vinicius Duval da Silva - Céline Pinheiro - Rui Manuel Reis - Flavio Mavignier Cárcano.

Palavras chave
Immune checkpoint proteins; Immunotherapy; Microsatellite instability; Neoplasms; Unknown primary.

Resumo
Background: Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical-pathological features. Methods: The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis. Results: Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6-5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively). Conclusion: PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.

Citação
unior JNA, Preto DD, Lazarini MEZN, de Lima MA, Bonatelli M, Berardinelli GN, da Silva VD, Pinheiro C, Reis RM, Cárcano FM.Int J Clin Oncol. 2024 Jun;29(6):726-734. doi: 10.1007/s10147-024-02494-3.Epub 2024 Mar 25. PMID: 38528294