HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas.

1997 ◽  
Vol 15 (8) ◽  
pp. 2894-2904 ◽  
Author(s):  
M F Press ◽  
L Bernstein ◽  
P A Thomas ◽  
L F Meisner ◽  
J Y Zhou ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Gene Amplification ◽  
Poor Prognosis ◽  
Southern Hybridization ◽  
Recurrent Disease ◽  
Breast Cancers ◽  
Node Negative ◽  
Her 2

PURPOSE The HER-2/neu gene codes for a membrane receptor protein that is homologous, but distinct from the epidermal growth factor receptor. This investigation was performed to validate fluorescence in situ hybridization (FISH) as a sensitive and specific method for assessing HER-2/neu gene amplification in archival tissue and to test whether this alteration is associated with poor prognosis. MATERIALS AND METHODS HER-2/neu gene amplification was determined by FISH in 140 archival breast cancers, previously characterized for gene amplification by Southern hybridization or dot-blot hybridization, and for gene expression by Northern hybridization, Western immunoblot, or immunohistochemistry. A separate cohort of 324 node-negative breast cancers was assessed for amplification by FISH to determine the utility of HER-2/neu gene amplification. RESULTS Relative to solid-matrix blotting procedures, FISH analysis of HER-2/neu gene amplification showed a sensitivity of 98% and a specificity of 100% in 140 breast cancers. Among patients treated by surgery only, the relative risks (relative hazard) of early recurrence (recurrent disease within 24 months of diagnosis), recurrent disease (at any time), and disease-related death were statistically significantly associated with amplification. The prognostic information contributed by HER-2/neu amplification was independent of the other markers studied. CONCLUSION FISH was an alternative technique for determining gene amplification and had some distinct advantages over Southern hybridization. Our results demonstrate that HER-2/neu gene amplification in the absence of adjuvant therapy is an independent predictor of poor clinical outcome and is a stronger discriminant than tumor size. Women with small tumors that had gene amplification were at increased risk of recurrence and disease-related death.

HER-2/neu Analysis in Archival Tissue Samples of Human Breast Cancer: Comparison of Immunohistochemistry and Fluorescence In Situ Hybridization

2001 ◽  
Vol 19 (2) ◽  
pp. 354-363 ◽  
Author(s):  
Annette Lebeau ◽  
Daniela Deimling ◽  
Christine Kaltz ◽  
Andrea Sendelhofert ◽  
Anette Iff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Gene Amplification ◽  
Cancer Tissue ◽  
Breast Cancers ◽  
Paraffin Sections ◽  
Tissue Samples ◽  
Her 2

PURPOSE: The objective of our study was to compare the methods used in the literature to analyze HER-2/neu status on archival breast cancer tissue. Therefore, a series of antibodies was evaluated to assess their immunohistochemical (IHC) sensitivity in correlation to gene amplification determined by fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: HER-2/neu overexpression was studied on paraffin sections of 85 invasive breast cancers using a panel of five monoclonal (9G6, 3B5, CB11, TAB250, GSF-HER2) and two polyclonal antibodies (A8010, A0485) in addition to the HercepTest (DAKO, Glostrup, Denmark). HER-2/neu gene amplification was determined by FISH using a dual-color probe (PathVysion; Vysis, Stuttgart-Fasanenhof, Germany). RESULTS: HER-2/neu overexpression was demonstrated in 26% (9G6, TAB250, GSF-HER2), 27% (3B5, CB11), 33% (A8010) and 42% (A0485, HercepTest) of the tumors. FISH on paraffin sections identified gene amplification in 28% of the tumors. Strongly positive IHC results (3+) were always associated with gene amplification. Among the 16 tumors presented with weakly positive IHC results (2+) using the HercepTest, 12 (75%) lacked gene amplification. CONCLUSION: The comparison of IHC and FISH demonstrated an excellent correlation of high-level HER-2/neu overexpression (3+) with gene amplification; ie, FISH does not provide further information in these tumors. However, weakly positive IHC results (2+) obtained with the HercepTest share only a minor association with gene amplification.

