EP637 Are any pathologic variables of lymph node metastases reliable enough to predict survival in high grade endometrial cancer?

Wnt/β-catenin signaling pathway plays an established role in various diseases and is considered a hallmark of endometrial cancer (EC). Special AT-rich sequence-binding protein 1 and 2 (SATB1 and SATB2) are nuclear matrix-associated proteins involved in chromatin remodeling and regulation of gene expression. SATB1 promotes the progression of numerous types of cancers, whereas SATB2 acts as a tumor suppressor. Despite a recent progress in our knowledge about EC, the exact mechanisms that control their proliferation and metastatic potential still remain unknown. The aim of our study was to investigate the association between Wnt3A, β-catenin, SATB1 and SATB2 protein level and the clinicopathological features of EC patients. 92 EC patients, aged 37-84, were enrolled to our study. The immunoexpression of WNT3A was found in specimens from all EC patients, β-catenin was expressed in 97% of the cases, SATB1 in 87%. The significant association between Wnt3a expression and tumor grade was found; moreover mean IRS for Wnt3a turned out to be significantly lower in high-grade tumors than in low-grade malignancies (p=0.038). In turn, immunoexpression of β-catenin varied significantly across FIGO stages and was associated with the presence of lymph node metastases. Mean IRS for β-catenin in patients with lymph node metastases was significantly lower than in those without (p = 0.028). The Kaplan-Meier analyses demonstrated a stepwise impairment of cancer overall survival with increasing SATB1 expression. In conclusion, both Wnt/β-catenin signaling pathway and SATB1 contribute to progression of EC. Downregulation of β-catenin may predispose to lymphatic spread of EC. In turn, downregulation of Wnt3a seems to be characteristic for high-grade tumors, but probably does not play a role in formation of lymph node metastases. The important role of SATB1 as a predictor of poor survival and could be helpful in establishing a more accurate prognosis in endometrial cancer patients.

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Tumour-Infiltrating Lymphocytes (TILs) and PD-L1 Expression Correlate with Lymph Node Metastasis, High-Grade Transformation and Shorter Metastasis-Free Survival in Patients with Acinic Cell Carcinoma (AciCC) of the Salivary Glands

Cancers ◽

10.3390/cancers13050965 ◽

2021 ◽

Vol 13 (5) ◽

pp. 965

Author(s):

Selina Hiss ◽

Markus Eckstein ◽

Patricia Segschneider ◽

Konstantinos Mantsopoulos ◽

Heinrich Iro ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Lymph Node Metastases ◽

Immune Cell ◽

High Grade ◽

Free Survival ◽

Node Metastasis ◽

Node Metastases ◽

High Grade Transformation ◽

Infiltrating Lymphocytes

Objectives: The aim of this study was to assess the number of tumour-infiltrating lymphocytes (TILs) and the expression of Programmed Cell Death 1 Ligand 1 (PD-L1) in Acinic Cell Carcinoma (AciCC) of the salivary glands, to enable a correlation with clinico-pathological features and to analyse their prognostic impact. Methods: This single centre retrospective study represents a cohort of 36 primary AciCCs with long-term clinical follow-up. Immunohistochemically defined immune cell subtypes, i.e., those expressing T-cell markers (CD3, CD4 and CD8) or a B-cell marker (CD20) were characterized on tumour tissue sections. The number of TILs was quantitatively evaluated using software for digital bioimage analysis (QuPath). PD-L1 expression on the tumour cells and on immune cells was assessed immunohistochemically employing established scoring criteria: tumour proportion score (TPS), Ventana immune cell score (IC-Score) and combined positive score (CPS). Results: Higher numbers of tumour-infiltrating T- and B- lymphocytes were significantly associated with high-grade transformation. Furthermore, higher counts of T-lymphocytes correlated with node-positive disease. There was a significant correlation between higher levels of PD-L1 expression and lymph node metastases as well as the occurrence of high-grade transformation. Moreover, PD-L1 CPS was associated with poor prognosis regarding metastasis-free survival (p = 0.049). Conclusions: The current study is the first to demonstrate an association between PD-L1 expression and lymph node metastases as well as grading in AciCCs. In conclusion, increased immune cell infiltration of T and B cells as well as higher levels of PD-L1 expression in AciCC in association with high-grade transformation, lymph node metastasis and unfavourable prognosis suggests a relevant interaction between tumour cells and immune cell infiltrates in a subset of AciCCs, and might represent a rationale for immune checkpoint inhibition.

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