Monosomy of chromosome 17 in breast cancer during interpretation of HER2 gene amplification.
Monosomy of chromosome 17 may affect the assessment of HER2 amplification. Notably, the prevalence ranges from 1% up to 49% due to lack of consensus in recognition. We sought to investigate the impact of monosomy of chromosome 17 to interpretation of HER2 gene status. 201 breast carcinoma were reviewed for HER2 gene amplification and chromosome 17 status. FISH analysis was performed by using double probes (LSI/CEP). Absolute gene copy number was also scored per each probe. HER2 FISH test was repeated on serial tissue sections, ranging in thickness from 3 to 20 µm. Ratio was scored and subsequently corrected by monosomy after gold control test using the aCGH method to overcome false interpretation due to artefactual nuclear truncation. HER2 immunotests was performed on all cases. 26/201 cases were amplified (13%). Single signals per CEP17 were revealed in 7/201 (3.5%) cases. Five out of 7 cases appeared monosomic with aCGH (overall, 5/201, 2.5%) and evidenced single signals in >60% of nuclei after second-look on FISH when matching both techniques. Among 5, one case showed amplification with a pattern 7/1 (HER2/CEP17>2) of copies (3+ at immunotest); three cases revealed single signals per both probes (LSI/CEP=1) and one case revealed a 3:1 ratio; all last 4 cases showed 0/1+ immunoscore. We concluded that: 1) monosomy of chromosome 17 may be observed in 2.5% of breast carcinoma; 2) monosomy of chromosome 17 due to biological reasons rather than nuclear truncation was observed when using the cut-off of 60% of nuclei harboring single signals; 3) the skewing of the ratio due to single centromeric 17 probe may lead to false positive evaluation; 4) breast carcinomas showing a 3:1 ratio (HER2/CEP17) usually show negative 0/1+ immunoscore and <6 gene copy number at FISH.
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Matteo
M
Brunelli
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Alessia
A
Nottegar
Anatomic Pathology, Sacro Cuore Don Calabria Hospital Negrar, Italy.
Giuseppe
G
Bogina
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Anna
A
Caliò
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Luca
L
Cima
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Albino
A
Eccher
ARC-NET Applied Research Centre, University of Verona Italy.
Caterina
C
Vicentini
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Lisa
L
Marcolini
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy ; ARC-NET Applied Research Centre, University of Verona Italy.
Aldo
A
Scarpa
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Serena
S
Pedron
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Eleonora
E
Brunello
Department of Pathology, Laboratory of Molecular Cytogenetic, University of Helsinki Finland.
Sakari
S
Knuutila
Department of Medical Sciences, Anatomic Pathology, University and Hospital Trust Turin, Italy.
Anna
A
Sapino
Department of Medical Sciences, Anatomic Pathology, University and Hospital Trust Turin, Italy.
Caterina
C
Marchiò
Medical Oncology, University and Hospital Trust Verona, Italy.
Emilio
E
Bria
Medical Oncology, University and Hospital Trust Verona, Italy.
Annamaria
A
Molino
Medical Oncology, University and Hospital Trust Verona, Italy.
Luisa
L
Carbognin
Medical Oncology, University and Hospital Trust Verona, Italy.
Giampaolo
G
Tortora
Institute of Cancer & Genetics, Pathology, Cardiff University United Kingdom.
Bharat
B
Jasani
UK NEQAS, University College of London United Kingdom.
Keith
K
Miller
UK NEQAS, University College of London United Kingdom.
Ibrahim
I
Merdol
Anatomic Pathology, S. Maria di Ca' Foncello Hospital Treviso, Italy.
Lucia
L
Zanatta
Anatomic Pathology, S. Maria di Ca' Foncello Hospital Treviso, Italy.
Licia
L
Laurino
Department of Pathology, Laboratory of Molecular Cytogenetic, University of Helsinki Finland ; Department of Pathology, HUSLab, University Central Hospital Helsinki, Finland.
Tiina
T
Wirtanen
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy ; Anatomic Pathology, Sacro Cuore Don Calabria Hospital Negrar, Italy.
Giuseppe
G
Zamboni
Anatomic Pathology, Sacro Cuore Don Calabria Hospital Negrar, Italy.
Marcella
M
Marconi
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Marco
M
Chilosi
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Erminia
E
Manfrin
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Guido
G
Martignoni
Department of Pathology and Diagnostic, Anatomic Pathology, University and Hospital Trust Verona, Italy.
Franco
F
Bonetti
Breast carcinoma; FISH analysis; HER 2 amplification; aCGH method; chromosome 17; double probes; false positive; monosomy; ratio (HER2/CEP 17); single signals