Skip to main content

Advertisement

SpringerLink
Log in

Molecular Pathology and Pre-Analytic Variables: Impact on Clinical Practice From a Breast Pathology Perspective

  • Molecular Pathology of Tumor Pre-Analytics (D Hicks, Section Editor)
  • Published:
Current Pathobiology Reports

Abstract

Purpose of Review

Cancer therapy is increasingly becoming dependent on the ability to target specific molecular pathways that drive disease progression. Consequently, the identification of specific molecular pathways requires the use of companion diagnostic assays that are accurate and reproducible. This review will discuss the data and concerns surrounding pre-analytic variables in the evaluation of breast cancer tissue.

Recent Findings

Although ASCO/CAP guidelines offer recommendations for the collection and preservation of diagnostic clinical tissues, standard clinical practice has paid little attention to the suitability of these tissues for further molecular analysis. Current research suggests that alterations in the molecular integrity of tissue during the pre-analytic stage may result in inaccurate results and potentially sub-standard patient care.

Summary

Threshold recommendations for optimal molecular analyses associated with pre-analytic variables are limited. Future recommendations regarding pre-analytic variables and molecular diagnostics of breast cancer tissue will require additional research on the effects of pre-fixation, fixation, processing, and storage on nucleic acid integrity, comparing fixed material with fresh and/or frozen controls.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hewitt SM, Badve SS, True LD. Impact of preanalytic factors on the design and application of integral biomarkers for directing patient therapy. Clin Cancer Res. 2012;18:1524–30. https://doi.org/10.1158/1078-0432.CCR-11-2204.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Parkinson B, Pearson SA, Viney R. Economic evaluations of trastuzumab in HER2-positive metastatic breast cancer: a systematic review and critique. Eur J Health Econ. 2014;15(1):93–112. https://doi.org/10.1007/s10198-013-0459-2.

    Article  PubMed  Google Scholar 

  3. Barron JJ, Cziraky MJ, Weisman T, Hicks DG. HER2 testing and subsequent trastuzumab treatment for breast cancer in a managed care environment. Oncologist. 2009;14(8):760–8. https://doi.org/10.1634/theoncologist.2008-0288.

    Article  PubMed  CAS  Google Scholar 

  4. Turner BM, Hicks DG. Pathologic diagnosis of breast cancer patients: evolution of the traditional clinical-pathologic paradigm toward “precision” cancer therapy. Biotech Histochem. 2017;92(3):175–200. https://doi.org/10.1080/10520295.2017.1290276.

    Article  PubMed  CAS  Google Scholar 

  5. Precision Medicine Initiative (PMI) Working Group Report to the Advisory Committee to the Director, NIH (2015) https://www.nih.gov/sites/default/files/research-training/initiatives/pmi/pmi-working-group-report-20150917-2.pdf Accessed 1 Feb 2018.

  6. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015;372(9):793–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Hicks DG. Targeted therapies in breast cancer: tailoring treatment to the molecular drivers of disease progression. MLO Med Lab Obs. 2012;44(1):36. 38-9

    PubMed  Google Scholar 

  8. Dietel M, Johrens K, Laffert MV, Bläker H, Pfitzner BM, Lehmann A, et al. A 2015 update on predictive molecular pathology and its role in targeted cancer therapy: a review focusing on clinical relevance. Cancer Gene Ther. 2015;22:417–30.

    Article  PubMed  CAS  Google Scholar 

  9. Hicks DG, Kulkarni S. HER2+ breast cancer: review of biologic relevance and optimal use of diagnostic tools. Am J Clin Pathol. 2008;129(2):263–73. https://doi.org/10.1309/99AE032R9FM8WND1.

    Article  PubMed  Google Scholar 

  10. Viale G. Pathological work up of the primary tumor: getting the proper information out of it. Breast. 2011;20(S3):S82–6. https://doi.org/10.1016/S0960-9776(11)70300-9.

    Article  PubMed  Google Scholar 

  11. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131:18–43.

    PubMed  CAS  Google Scholar 

  12. Wolff AC, Hammond MEH, Hicks DG, et al. Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. J Clin Oncol. 2013;31(31):3997–4013.

    Article  PubMed  Google Scholar 

  13. Hammond MEH, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med. 2010;134:907–22.

    PubMed  PubMed Central  Google Scholar 

  14. Hicks DG, Boyce BF. The challenge and importance of standardizing pre-analytical variables in surgical pathology specimens for clinical care and translational research. Biotech Histochem. 2012;87(1):14–7. https://doi.org/10.3109/10520295.2011.591832.

