High expression of indoleamine 2,3-dioxygenase in the tumour is associated with medullary features and favourable outcome in basal-like breast carcinoma
Medullary breast cancer (MBC) is a basal-like breast carcinoma (BLBC) with a favourable outcome, whereas nonmedullary BLBC has a poor prognosis. Tumour infiltrating lymphocytes (TILs) are present in both MBC and BLBC. We hypothesized that the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) could modulate the TILs effects among these tumours and explain their different outcomes. The amount of TILs and IDO expression were analysed using immunohistochemistry (IHC) in 155 BC cases including MBC (n = 17), atypical MBC (n = 13) and non-MBC (n = 125). Messenger RNA expression of the INDO gene, which encodes IDO, was measured in 262 cases from our institution. INDO mRNA expression and histoclinical data of 1,487 BC cases were collected from public databases. IDO immunostaining was present in both neoplastic and stromal cells in 100% of MBC and was associated with histological medullary features among non-MBC cases. There was a significant correlation between IDO positivity and TIL amounts. In our series including mostly grade-3 BC, IDO immunostaining was the most significant marker (p = 0.02) associated with better survival in multivariate analysis. Among our 262 analysed BC cases, INDO mRNA showed significant overexpression in BLBC as compared to luminal A tumours, and in MBC as compared to basal-like non-MBC. In the pooled series of 1,749 BC cases, INDO mRNA was overexpressed in BLBC and was the most significant predictor of better survival in this subtype using multivariate analysis (p = 0.0024). In conclusion, high IDO expression is associated with morphological medullary features and has an independent favourable prognostic value in BLBC.
Affiliations
INSERM & Institut Paoli-Calmettes, Marseille, FranceDépartement d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille; INSERM UMR89; IFR137, Marseille, France & Département de Bio-Pathologie, Institut Paoli-Calmettes, Marseille, France
INSERM & Institut Paoli-Calmettes, Marseille, FranceDépartement d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille; INSERM UMR89; IFR137, Marseille, France & Département d'Oncologie médicale & Département de Biostatistiques, Institut Paoli-Calmettes, Marseille, France
INSERM, Marseille, FranceDépartement d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille; INSERM UMR89,; IFR137, Marseille, France
Institut Paoli-Calmettes, Marseille, FranceDépartement de Biostatistiques
INSERM & Institut Paoli-Calmettes & Université de la Méditerranée, Marseille, FranceDépartement d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille; INSERM UMR89,; IFR137, Marseille, France & Département de Bio-Pathologie & UFR de Médecine
UFR de Médecine, Université de la Méditerranée, Marseille, FranceINSERM UMR891, IFR137, Marseille, France
UFR de Médecine, Université de la Méditerranée, Marseille, France & IBiSA Cancer Immunomonitoring Platform, Centre de Recherche en Cancérologie de Marseille, Marseille, FranceUFR de Médecine & INSERM UMR891, IFR137, Marseille, France
Institut Paoli-Calmettes, Marseille, France & Université de la MéditerranéeDépartement de Bio-Pathologie & UFR de Médecine
Jacquemier, J., Bertucci, F., Finetti, P., Esterni, B., Charafe-Jauffret, E., Thibult, M.-L., Houvenaeghel, G., Van den Eynde, B., Birnbaum, D., Olive, D., & Xerri, L. (2012). High expression of indoleamine 2,3-dioxygenase in the tumour is associated with medullary features and favourable outcome in basal-like breast carcinoma. International Journal of Cancer, 130(1), 96-104. https://doi.org/10.1002/ijc.25979 (Original work published 2012)