Fluorescence In Situ Hybridization and Immunohistochemical Assays for HER-2/neu Status Determination

2001 ◽  
Vol 125 (6) ◽  
pp. 746-750
Author(s):  
Peter Onody ◽  
Françoise Bertrand ◽  
Françoise Muzeau ◽  
Ivan Bièche ◽  
Rosette Lidereau
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Lymph Node ◽  
Fluorescence In Situ Hybridization ◽  
Gene Amplification ◽  
Management Decision ◽  
Node Negative ◽  
Her 2 ◽  
Gene Alterations

Abstract Background.—HER-2/neu (ERBB2) gene amplification and/or overexpression is a major event in human breast tumorigenesis. HER-2/neu gene alterations have been the most frequently assessed prognostic factors during the last 10 years in breast cancer and have recently emerged as a management decision tool and a therapeutic target. There is still controversy over the best method to determine whether a tumor is HER-2/neu positive. Because of the increasing demand for HER-2/neu gene status determination in clinical practice, we compared HER-2/neu gene alterations at the DNA level (gene amplification) and the protein level (overexpression) in a panel of patients with lymph node–negative breast cancer who had received local radiotherapy alone, with no adjuvant therapy. Methods.—We tested 100 excised lymph node–negative breast tumors, using fluorescence in situ hybridization (FISH) with a biotinylated HER-2/neu DNA probe and immunohistochemical assays (IHC) with 2 different antibodies. Results.—The FISH frequency of HER-2/neu gene amplification was 15%, and the IHC frequency of overexpression was 21%. Conclusion.—Although HER-2/neu amplification by FISH and HER-2/neu overexpression by IHC correlated well in this panel of lymph node–negative breast carcinomas, there were a number of discordant cases, pointing to the important need for determining HER-2/neu alteration for the future management of HER-2/neu–based clinical applications.

scholarly journals Distinctive patterns of Her-2/neu, c-myc, and cyclin D1 gene amplification by fluorescence in situ hybridization in primary human breast cancers

Cytometry ◽  
2001 ◽  
Vol 46 (3) ◽  
pp. 136-149 ◽  
Author(s):  
Laura E. Janocko ◽  
Kathryn A. Brown ◽  
Charles A. Smith ◽  
Ling Ping Gu ◽  
Agnese A. Pollice ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Cyclin D1 ◽  
Gene Amplification ◽  
Breast Cancers ◽  
Human Breast ◽  
Her 2 ◽  
Primary Human Breast

A PILOT STUDY OF HER-2/NEU GENE AMPLIFICATION ASSESSED BY FLUORESCENCE IN SITU HYBRIDIZATION (FISH) IN GASTRIC CANCER

2014 ◽  
pp. 15-20
Author(s):  
Van Huy Tran ◽  
Thi Minh Thi Ha ◽  
Trung Nghia Van ◽  
Viet Nhan Nguyen ◽  
Phan Tuong Quynh Le ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Cancer Patients ◽  
Gene Amplification ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Her 2 ◽  
Gastric Cancer Patients

Background: HER-2/neu is a predictive biomarker for treatment of gastric cancer using trastuzumab in combination with chemotherapy. This study aimed to evaluate the status of HER-2/neu gene amplification using fluorescence in situ hybridization (FISH) in gastric cancer. Patients and methods: thirty six gastric cancer patients were assessed HER-2/neu gene amplification by FISH using PathVysionTM HER-2 DNA Probe kit (including HER-2/neu probe and CEP-17 probe) with biopsy and surgical specimens. Results: The HER-2/neu gene amplification was observed in three cases (8.3%), the HER-2/neu gene amplification rate in Lauren’s intestinal-type and diffuse-type were 11.8% and 5.2%, respectively. Conclusion: We applied successfully FISH technique with gastric cancer tissue samples. This technique could be performed as routine test in gastric cancer in order to select patients that benefit from trastuzumab in combination with chemotherapy.

scholarly journals Lower HER-2/chromosome enumeration probe 17 ratio in cytologic HER-2 fluorescence in situ hybridization for breast cancers

Cancer ◽  
2008 ◽  
Vol 114 (2) ◽  
pp. 134-140 ◽  
Author(s):  
Hitoshi Itoh ◽  
Yoko Miyajima ◽  
Shinobu Umemura ◽  
Robert Y. Osamura
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Breast Cancers ◽  
Her 2

Assessment of Methods for Tissue-Based Detection of the HER-2/neu Alteration in Human Breast Cancer: A Direct Comparison of Fluorescence In Situ Hybridization and Immunohistochemistry