    Article  PubMed  CAS  Google Scholar 

  15. Payne DA, Baluchova K, Peoc’h KH, van Schaik RHN, Chan KCA, Maekawa M, et al. Pre-examination factors affecting molecular diagnostic test results and interpretation: a case-based approach. Clin Chim Acta. 2017;467:59–69. https://doi.org/10.1016/j.cca.2016.06.018.

    Article  PubMed  CAS  Google Scholar 

  16. Hicks DG, Kulkarni S, Hammond ME. The role of the indispensable surgical pathologist in treatment planning for breast cancer. Arch Pathol Lab Med. 2008;132(8):1226–7. https://doi.org/10.1043/1543-2165(2008)132[1226:TROTIS]2.0.CO;2.

  17. Moore HM, Compton CC, Alper J, Vaught JB. International approaches to advancing biospecimen science. Cancer Epidemiol Biomarkers Prev. 2011;20(5):729–32. https://doi.org/10.1158/1055-9965.EPI-11-0021.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Betsou F, Barnes R, Burke T, Coppola D, Desouza Y, Eliason J, et al. Human biospecimen research: experimental protocol and quality control tools. Cancer Epidemiol Biomark Prev. 2009;18(4):1017–25. https://doi.org/10.1158/1055-9965.EPI-08-1231.

    Article  Google Scholar 

  19. De Cecco L, Musella V, Veneroni S, Cappelletti V, Bongarzone I, Callari M, et al. Impact of biospecimens handling on biomarker research in breast cancer. BMC Cancer. 2009;9:409. https://doi.org/10.1186/1471-2407-9-409.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Bass BP, Engel KB, Greytak SR, Moore HM. A review of preanalytical factors affecting molecular, protein, and morphological analysis of formalin–fixed, paraffin–embedded (FFPE) tissue. Arch Pathol Lab Med. 2014;138(11):1520–30. https://doi.org/10.5858/arpa.2013-0691-RA.

    Article  PubMed  Google Scholar 

  21. Greytak SR, Engel KB, Bass BP, Moore HM. Accuracy of molecular data generated with FFPE biospecimens: lessons from the literature. Cancer Res. 2015;75(8):1541–7. https://doi.org/10.1158/0008-5472.CAN-14-2378.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Hicks DG: Preanalytic variable, tissue quality and clinical samples from breast cancer patients: implications for treatment planning, drug discovery and translational research. In: Badve S, Gökmen-Polar Y, editors. Molecular pathology of breast cancer. Spring; 2016. p. 19–26.

  23. Hicks DG, Kulkarni S. Transtuzumab as adjuvant therapy for early breast cancer: the importance of accurate human epidermal growth factor receptor 2 testing. Arch Pathol Lab Med. 2008a;132:1008–15. https://doi.org/10.1043/1543-2165(2008)132[1008:TAATFE]2.0.CO;2.

  24. Hicks DG. Standardization of tissue handling from the OR to the laboratory. AORN J. 2014;99(6):810–3.

    Article  PubMed  Google Scholar 

  25. Best S, Sawers Y, Fu VX, Almassi N, Huang W, Jarrard DF. Integrity of prostatic tissue for molecular analysis after robotic–assisted laparoscopic and open prostatectomy. Urology. 2007;70(2):328–32. https://doi.org/10.1016/j.urology.2007.04.005.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Khoury T, Sait S, Hwang H, Chandrasekhar R, Wilding G, Tan D, et al. Delay to formalin fixation effect on breast biomarkers. Mod Pathol. 2009 Nov;22(11):1457–67. https://doi.org/10.1038/modpathol.2009.117.

    Article  PubMed  CAS  Google Scholar 

  27. Petersen BL, Sørensen MC, Pedersen S, Rasmussen M. Fluorescence in situ hybridization on formalin-fixed and paraffin-embedded tissue: optimizing the method. Appl Immunohistochem Mol Morphol. 2004;12(3):259–65.

    Article  PubMed  Google Scholar 

  28. Lin J, Kawano H, Paparella MM, Ho SB. Improved RNA analysis for immediate autopsy of temporal bone soft tissues. Acta Otolaryngol. 1999;119(7):787–95.

    Article  PubMed  CAS  Google Scholar 

  29. Mizuno T, Nagamura H, Iwamoto KS, Ito T, Fukuhara T, Tokunaga M, et al. RNA from decades-old archival tissue blocks for retrospective studies. Diagn Mol Pathol. 1998;7(4):202–8.

