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男性乳腺癌——脂肪酸合酶(FASN)、活化转录因子3(ATF3)和Ⅳ型胶原的免疫组织化学模式及临床相关性

Male Breast Cancer-Immunohistochemical Patterns and Clinical Relevance of FASN, ATF3, and Collagen IV.

作者信息

André Saudade, Pinto António E, Silva Giovani L, Silva Fernanda, Serpa Jacinta, Félix Ana

机构信息

Department of Pathology, Portuguese Institute of Oncology of Lisbon, Lisbon, Portugal.

Department of Mathematics of Higher Technical Institute (Instituto Superior Técnico), Faculty of Sciences (Faculdade de Ciências), University of Lisbon, Lisbon, Portugal.

出版信息

Breast Cancer (Auckl). 2021 Apr 8;15:11782234211002496. doi: 10.1177/11782234211002496. eCollection 2021.

Abstract

BACKGROUND

Male breast carcinoma (male BC) is an uncommon neoplasia without individualized strategies for diagnosis and therapeutics. Low overall survival (OS) rates have been reported, mostly associated with patients' advanced stage and older age. Intratumoral heterogeneity versus homogeneity of malignant epithelial cells seems to be an important factor to consider for the development of combination therapies with curative intention.

OBJECTIVE

In this preliminary study, we aim to provide valuable insight into the distinct clinicopathologic features of male BC.

MATERIAL AND METHODS

In a series of 40 male BC patients, we evaluated by immunohistochemistry androgen receptor; activating transcription factor 3 (ATF3); p16; cyclin D1; fatty acid synthase (FASN); fatty acid transport protein 1 (FATP1); β1, β3, β4, and β6 integrins; collagen I and collagen IV; and their interactions. Kaplan-Meier survival curves and log-rank tests were assessed for statistical analysis.

RESULTS

Homogeneous epithelial staining of p16, ATF3, β6 integrin, FASN, and FATP1 was found to be significantly intercorrelated, and associated with high Ki67. These markers also stained tumor stromal fibroblasts. The prognostic analysis showed statistically significant associations of FASN with disease-free survival (DFS) and OS, as well as of ATF3 with OS and collagen IV with DFS.

CONCLUSIONS

This study highlights, as a novel finding, the relevance of FASN, ATF3, and collagen IV immunophenotypes, which may have innovative application in the clinical management of male BC.

摘要

背景

男性乳腺癌(male BC)是一种罕见的肿瘤,缺乏个体化的诊断和治疗策略。据报道,其总体生存率(OS)较低,这主要与患者的晚期阶段和高龄有关。恶性上皮细胞的肿瘤内异质性与同质性似乎是制定具有治愈意图的联合治疗方案时需要考虑的一个重要因素。

目的

在这项初步研究中,我们旨在深入了解男性乳腺癌独特的临床病理特征。

材料与方法

在40例男性乳腺癌患者中,我们通过免疫组织化学评估了雄激素受体;激活转录因子3(ATF3);p16;细胞周期蛋白D1;脂肪酸合酶(FASN);脂肪酸转运蛋白1(FATP1);β1、β3、β4和β6整合素;胶原蛋白I和胶原蛋白IV;以及它们之间的相互作用。采用Kaplan-Meier生存曲线和对数秩检验进行统计分析。

结果

发现p16、ATF3、β6整合素、FASN和FATP1的上皮细胞均匀染色显著相互关联,并与高Ki67相关。这些标志物也对肿瘤基质成纤维细胞进行染色。预后分析显示,FASN与无病生存期(DFS)和OS、ATF3与OS以及胶原蛋白IV与DFS之间存在统计学显著关联。

结论

本研究作为一项新发现,突出了FASN、ATF3和胶原蛋白IV免疫表型的相关性,它们可能在男性乳腺癌的临床管理中具有创新性应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2045/8040573/031d044d7cd1/10.1177_11782234211002496-fig1.jpg

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