RESUMO
Desmoid tumors (DTs) are local aggressive neoplasms, whose therapeutic approach has remained so far unsolved and in many instances controversial. Nowadays, immunotherapy appears to play a leading role in the treatment of various tumor types. Characterization of the tumor immune microenvironment (TME) and immune checkpoints can possibly help identify new immunotherapeutic targets for DTs. We performed immunohistochemistry (IHC) on 33 formalin-fixed paraffin-embedded (FFPE) tissue sections from DT samples to characterize the TME and the immune checkpoint expression profile. We stained for CD3, CD4, CD8, CD20, FoxP3, CD45RO, CD56, CD68, NKp46, granzyme B, CD27, CD70, PD1 and PD-L1. We investigated the expression of the markers in the tumoral stroma, as well as at the periphery of the tumor. We found that most of the tumors showed organization of lymphocytes into lymphoid aggregates at the periphery of the tumor, strongly resembling tertiary lymphoid organs (TLOs). The tumor expressed a significant number of memory T cells, both at the periphery and in the tumoral stroma. In the lymphoid aggregates, we also recognized a significant proportion of regulatory T cells. The immune checkpoint ligand PD-L1 was negative on the tumor cells in almost all samples. On the other hand, PD1 was partially expressed in lymphocytes at the periphery of the tumor. To conclude, we are the first to show that DTs display a strong immune infiltration at the tumor margins, with formation of lymphoid aggregates. Moreover, we demonstrated that there is no PD-L1-driven immune suppression present in the tumor cells.
Assuntos
Antígeno B7-H1/fisiologia , Fibromatose Agressiva/imunologia , Tolerância Imunológica , Adolescente , Adulto , Idoso , Antígenos CD20/análise , Ligante CD27/análise , Feminino , Fibromatose Agressiva/patologia , Humanos , Antígenos Comuns de Leucócito/análise , Masculino , Pessoa de Meia-Idade , Microambiente Tumoral , Adulto JovemRESUMO
CONTEXT.: Errors in laboratory medicine could compromise patient safety. Good laboratory practice includes identifying and managing nonconformities in the total test process. Varying error percentages have been described in other fields but are lacking for molecular oncology. OBJECTIVES.: To gain insight into incident causes and frequency in the total test process from 8 European institutes routinely performing biomarker tests in non-small cell lung cancer and colorectal cancer. DESIGN.: All incidents documented in 2018 were collected from all hospital services for pre-preanalytical entries before the biomarker test, as well as specific incidents for biomarker tests. RESULTS.: There were 5185 incidents collected, of which 4363 (84.1%) occurred in the pre-preanalytical phase (all hospital services), 2796 of 4363 (64.1%) related to missing or incorrect request form information. From the other 822 specific incidents, 166 (20.2%) were recorded in the preanalytical phase, 275 (33.5%) in the analytical phase, and 194 (23.6%) in the postanalytical phase, mainly due to incorrect report content. Only 47 of 822 (5.7%) incidents were recorded in the post-postanalytical phase, and 123 (15.0%) in the complete total test process. For 17 of 822 (2.1%) incidents the time point was unknown. Pre-preanalytical incidents were resolved sooner than incidents on the complete process (mean 6 versus 60 days). For 1215 of 5168 (23.5%) incidents with known causes a specific action was undertaken besides documenting them, not limited to accredited institutes. CONCLUSIONS.: There was a large variety in the number and extent of documented incidents. Correct and complete information on the request forms and final reports are highly error prone and require additional focus.