RESUMO
INTRODUCTION: Mismatch repair deficiency, immunological fertility, and PD-L1 expression status are key histopathological and molecular features defining tumor responsiveness to immunotherapy and, eventually, prognosis. These were investigated in a series of locally advanced rectal cancer patients treated with postoperative chemotherapy and radiotherapy. MATERIALS AND METHODS: Tumor-infiltrating lymphocyte (TIL) density was assessed in hematoxylin-eosin tissue sections. PD-L1 expression and the expression of MMR proteins (MLH1, PSM2, MSH2, and MSH6) were assessed with immunohistochemistry. Their association with histopathological variables (node involvement and tumor budding) and prognosis was assessed. RESULTS: The TIL-density was significantly higher in the invading tumor front and was inversely related to tumor budding and directly with better overall survival (OS) and distant metastasis-free survival (DMFS) (p = 0.02 and 0.02, respectively). Cancer cell PD-L1 expression was related to high TIL-density (p < 0.01) but not to prognosis, although its overexpression defined a trend for poorer OS in patients with high TIL-density. High PD-L1 expression by stroma infiltrating immune cells was linked with better OS and DMFS (p = 0.007 and 0.001, respectively. MMR deficiency was recorded in 26.2 % of cases, and this was linked with higher TIL-density, but not with prognosis. CONCLUSIONS: Dense intratumoral lymphocytic infiltration relates to a better prognosis in rectal cancer, although it is also linked with PD-L1 expression that may adversely modulate the anti-tumor effects of TILs. This latter subgroup of patients (high TIL-density/high cancer cell PD-L1 expression) could be an additional target for anti-PD-1/PD-L1 immunotherapy, along with the established subgroup of MMR deficient patients.
Assuntos
Antígeno B7-H1 , Imunoterapia , Linfócitos do Interstício Tumoral , Neoplasias Retais , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Antígeno B7-H1/metabolismo , Feminino , Masculino , Neoplasias Retais/terapia , Neoplasias Retais/mortalidade , Neoplasias Retais/imunologia , Neoplasias Retais/patologia , Neoplasias Retais/genética , Imunoterapia/métodos , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Reparo de Erro de Pareamento de DNA , Biomarcadores Tumorais , Síndromes Neoplásicas Hereditárias/terapia , Síndromes Neoplásicas Hereditárias/genética , Microambiente Tumoral/imunologia , Imuno-Histoquímica , Neoplasias Encefálicas , Neoplasias ColorretaisRESUMO
AIM: To define the role of prophylactic parathyroidectomy in the surgical treatment of medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type IIa (MEN2A) syndrome through a literature review.