Immunophenotypic and Genomic Characterisation of Papillary Carcinomas of the Breast
Raphaelle Duprez, Paul Wilkerson, Magali Lacroix-Triki, Maryou B Lambros, Alan Mackay, Roger A'Hern, Arnaud Gauthier, Pierre-Emmanuel Colombo, Frances Daley, Rachael Natrajan, Eric Ward, Gaetan MacGrogan, Flavie Arbion, Patrick Michenet, Britta Weigelt, Anne Vincent-Salomon, Jorge S Reis-Filho. The Institute of Cancer Research, London, United Kingdom; Institut Claudius Regaud, Toulouse, France; Institut Curie, Paris, France; Institut Bergonié, Bordeaux, France; Centre Hospitalier Universitaire, Tours, France; Centre Hospitalier Régional, Orléans, France; Cancer Research UK London Research Institute, London, United Kingdom
Background: Papillary carcinomas (PCs) are a rare histological special subtype of breast cancer associated with a favourable outcome. The aims of this study were to characterise the immunohistochemical characteristics, gene copy number aberrations and mutational repertoire of PCs, and to determine whether they would constitute an entity distinct from histological grade- and oestrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs).
Design: Sixty-three formalin-fixed paraffin-embedded PCs (39 encapsulated, nine solid, 12 invasive and three mixed encapsulated/ solid PCs) and 63 grade- and ER-matched IDC-NSTs were subjected to immunohistochemical profiling using a panel of 18 antibodies. DNA of sufficient quality was extracted from 49 microdissected PCs and 49 microdissected grade- and ER-matched IDC-NSTs, and subjected to high-resolution microarray-based comparative genomic hybridisation (aCGH) and MassARRAY Sequenom sequencing analysis of 19 known oncogenes.
Results: PCs were predominantly of low histological grade, expressed immunohistochemical markers consistent with a luminal phenotype, and displayed a lower rate of lymph node metastasis and p53 expression than grade- and ER-matched IDC-NSTs. PCs displayed less genomic aberrations than grade- and ER-matched IDC-NSTs; however the patterns of gene copy number aberrations found in PCs were similar to those of ER- and grade-matched IDC-NSTs, including 16q losses. Furthermore, PIK3CA mutations were found in 43% and 29% of PCs and grade- and ER-matched IDC-NSTs, respectively. The genomic profiles and mutational repertoires of encapsulated, solid and invasive PCs were remarkably similar.
Conclusions: Our results demonstrate that PCs are a homogeneous histological special type of breast cancer. The similarities of the genomic profiles of papillary carcinomas and grade- and ER-matched IDC-NSTs suggest that PCs may be best positioned as part of the spectrum of ER-positive breast cancers rather than as a distinct entity. Furthermore, the good prognosis of PCs may stem from the low rates of lymph node metastasis and p53 expression, low number of gene copy number aberrations, and high prevalence of PIK3CA mutations.
Monday, March 19, 2012 1:00 PM
Poster Session II # 73, Monday Afternoon