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Master Thesis

Caractérisation clinico-pathologique et moléculaire des carcinomes mammaires à cellules géantes osteoclast-like du stroma

Abstract : Breast carcinomas with osteoclast-like giant cells (COGC) are very rare. They show distinct stromal features, but their molecular characteristics remain insufficiently known. We report clinical and pathology data for 16 CCGO, and whole exome sequencing (WES) (8 COGC tumor/normal pairs) and RNA-seq results (7 COGC and 7 matched non-COCG Ca) for a subset of cases.Histology subtypes of COGC were: 11 (69%) non-specific type Ca(NST), four (25%) metaplastic Ca(MC) and one mixed NST/lobular Cawith focal COGC. Median age at diagnosis (years) was 46 (33-68) for COGC-NST and 72.5 (53-84) forCOGC-MC. Median tumor size was 18mm (6-32) for COCG-NST and 30mm (21-35) for COCG-MC. Elston-Ellis grade was 1 (n=4), 2 (n=6) or 3 (n=1) for COCG-NST and 3 for all COCG-MC. All COGC-NST were ER+, PR+, HER2-, Ki67 was <14% in 5 (45%) cases. All COGC-MC were triple-negative with Ki67>20%. Two COGC-NST and the mixed case had axillary lymph nodemetastases. AllCOGC-TNS patients were alive disease-free atmedian follow-up of 71 months(21-128) for COCG-TNS andone COCG-MC patient had inoperable recurrence, median follow-up 27 months (10-74). The patient with mixed Cadied of disease (metastases were non-COGC). There was evidence of recent or past stromal hemorrhage in all COGC casesand only one control. CD68+ infiltrate and CD34+ vessels were significantly more abundant in COGC than in controls, while CD163+ infiltrate and tumor-infiltrating lymphocytes were not. WES revealed mutations inPIK3CA(n=2), MAP3K1(n=1), MAP2K4(n=1), AKT1(n=1) and BRAF(n=1), but notTP53. Most cases (n=6)had simplex genomic profiles; 11p gain/16q loss (n=2), 8p loss (n=1), 16q loss (n=2) were seen. Transcriptomic profiles of COGC differed strikingly from controls. Upregulated pathwaysincluded osteoclast maturation and function. There was significant upregulation ofRANK,RANKLand downregulation ofOPG.
Conclusion: most COCG are luminal A or B IC-NST in young patients,and a subset are MC. Their genomics are somewhat similar to non-COCG luminal IC-NST except for absence ofTP53mutations, but gene expression profiles are strikingly different. Exploring the RANK/RANKL/OPG axis appears warranted.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03142504
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Submitted on : Wednesday, June 30, 2021 - 3:47:41 PM
Last modification on : Saturday, November 13, 2021 - 3:53:42 AM

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Joanna Cyrta. Caractérisation clinico-pathologique et moléculaire des carcinomes mammaires à cellules géantes osteoclast-like du stroma. Médecine humaine et pathologie. 2019. ⟨dumas-03142504⟩

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