Share This Article:

Detection of HER-2/neu Amplification on Fine Needle Aspirates of Breast Cancer Using Fluorescence in Situ Hybridization

Abstract Full-Text HTML Download Download as PDF (Size:432KB) PP. 41-48
DOI: 10.4236/jct.2013.47A007    4,251 Downloads   5,777 Views  

ABSTRACT

The accuracy of diagnostic assays for HER-2/neu in breast cancer is extremely important as HER-2/neu status is essential in tailoring adjuvant and/or neoadjuvant treatment in every patient. FNAC is widely practiced in Egypt in preoperative diagnosis of breast cancer for its low cost and high diagnostic accuracy. Since the determination of HER-2/neu protein expression on cytological preparations was previously found to be unreliable for clinical use, we opted for the assessment of HER-2/neu status in fine needle aspirates using FISH. The main objective of this study was to evaluate the reliability of HER-2/neu status assessment by FISH on fine needle aspirates of breast cancers by comparing the results with IHC and FISH on FFPE tissue sections obtained from corresponding surgically resected specimens. Fine needle aspirates from 40 breast cancer patients with pathologically confirmed breast cancer were included in the study. They were submitted for HER-2/neu evaluation by FISH. After surgery, the corresponding FFPE sections were evaluated for HER-2/neu by FISH and by IHC. FNAs from 11 cases proved to be amplified by FISH, while 29 cases were not amplified. Apart from two cases that showed lack of signals, all specimens evaluated by FISH on the corresponding FFPE sections showed matched results. The Measurement of Agreement between FISH on FNAs and FISH on FFPE sections was 86.7%, while that between FISH on FNAs and IHC was 72.5%. The high concordance rate in the present study between FISH evaluation of HER-2/neu gene amplification on FNAC samples and their corresponding FFPE samples indicate that FISH may be a reliable technique for HER-2/neu assessment on FNAs. Furthermore, FISH on FNAs gave us better hybridization signals than their corresponding FFPE tissue sections. Finally, we also conclude that all score (2+) cases by IHC should be reevaluated by FISH which is crucial for the patient management.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

T. Iman, S. Amani and A. Mona, "Detection of HER-2/neu Amplification on Fine Needle Aspirates of Breast Cancer Using Fluorescence in Situ Hybridization," Journal of Cancer Therapy, Vol. 4 No. 7A, 2013, pp. 41-48. doi: 10.4236/jct.2013.47A007.

