HER-2/neu amplification by fluorescence in situ hybridization in cytologic samples from distant metastatic sites of breast carcinoma.
BACKGROUND
Amplification of the HER-2/neu oncogene has been proposed as a target for antibody-based therapies and as a predictor of chemoresponsiveness in advanced breast carcinoma. Few studies have concentrated on HER-2/neu gene evaluation by fluorescence in situ hybridization (FISH) on distant metastatic sites and none have been performed on cytologic samples. The current study evaluated HER-2/neu amplification by FISH on cytologic samples obtained from distant metastatic lesions of breast carcinoma to update HER-2/neu characterization through a safe and easier procedure than biopsy.


METHODS
Twenty-two cytologic samples from distant metastases (12 hepatic samples, 4 skin samples, 3 pleural samples, and 3 peritoneal samples) were submitted to HER-2/neu evaluation by FISH. Seventeen corresponding primary breast tumors also were evaluated by FISH on paraffin histologic sections or on destained archival cytologic smears.


RESULTS
Seven of the 22 metastases (32%) were amplified. Amplification was observed in 4 of the 12 liver metastases, in 1of the 3 ascitic fluid specimens, and in 2 of the 4 skin metastases. In all the three pleural fluid specimens, HER-2/neu was unamplified. Matched results from primary and metastatic lesions were obtained in 14 cases (5 were amplified and 9 were unamplified on both primary and metastatic tumors).


CONCLUSIONS
The results of the current study emphasized the feasibility and advantages of two rapid and very informative techniques, such as fine-needle aspiration biopsy and FISH. Both procedures were performed to ascertain the malignant nature of a suspicious lesion and to obtain predictive markers for response. Since the advent of trastuzumab, the characterization of the molecular profile in metastatic breast disease has become increasingly important for targeted therapy selection.
Department of Medical Oncology, University Hospital, Parma, Italy. cbozzetti@ao.pr.it
Cecilia
C
Bozzetti
Nicola
N
Personeni
Rita
R
Nizzoli
Annamaria
A
Guazzi
Marcella
M
Flora
Cristina
C
Bassano
Francesca
F
Negri
Eugenia
E
Martella
Nadia
N
Naldi
Vittorio
V
Franciosi
Stefano
S
Cascinu
D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics* / Q000556:secondary*; D046508:Culture Techniques; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000556:secondary; D010997:Pleural Neoplasms / Q000235:genetics / Q000556:secondary; D011379:Prognosis; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000235:genetics / Q000556:secondary