2000 ◽  
Vol 18 (21) ◽  
pp. 3651-3664 ◽  
Author(s):  
Giovanni Pauletti ◽  
Suganda Dandekar ◽  
HongMei Rong ◽  
Lilllian Ramos ◽  
HongJun Peng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Gene Amplification ◽  
Survival Probability ◽  
Human Breast Cancer ◽  
Patient Survival ◽  
Human Breast ◽  
Her 2

PURPOSE: To compare the efficacy of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in detecting the HER-2/neu alteration in human breast cancer. PATIENTS AND METHODS: Unselected stage I, II, and III breast cancer patients (N = 900) were tested for HER-2/neu gene amplification by FISH in paraffin-embedded, formalin-fixed archival material. Of these samples, 856 were tested for HER-2/neu overexpression by non–antigen-retrieval IHC with the polyclonal antibody R60, the sensitivity and specificity of which was preliminarily compared with the United States Food and Drug Administration–approved HercepTest (Dako Corp, Carpinteria, CA). Patient survival was analyzed in relation to the presence of the HER-2/neu alteration as determined by these two methodologies. RESULTS: A total of 189 (21%) of 900 patients were positive by FISH and 147 (17.2%) of 856 were positive by IHC. This discrepancy is consistent with expected loss of IHC sensitivity associated with tissue fixation/embedding. The HercepTest did not improve sensitivity and introduced false positives. Comparison of R60-based IHC with FISH demonstrates that patient survival is associated progressively to gene amplification level as determined by FISH, whereas for IHC an association is found only in the highest (3+) immunostaining group. Among FISH-negative tumors, 45 (6.6%) of 678 were IHC-positive, with a survival probability similar to that of FISH-negative/IHC-negative cases; FISH-positive/IHC-negative patients have a survival probability similar to that of FISH-positive/IHC-positive cases. CONCLUSION: IHC does not consistently discriminate patients likely to have a poor prognosis, whereas FISH provides superior prognostic information in segregating high-risk from lower-risk beast cancers. HER-2/neu protein overexpression in the absence of gene amplification occurs infrequently in breast cancer, in which case, patient outcome is similar to that of patients without the alteration.

AMPLIFICATION AND OVEREXPRESSION OF HER2/NEU IN GASTRIC CANCER ASSESSED BY FLUORESCENCE IN SITU HYBRIDIZATION AND IMMUNOHISTOCHEMISTRY

2015 ◽  
pp. 22-31
Author(s):  
Van Huy Tran ◽  
Thi Minh Thi Ha ◽  
Viet Nho Le ◽  
Cong Thuan Dang ◽  
Trung Nghia Van ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Cancer Patients ◽  
Gene Amplification ◽  
Clinicopathologic Characteristics ◽  
Significant Difference ◽  
Her 2 ◽  
Gastric Cancer Patients

Background: HER2/neu is a predictive biomarker for treatment of gastric cancer using trastuzumab in combination with chemotherapy. This study aimed to: (1) assess the amplification and the overexpression of HER2/neu using fluorescence in situ hybridization (FISH) and immunohistochemistry in gastric cancer; (2) survey the association between HER2/neu and clinicopathologic characteristics of gastric cancer. Patients and methods: one hundred and sixty gastric cancer patients were assessed HER2/neu overexpression by IHC using Ventana anti-HER-2/neu (4B5) kit and were assessed HER2/neu gene amplification by FISH using PathVysionTM HER-2 DNA Probe kit with biopsy specimens. Results: HER2/neu protein expression rates of IHC 0, 1+, 2+ and 3+ were 70%, 10.6%, 10.6% and 8.8%, respectively. HER2/neu gene amplification was identified in gastric cancer from 21 out of 160 (13.1%) patients. The concordance between IHC and FISH was 90.0%. The HER2/neu-positive rate assessed by both techniques was 13.1%. There was a significant difference in HER2/neu-positivity between cardia gastric cancer and non-cardia gastric cancer (36.4% vs 11.4%, p = 0.040); between intestinal type and diffuse type (20.7% vs 5.9%, p = 0.010); between well, moderately differentiated and poorly differentiated gastric cancer (18.6% and 23.8% vs 5.8%, p = 0.047). Conclusion: We applied successfully FISH and IHC technique with biopsy samples in gastric cancer detecting HER2/neu positivity in order to select patients that benefit from trastuzumab in combination with chemotherapy. HER2/neu status associated with tumor location, Lauren classification and differentiated grading. Keywords: gastric cancer, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), HER-2/neu

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