References

[1] Middle East Cancer Consortium (MECC) Egypt, “The Gharbiah Population-Based Cancer Registry,” Ministry of Health and Populations Egypt and Middle East Cancer Consortium, Cairo, 1999.
[2] National Cancer Institue, “Cairo University, Egypt. Cancer Registry 2002-2003,” National Cancer Institue, Cairo.
[3] J. Hannemann, P. Kristel, H. van Tinteren, M. Bontenbal, Q. G. van Hoesel, W. M. Smit, et al., “Molecular Subtypes of Breast Cancer and Amplification of Topoisomerase II Alpha: Predictive Role in Dose Intensive Adjuvant Chemotherapy,” British Journal of Cancer, Vol. 95, No. 10, 2006, pp. 1334-41.
[4] R. B. Dickson, R. G. Pestell and M. E. Lippman, “Cancer of the Breast,” In: V. Devita, S. Hellman and S. A. Rosenberg, Cancer Principles & Practice of Oncology, 7th Edition, Lippincott, Williams & Wilkins, Philadelphia, 2005, pp. 1595-1654.
[5] R. A. Walker, J. M. Bartlett, M. Dowsett, I. O. Ellis, A. M. Hanby, B. Jasani, et al., “HER2 Testing in the UK: Further Update to Recommendations,” Journal of Clinical Pathology, Vol. 61, No. 7, 2008, pp. 818-824. doi:10.1136/jcp.2007.054866
[6] D. Varshney, Y. Y. Zhou, S. A. Geller and R. Alsabeh, “Determination of HER-2 Status and Chromosome 17 Polysomy in Breast Carcinomas Comparing HercepTest and PathVysion FISH Assay,” American Journal of Clinical Pathology, Vol. 121, No. 1, 2004, pp. 70-77. doi:10.1309/FUQH92B039025LHG
[7] H. J. Burstein, L. N. Harris, R. Gelman, S. C. Lester, R. A. Nunes, C. M. Kaelin, et al., “Preoperative Therapy with Trastuzumab and Paclitaxel Followed by Sequential Adjuvant Doxorubicin/Cyclophosphamide for HER2 Overexpressing Stage II or III Breast Cancer: A Pilot Study,” Journal of Clinical Oncology, Vol. 21, No. 1, 2003, pp. 46-53.
[8] M. F. Press, R. S. Finn, D. Cameron, A. Di Leo, C. E. Geyer, I. E. Villalobos, et al., “HER-2 Gene Amplification, HER-2 and Epidermal Growth Factor Receptor mRNA and Protein Expression, and Lapatinib Efficacy in Women with Metastatic Breast Cancer,” Clinical Cancer Research, Vol. 14, No. 23, 2008, pp. 7861-7870.
[9] P. L. Fitzgibbons, D. A. Murphy, D. M. Dorfman, P. C. Roche and R. R. Tubbs, “Interlaboratory Comparison of Immunohistochemical Testing for HER2: Results of the 2004 and 2005 College of American Pathologists HER2 Immunohistochemistry Tissue Microarray Survey,” Archives of Pathology & Laboratory Medicine, Vol. 130, No. 10, 2006, pp. 1440-1445.
[10] A. Rhodes, B. Jasani, E. Anderson, A. R. Dodson and A. J. Balaton, “Evaluation of HER-2/neu Immunohistochemical Assay Sensitivity and Scoring on Formalin-Fixed and Paraffin-Processed Cell Lines and Breast Tumors: A Comparative Study Involving Results from Laboratories in 21 Countries,” American Journal of Clinical Pathology, Vol. 11, No. 3, 2002, pp. 408-417.
[11] M. B. Lambros, R. Natrajan and J. S. Reis-Filho, “Chromogenic and Fluorescent in Situ Hybridization in Breast Cancer,” Human Pathology, Vol. 38, No. 8, 2007, pp. 1105-1022. doi:10.1016/j.humpath.2007.04.011
[12] M. F. Press, G. Sauter, L. Bernstein, I. E. Villalobos, M. Mirlacher, J. Y. Zhou, et al., “Diagnostic Evaluation of HER-2 as a Molecular Target: An Assessment of Accuracy and Reproducibility of Laboratory Testing in Large, Prospective, Randomized Clinical Trials,” Clinical Cancer Research, Vol. 11, No. 18, 2005, pp. 6598-6607.
[13] H. Yaziji, L. C. Goldstein, T. S. Barry, R. Werling, H. Hwang, G. K. Ellis, et al., “HER-2 Testing in Breast Cancer Using Parallel Tissue-Based Methods,” JAMA Network, Vol. 291, No. 16, 2004, pp. 1972-1977.
[14] L. Arnould, P. Roger, G. Macgrogan, M. P. Chenard, A. Balaton, S. Beauclair, et al., “Accuracy of HER2 Status Determination on Breast Core-Needle Biopsies (Immunohistochemistry, FISH, CISH and SISH vs FISH),” Modern Pathology, Vol. 25, No. 5, 2012, pp. 675-682.
[15] A. C. Wolff, M. E. Hammond, J. N. Schwartz, K. L. Hagerty, D. C. Allred, R. J. Cote, et al., “American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer,” Journal of Clinical Oncology, Vol. 25, No. 1, 2007, pp. 118-145. doi:10.1200/JCO.2006.09.2775
[16] I. O. Ellis, J. Bartlett, M. Dowsett, S. Humphreys, B. Jasani, K. Miller, et al., “Best Practice No 176: Updated Recommendations for HER2 Testing in the UK,” Journal of Clinical Pathology, Vol. 57, No. 3, 2004, pp. 233-237. doi:10.1136/jcp.2003.007724
[17] M. Abdel-Hadi, G. F. Abdel-Hamid, N. Abdel-Razek and R. K. Fawzy, “Should Fine-Needle Aspiration Cytology Be the First Choice Diagnostic Modality for Assessment of All Nonpalpablebreast Lesions? The Experience of a Breast Cancer Screening Center in Alexandria, Egypt,” Diagnostic Cytopathology, Vol. 38, No. 12, 2010, pp. 880-889. doi:10.1002/dc.21305
[18] B. G. Beatty, R. Bryant, W. Wang, T. Ashikaga, P. C. Gibson, G. Leiman, et al., “HER-2/neu Detection in FineNeedle Aspirates of Breast Cancer: Fluorescence in Situ Hybridization and Immunocytochemical Analysis,” American Journal of Clinical Pathology, Vol. 122, No. 2, 2004, pp. 246-255.
