Myometrial Invasion and Lymph Node Metastasis in Endometrioid Carcinomas: Tumor-associated Macrophages, Microvessel Density, and HIF1A Have a Crucial Role

Espinosa, Íñigo; Carnicer, Maria J.; Catasús, Lluis; Canet, Belén; D’Angelo, Emanuela; Zannoni, Gian Franco; Prat, Jaime

doi:10.1097/pas.0b013e3181f32168

Cited by 67 publications

(58 citation statements)

References 21 publications

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“…However, we unexpectedly found that cases with lymph node metastasis had a lower mean value of CET1-w_5_fos_median than did cases without lymph node metastasis. Almost all previous studies have reported the contrary result that angiogenesis is positively correlated with lymph node metastasis (48)(49)(50). The reason for this discrepancy may be NPC patients often experienced lymph node metastasis even in the low-stage (stage I-II).…”

Section: Discussioncontrasting

confidence: 39%

Radiomics Features of Multiparametric MRI as Novel Prognostic Factors in Advanced Nasopharyngeal Carcinoma

Zhang

Tian

Dong

et al. 2017

Clinical Cancer Research

430

351

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Purpose: To identify MRI-based radiomics as prognostic factors in patients with advanced nasopharyngeal carcinoma (NPC).Experimental Design: One-hundred and eighteen patients (training cohort: n ¼ 88; validation cohort: n ¼ 30) with advanced NPC were enrolled. A total of 970 radiomics features were extracted from T2-weighted (T2-w) and contrast-enhanced T1-weighted (CET1-w) MRI. Least absolute shrinkage and selection operator (LASSO) regression was applied to select features for progression-free survival (PFS) nomograms. Nomogram discrimination and calibration were evaluated. Associations between radiomics features and clinical data were investigated using heatmaps.Results: The radiomics signatures were significantly associated with PFS. A radiomics signature derived from joint CET1-w and T2-w images showed better prognostic performance than signatures derived from CET1-w or T2-w images alone. One radiomics nomogram combined a radiomics signature from joint CET1-w and T2-w images with the TNM staging system. This nomogram showed a significant improvement over the TNM staging system in terms of evaluating PFS in the training cohort (C-index, 0.761 vs. 0.514; P < 2.68 Â 10 À9 ). Another radiomics nomogram integrated the radiomics signature with all clinical data, and thereby outperformed a nomogram based on clinical data alone (C-index, 0.776 vs. 0.649; P < 1.60 Â 10 À7 ). Calibration curves showed good agreement. Findings were confirmed in the validation cohort. Heatmaps revealed associations between radiomics features and tumor stages. Conclusions: Multiparametric MRI-based radiomics nomograms provided improved prognostic ability in advanced NPC. These results provide an illustrative example of precision medicine and may affect treatment strategies.

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Section: Discussioncontrasting

confidence: 39%

Radiomics Features of Multiparametric MRI as Novel Prognostic Factors in Advanced Nasopharyngeal Carcinoma

Zhang

Tian

Dong

et al. 2017

Clinical Cancer Research

430

351

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“…88 In contrast, certain other studies failed to demonstrate significant correlations between CD68 + TAM density and prognosis, 89 although they did find associations with myometrial invasion and microvessel density. 89 In a macrophage phenotype analysis, CD163 + M2-TAM density correlated significantly with myometrial invasion, microvessel density, and regional lymph node metastasis, 90 but a correlation with prognosis was not described.…”

Section: Endometrial Cancermentioning

confidence: 99%

Role of tumor‐associated macrophages in human malignancies: friend or foe?

Takeya

Komohara

2016

Pathology International

154

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Tumor-associated macrophages (TAMs) play a pivotal role in tumor growth in human malignancies. Published studies have analyzed the relationship between TAM infiltration and the prognosis of patients for many human tumors. Most studies reported a positive correlation between TAM density and a poor prognosis. Studies focusing on macrophage phenotypes emphasized the protumor role of M2 anti-inflammatory macrophages in many types of human tumors. However, TAMs influence tumor progression in various ways that depend on differences in tumor sites, histology, and microenvironments. In this review, we summarize the function of TAMs in various human malignancies by reviewing the data provided in studies of TAMs in human malignancies.

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“…30 In a previous study, we also encountered a positive correlation between CD163-macrophages in primary endometrioid endometrial carcinomas and their matched lymph node metastases. 31 In the current study, we found that the expression of CSF1 by the tumor cells of primary endometrioid endometrial carcinomas is maintained in most metastatic tumors. These findings suggest that the CSF1 macrophage response signature is determined by the intrinsic biology of the tumor and is independent of the microenvironment the tumor resides in.…”

Section: Discussionmentioning

confidence: 66%

Stromal signatures in endometrioid endometrial carcinomas

et al. 2014

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The pattern of myometrial invasion in endometrioid endometrial carcinomas varies considerably; ie, from widely scattered glands and cell nests, often associated with a fibromyxoid stromal reaction (desmoplasia) and/ or a lymphocytic infiltrate, to invasive glands with little or no stromal response. Recently, two distinct stromal signatures derived from a macrophage response (colony-stimulating factor 1, CSF1) and a fibroblastic response (desmoid-type fibromatosis, DTF) were identified in breast carcinomas and correlated with clinicopathologic features including outcome. In this study, we explored whether these stromal signatures also apply to endometrioid carcinomas and how their expression patterns correlated with morphologic changes. We studied the stromal signatures both by immunohistochemistry and in situ hybridization in 98 primary endometrioid carcinomas with (87 cases) and without (11 cases) myometrial invasion as well as in the corresponding regional lymph nodes metatases of 9 myoinvasive tumors. Desmoplasia correlated positively with the DTF expression signature. Likewise, mononuclear infiltrates were found in the stroma of tumors expressing CSF1. Twenty-four out of eighty-seven (27%) myoinvasive endometrioid carcinomas were positive for the macrophage signature and thirteen out of eighty-seven (15%) expressed the fibroblast signature. Eleven additional cases were positive for both DTF and CSF1 signatures (11/87; 13%). However, over half of the cases (39/87; 45%) and the majority of the non-myoinvasive tumors (8/11; 73%) failed to express any of the two stromal signatures. The macrophage response (CSF1) was associated with higher tumor grade, lymphovascular invasion, and PIK3CA mutations (Po0.05). There was a concordance in the expression of the CSF1 signature in the primary tumors and their corresponding lymph node metastases. This study is the first characterization of stromal signatures in endometrioid carcinomas. Our findings shed new light on the relationship between genetically different endometrioid carcinomas and various stromal responses. Preservation of the CSF1 macrophage stromal response in the metastases leds support to targeting the CSF1 pathway in endometrioid endometrial carcinomas.

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Myometrial Invasion and Lymph Node Metastasis in Endometrioid Carcinomas: Tumor-associated Macrophages, Microvessel Density, and HIF1A Have a Crucial Role

Cited by 67 publications

References 21 publications

Radiomics Features of Multiparametric MRI as Novel Prognostic Factors in Advanced Nasopharyngeal Carcinoma

Radiomics Features of Multiparametric MRI as Novel Prognostic Factors in Advanced Nasopharyngeal Carcinoma

Role of tumor‐associated macrophages in human malignancies: friend or foe?

Stromal signatures in endometrioid endometrial carcinomas

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