Stromal signatures in endometrioid endometrial carcinomas

Iñigo Espinosa, Lluis Catasus, Emanuela Dangelo, Ana Mozos, Nuria Pedrola, Cristina Bértolo, Irene Ferrer, Gian Franco Zannoni, Robert B. West, Matt Van De Rijn, Xavier Matias-Guiu, Jaime Prat

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

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 (P<0.05). 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. © 2014 USCAP, Inc.
Original languageEnglish
Pages (from-to)631-639
JournalModern Pathology
Volume27
Issue number4
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • CSF1
  • endometrioid carcinoma
  • fibroblastic stromal response
  • macrophage stromal response
  • myometrial invasion
  • PIK3CA
  • tumor-associated macrophages

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