HER-2/neu amplification by fluorescence in situ hybridization in cytologic samples from distant metastatic sites of breast carcinoma.

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. 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. 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). 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.

Bozzetti C ，Personeni N ，Nizzoli R ，Guazzi A ，Flora M ，Bassano C ，Negri F ，Martella E ，Naldi N ，Franciosi V ，Cascinu S ... -  《CANCER》

Comparison of HER-2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma.

Accurate assessment of HER-2 status is necessary prior to anti-HER-2 antibody (trastuzumab) therapy for metastatic breast carcinoma. However, controversy exists regarding whether to assess HER-2 status in the primary tumor or in metastatic lesions. It is also unclear whether HER-2 status can change during disease progression or after chemotherapy. Breast carcinoma samples from 60 women with known HER-2 status in both primary tumors and paired metastases (locoregional disease, n = 43 patients; distant disease, n = 17 patients) were reviewed retrospectively. Thirty-two patients underwent chemotherapy before their metastatic lesions were sampled, including 18 patients who received neoadjuvant chemotherapy and 14 patients who received adjuvant chemotherapy. The HER-2 gene was examined by fluorescence in situ hybridization either in paraffin-embedded tissue samples (48 primary tumors and 9 metastatic tumors) or in fine-needle aspirates (12 primary tumors and 51 metastatic tumors). HER-2 gene amplification was defined as a HER-2:chromosome 17 signal ratio >/= 2.0. The HER-2 status of primary and metastatic tumors agreed in 58 of 60 patients (97%), including 18 (30%) amplified tumors and 40 (67%) nonamplified tumors. A discrepancy in HER-2 status was observed in specimens from two patients in which HER-2 amplification was detected in the primary tumor but not the metastatic tumors. In one patient, three foci of tumor nodules were found in the same breast; the HER-2 status was assessed in only one of them, which showed amplification; however, HER-2 amplification was not detected in the axillary lymph node metastasis. In another patient, the HER-2 gene was amplified in the primary tumor but not in the liver metastasis. No metastases showed HER-2 amplification without amplification in the primary tumor. Locoregional and distant metastases demonstrated similar concordance rates with their corresponding primary tumors (98% and 94%, respectively). Complete concordance of HER-2 status was found between primary tumors prior to chemotherapy and metastases that were sampled after chemotherapy. The HER-2 status in breast carcinoma generally was stable during metastasis, whether to locoregional or distant sites. Chemotherapy did not modify the HER-2 status in metastatic lesions. Therefore, HER-2 amplification can be evaluated reliably in material from either primary or metastatic tumors in most patients. Further study with larger series is warranted to elucidate the significance of discordant results.

Gong Y ，Booser DJ ，Sneige N 《CANCER》

Amplification of Her-2/neu gene in Her-2/neu-overexpressing and -nonexpressing breast carcinomas and their synchronous benign, premalignant, and metastatic lesions detected by FISH in archival material.

Xu R ，Perle MA ，Inghirami G ，Chan W ，Delgado Y ，Feiner H ... -  《MODERN PATHOLOGY》

HER-2/neu evaluation by fluorescence in situ hybridization on destained cytologic smears from primary and metastatic breast cancer.

Nizzoli R ，Guazzi A ，Naldi N ，Fraciosi V ，Bozzetti C ... -  《-》

Detection of low level HER-2/neu gene amplification in prostate cancer by fluorescence in situ hybridization.

Liu HL ，Gandour-Edwards R ，Lara PN Jr ，de Vere White R ，LaSalle JM ... -  《CANCER JOURNAL》