    Article  PubMed  CAS  Google Scholar 

  30. Coudry RA, Meireles SI, Stoyanova R, Cooper HS, Carpino A, Wang X, et al. Successful application of microarray technology to microdissected formalin-fixed, paraffin-embedded tissue. J Mol Diagn. 2007;9(1):70–9. https://doi.org/10.2353/jmoldx.2007.060004.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Wickham CL, Sarsfield P, Joyner MV, Jones DB, Ellard S, Wilkins B. Formic acid decalcification of bone marrow trephines degrades DNA: alternative use of EDTA allows the amplification and sequencing of relatively long PCR products. Mol Pathol. 2000;53(6):336.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Alers JC, Krijtenburg PJ, Vissers KJ, van Dekken H. Effect of bone decalcification procedures on DNA in situ hybridization and comparative genomic hybridization. EDTA is highly preferable to a routinely used acid decalcifier. J Histochem Cytochem. 1999;47(5):703–10. https://doi.org/10.1177/002215549904700512.

    Article  PubMed  CAS  Google Scholar 

  33. Babic A, Loftin IR, Stanislaw S, Wang M, Miller R, Warren SM, et al. The impact of pre-analytical processing on staining quality for H&E, dual hapten, dual color in situ hybridization and fluorescent in situ hybridization assays. Methods. 2010;52(4):287–300. https://doi.org/10.1016/j.ymeth.2010.08.012.

    Article  PubMed  CAS  Google Scholar 

  34. Reineke T, Jenni B, Abdou MT, Frigerio S, Zubler P, Moch H, et al. Ultrasonic decalcification offers new perspectives for rapid FISH, DNA, and RT-PCR analysis in bone marrow trephines. Am J Surg Pathol. 2006;30(7):892–6. https://doi.org/10.1097/01.pas.0000213282.20166.13.

    Article  PubMed  Google Scholar 

  35. Arber JM, Weiss LM, Chang KL, Battifora H, Arber DA. The effect of decalcification on in situ hybridization. Mod Pathol. 1997;10(10):1009–14.

    PubMed  CAS  Google Scholar 

  36. Walsh L, Freemont AJ, Hoyland JA. The effect of tissue decalcification on mRNA retention within bone for in-situ hybridization studies. Int J Exp Pathol. 1993;74(3):237–41.

    PubMed  PubMed Central  CAS  Google Scholar 

  37. Liu H, Huang X, Zhang Y, Ye H, El Hamidi A, Kocjan G, et al. Archival fixed histologic and cytologic specimens including stained and unstained materials are amenable to RT-PCR. Diagn Mol Pathol. 2002;11(4):222–7.

    Article  PubMed  Google Scholar 

  38. Brown RS, Edwards J, Bartlett JW, Jones C, Dogan A. Routine acid decalcification of bone marrow samples can preserve DNA for FISH and CGH studies in metastatic prostate cancer. J Histochem Cytochem. 2002;50(1):113–5. https://doi.org/10.1177/002215540205000113.

    Article  PubMed  CAS  Google Scholar 

  39. Neubauer A, Neubauer B, He M, Effert P, Iglehart D, Frye RA, et al. Analysis of gene amplification in archival tissue by differential polymerase chain reaction. Oncogene. 1992;7(5):1019–25.

    PubMed  CAS  Google Scholar 

  40. Fox CH, Johnson FB, Whiting J, et al. Formaldehyde fixation. J Histochem Cytochem. 1985;33:845–53.

    Article  PubMed  CAS  Google Scholar 

  41. Walker JF: Formaldehyde, 3rd ed. Am Chem Soc Monograph Series. Reinhold, New York, 1964.

  42. Blum F: Der formaldehyd als antisepticum. Munch Med Wochenschr 1893, Aug; 601.

  43. Blum F. Der formaldehyd als hartungsmittel. Z Wiss. Mikrosc. 1983;10:314.

    Google Scholar 

  44. Blum F. Notix uber die Anwendung des Formaldehyds (Formol) als Hartungs-und Konservierungsmittel. Anat Anz. 1894;9:229.

    Google Scholar 

  45. Bethe A. Formaidehyd! Nicht Formol oder Formalin Anat Anz. 1896;11:358.

    Google Scholar 

  46. Goelz SE, Hamilton SR, Vogelstein B. Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. Biochem Biophys Res Commun 1985;130(1):118–126.

