Mixed micropapillary-ductal carcinomas of the breast: A genomic and immunohistochemical analysis of morphologically distinct components

Caterina Marchiò, Marjan Iravani, Rachael Natrajan, Maryou B K Lambros, Felipe C. Geyer, Kay Savage, Suzanne Parry, Narinder Tamber, Kerry Fenwick, Alan Mackay, Fernando C. Schmitt, Gianni Bussolati, Ian Ellis, Alan Ashworth, Anna Sapino, Jorge S. Reis-Filho

Research output: Contribution to journalArticlepeer-review

Abstract

Micropapillary carcinomas (MPCs) can present as a rare histological special type of breast cancer; however, this histological type is more frequently found admixed with invasive ductal carcinomas of no special type (IDC-NSTs). We have previously demonstrated that pure MPCs constitute a distinct entity at the morphological and genetic levels. Here, we sought to determine whether mixed MPCs have genomic aberrations similar to those found in pure MPCs, and to investigate whether the distinct morphological components of MPCs harbour different genetic aberrations. Using high-resolution microarray comparative genomic hybridization (aCGH), we profiled a series of 10 MPCs of mixed histology and 20 IDC-NSTs matched for grade and oestrogen receptor (ER) status. In addition, we generated tissue microarrays containing a series of 24 pure and 40 mixed MPCs and performed immunohistochemical analysis with ER, progesterone receptor (PR), Ki-67, HER2, cytokeratin (CK) 5/6, CK14, CK17, EGFR, topoisomerase-II?, cyclin D1, caveolin-1 and E-cadherin antibodies. In situ hybridization was employed to evaluate the prevalence of HER2, TOP2A, EGFR, CCND1, MYC and FGFR1 gene amplification. Our results demonstrate that mixed MPCs harbour similar patterns of genomic aberrations and phenotype (82.5% luminal and 17.5% HER2) compared to pure MPCs. A comparison between the distinct morphological components of mixed MPCs in a pairwise fashion revealed that both components harbour strikingly similar genomic profiles. When compared to grade- and ER-matched IDC-NSTs, mixed MPCs significantly more frequently harboured amplification of multiple regions on 8q (adjusted Fisher's p value

Original languageEnglish
Pages (from-to)301-315
Number of pages15
JournalJournal of Pathology
Volume218
Issue number3
DOIs
Publication statusPublished - Jul 2009

Keywords

  • Breast cancer
  • Chromogenic in situ hybridization
  • Comparative genomic hybridization
  • Histological type
  • Microarray

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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