[19] C. Bozzetti, R. Nizzoli, A. Guazzi, M. Flora, C. Bassano, P. Crafa, et al., “HER-2/neu Amplification Detected by Fluorescence in Situ Hybridization in Fine Needle Aspirates from Primary Breast Cancer,” Annals of Oncology, Vol. 13, No. 9, 2002, pp. 1398-1403. doi:10.1093/annonc/mdf217
[20] A. Mezzelani, L. Alasio, C. Bartoli, M. G. Bonora, M. A. Pierotti, F. Rilke, et al., “c-erbB2/neu Gene and Chromosome 17 Analysis in Breast Cancer by FISH on Archival Cytological Fine-Needle Aspirates,” British Journal of Cancer, Vol. 80, No. 3-4, 1999, pp. 519-525.
[21] D. T. McManus, A. H. Patterson, P. Maxwell, M. W. Humphreys and N. H. Anderson, “Fluorescence in Situ Hybridisation Detection of erbB2 Amplification in Breast Cancer Fine Needle Aspirates,” Molecular Pathology, Vol. 52, No. 2, 1999, pp. 75-77.
[22] G. Sauter, G. Feichter, J. Torhorst, H. Moch, H. Novotna, U. Wagner, et al., “Fluorescence in Situ Hybridization for Detecting erbB-2 Amplification in Breast Tumor Fine Needle Aspiration Biopsies,” Acta Cytologica, Vol. 40, No. 2, 1996, pp. 164-173.
[23] J. Klijanienko, J. Couturier, M. Galut, A. K. El-Naggar, Z. Maciorowski, E. Padoy, et al., “Detection and Quantitation by Fluorescence in Situ Hybridization (FISH) and Image Analysis of HER-2/neu Gene Amplification in Breast Cancer Fine-Needle Samples,” Cancer, Vol. 87, No. 5, 1999, pp. 312-318.
[24] A. M. Gown, “Current Issues in ER and HER2 Testing by IHC in Breast Cancer,” Modern Pathology, Vol. 21, No. S8-S15, 2008, p. 34.
[25] A. Thor, “Applications of Molecular Analysis to Small Biopsy and Cytology Specimens for Diagnosis and Targeted Therapy. HER2/neu (erbB2) Analysis on FNA Smears and Core Biopsies of Primary or Metastatic Breast Cancer,” PSC/USCAP, 2008. http://pathologyportal.org/97th/pdf/comp anion16h03.pdf
[26] M. F. Press, D. J. Slamon, K. J. Flom, J. Park, J. Y. Zhou and L. Bernstein, “Evaluation of HER-2/neu Gene Amplification and Overexpression: Comparison of Frequently Used Assay Methods in a Molecularly Characterized Cohort of Breast Cancer Specimens,” Journal of Clinical Oncology, Vol. 20, No. 14, 2002, pp. 3095-3105.
[27] K. I. Goud, S. Dayakar, K. Vijayalaxmi, S. J. Babu and P. V. Reddy, “Evaluation of HER-2/neu Status in Breast Cancer Specimens Using Immunohistochemistry (IHC) & Fluorescence In-Situ Hybridization (FISH) Assay,” Indian Journal of Medical Research, Vol. 135, No. 3, 2012, pp. 312-317.
[28] R. D. Mass, M. F. Press and S. Anderson, “Improved Survival Benefit from Herceptin (Trastuzumab) in Patients Selected by Fluorescence in Situ Hybridization (FISH) (Abstract),” Proc Am Soc Clin Oncol, Vol. 20, No. 22a, 2001.
[29] S. Kakar, N. Puangsuvan, J. M. Stevens, R. Serenas, G. Mangan, S. Sahai, et al., “HER-2/neu Assessment in Breast Cancer by Immunohistochemistry and Fluorescence in Situ Hybridization: Comparison of Results and Correlation with Survival,” Journal of Molecular Diagnostics, Vol. 5, No. 3, 2000, pp. 199-207.
[30] M. F. Press, L. Bernstein, P. A. Thomas, L. F. Meisner, J. Y. Zhou, Y. Ma, et al., “HER-2/neu Gene Amplification Characterized by Fluorescence in Situ Hybridization: Poor Prognosis in Node-Negative Breast Carcinomas,” Journal of Clinical Oncology, Vol. 15, No. 8, 1997, pp. 2894-2904.
[31] G. Pauletti, S. Dandekar, H. Rong, L. Ramos, H. Peng, R. Seshadri, et al., “Assessment of Methods for TissueBased Detection of the HER-2/neu Alteration in Human Breast Cancer: A Direct Comparison of Fluorescence in Situ Hybridization and Immunohistochemistry,” Journal of Clinical Oncology, Vol. 18, No. 21, 2000, pp. 3651-3664.
[32] C. L. Vogel, M. A. Cobleigh, D. Tripathy, J. C. Gutheil, L. N. Harris, L. Fehrenbacher, et al., “Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer,” Journal of Clinical Oncology, Vol. 20, No. 3, 2002, pp. 719-726.
[33] M. A. Cobleigh, C. L. Vogel, D. Tripathy, N. J. Robert, S. Scholl, L. Fehrenbacher, et al., “Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed after Chemotherapy for Metastatic Disease,” Journal of Clinical Oncology, Vol. 17, No. 9, 1999, pp. 2639-2648.
[34] T. W. Jacobs, A. M. Gown, H. Yaziji, M. J. Barnes and S. J. Schnitt, “Specificity of HercepTest in determining HER2/neu Status of Breast Cancers Using the United States Food and Drug Administration-Approved Scoring System,” Journal of Clinical Oncology, Vol. 17, No. 7, 1999, pp. 1983-1987.
[35] P. C. Roche and J. N. Ingle, “Increased HER2 with US Food and Drug Administration-Approved Antibody,” Journal of Clinical Oncology, Vol. 17, No. 1, 1999, p. 434.
[36] A. Lebeau, D. Deimling, C. Kaltz, A. Sendelhofert, A. Iff, B. Luthardt, et al., “Her-2/neu Analysis in Archival Tissue Samples of Human Breast Cancer: Comparison of Immunohistochemistry and Fluorescence in Situ Hybridization,” Journal of Clinical Oncology, Vol. 19, No. 2, 2001, pp. 354-363.

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.