Neuroendocrine Differentiation, Microsatellite Instability, and Tumor-infiltrating Lymphocytes in Advanced Colorectal Cancer With BRAF Mutation

Autor: Nora Sahnane, Carlo Capella, Fausto Sessa, Giovanni Veronesi, Nunzio Digiacomo, Graziella Pinotti, Marco Bregni, Filippo Crivelli, Claudio Verusio, Daniela Furlan, Elena Bolzacchini, Salvatore Artale, Roberta Cerutti
Rok vydání: 2019
Předmět:
Male
Colorectal cancer
Biopsy
Kaplan-Meier Estimate
CD8-Positive T-Lymphocytes
Neuroendocrine differentiation
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Medicine
CDX2
Colectomy
Proctectomy
biology
Gastroenterology
Cell Differentiation
Middle Aged
Prognosis
Advanced colorectal cancer
BRAF mutation
CD8 T-cell content
MSI
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
Female
Microsatellite Instability
030211 gastroenterology & hepatology
Colorectal Neoplasms
Proto-Oncogene Proteins B-raf
Colon
CD3
03 medical and health sciences
Lymphocytes
Tumor-Infiltrating
Neuroendocrine Cells
Stroma
Humans
neoplasms
Aged
business.industry
Tumor-infiltrating lymphocytes
Rectum
Microsatellite instability
medicine.disease
Survival Analysis
digestive system diseases
Mutation
Cancer research
biology.protein
Synaptophysin
business
Follow-Up Studies
Zdroj: Clinical Colorectal Cancer. 18:e251-e260
ISSN: 1533-0028
DOI: 10.1016/j.clcc.2018.12.003
Popis: Approximately 10% of metastatic colorectal cancer (mCRC) cases will harbor the BRAF p.V600E mutation (BRAF-mCRC) and have been associated with a poor prognosis. Although they are usually considered a unique clinical entity, biologic heterogeneity has been described. We performed an extensive clinicopathologic study of a multicenter series of BRAF-mCRC to highlight differences between tumors with microsatellite instability (MSI) and microsatellite stable tumors, focusing on both inflammatory profiles and neuroendocrine differentiation.We included 59 BRAF-mCRC cases and collected the clinical data (ie, surgery, treatment, and follow-up). We evaluated MSI status, budding, lympho-angioinvasion, neuroinvasion, extent of active stroma, CD3The 22 MSI BRAF-mCRC cases were associated with the right side (P .0001), an expansive grown pattern (P .01), programmed cell death ligand 1 expression (P .0001), high CD8 T-cell content (P = .0001), and lymph node metastases (P .029). The 37 MSS BRAF-mCRC cases were characterized by a greater stromal component (P = .0002), pulmonary metastases (P = .095), and p53 and synaptophysin immunoreactivity (P = .004 and P = .001, respectively). Univariate analysis demonstrated that MSI and a high CD8 T-cell content were associated with a 34% (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.34-1.28; P = .2) and 33% (HR, 0.67; 95% CI, 0.45-0.99; P = .04) reduction in the risk of death, respectively. The combined presence of MSI and CD8 T-cell content decreased the hazard of mortality ≤ 63% (HR, 0.37; 95% CI, 0.14-0.97; P = .2), which was slightly reduced after multivariate analysis.A simultaneous evaluation of MSI, CD8 T-cell content, and neuroendocrine markers could allow for the identification of subsets of BRAF-mCRC with a different prognosis and potential eligibility for specific treatments.
Databáze: OpenAIRE
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