  47. Ferrer I, Armstrong J, Capellari S, Parchi P, Arzberger T, Bell J, et al. Effects of formalin fixation, paraffin embedding, and time of storage on DNA preservation in brain tissue: a BrainNet Europe study. Brain Pathol. 2007;17(3):297–303. https://doi.org/10.1111/j.1750-3639.2007.00073.x.

    Article  PubMed  CAS  Google Scholar 

  48. Buesa RJ. Histology without formalin? Ann Diagn Pathol. 2008;12(6):387–96.

    Article  PubMed  Google Scholar 

  49. World Health Organization International Agency Research on Cancer. (2006) Volume 88 Formaldehyde, 2-Butoxyethanol, and 1-tert-Butoxypropan-2-ol. In: IARC monographs on the evaluation of carcinogenic risk to humans. World Health Organization International Agency Research on Cancer. 2006. https://monographs.iarc.fr/ENG/Monographs/vol88/mono88.pdf Accessed 2 Feb 2018.

  50. Mathieson W, Marcon N, Antunes L, Ashford DA, Betsou F, Frasquilho SG, et al. A critical evaluation of the PAXgene tissue fixation system: morphology, immunohistochemistry, molecular biology, and proteomics. Am J Clin Pathol. 2016;146(1):25–40. https://doi.org/10.1093/ajcp/aqw023.

    Article  PubMed  CAS  Google Scholar 

  51. Taylor CR. Standardization in immunohistochemistry: the role of antigen retrieval and molecular morphology. Biotech Histochem. 2006;81(1):3–12. https://doi.org/10.1080/10520290600667866.

    Article  PubMed  CAS  Google Scholar 

  52. Yamashita S. Heat-induced antigen retrieval: mechanisms and application to histochemistry. Prog Histochem Cytochem. 2007;41(3):141–200. https://doi.org/10.1016/j.proghi.2006.09.001.

    Article  PubMed  CAS  Google Scholar 

  53. Salehi Z, Najafi M. RNA preservation and stabilization. Biochem Physiol. 2014;3:126.

    Google Scholar 

  54. Staff S, Kujala P, Karhu R, Rökman A, Ilvesaro J, Kares S, et al. Preservation of nucleic acid and tissue morphology in paraffin-embedded clinical samples: comparison of five molecular fixatives. J Clin Pathol. 2013;66(9):807–10. https://doi.org/10.1136/jclinpath-2012-201283.

    Article  PubMed  Google Scholar 

  55. Delfour C, Pascal R, Bret C, Berthe ML, Rochaix P, Kalfa N, et al. RCL2, a new fixative, preserves morphology and nucleic acid integrity in paraffin-embedded breast carcinoma and microdissected breast tumor cells. J Mol Diagn. 2006;8(2):157–69. https://doi.org/10.2353/jmoldx.2006.050105.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Lykidis D, Van Noorden S, Armstrong A, Spencer-Dene B, Li J, Zhuang Z, et al. Novel zinc-based fixative for high quality DNA, RNA and protein analysis. Nucleic Acids Res. 2007;35(12):e85. https://doi.org/10.1093/nar/gkm433.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Viertler C, Groelz D, Gündisch S, Kashofer K, Reischauer B, Riegman PH, et al. A new technology for stabilization of biomolecules in tissues for combined histological and molecular analyses. J Mol Diagn. 2012;14(5):458–66. https://doi.org/10.1016/j.jmoldx.2012.05.002.

    Article  PubMed  CAS  Google Scholar 

  58. Groelz D, Sobin L, Branton P, Compton C, Wyrich R, Rainen L. Non-formalin fixative versus formalin-fixed tissue: a comparison of histology and RNA quality. Exp Mol Pathol. 2013;94(1):188–94. https://doi.org/10.1016/j.yexmp.2012.07.002.

    Article  PubMed  CAS  Google Scholar 

  59. O'Leary JJ, Browne G, Landers RJ, et al. The importance of fixation procedures on DNA template and its suitability for solution-phase polymerase chain reaction and PCR in situ hybridization. Histochem J. 1994;26(4):337–46.

    Article  PubMed  CAS  Google Scholar 

  60. Jackson DP, Lewis FA, Taylor GR, et al. Tissue extraction of DNA and RNA and analysis by the polymerase chain reaction. J Clin Pathol. 1990;43(6):499–504.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Noguchi M, Furuya S, Takeuchi T, et al. Modified formalin and methanol fixation methods for molecular biological and morphological analyses. Pathol Int. 1997;47(10):685–91.

    Article  PubMed  CAS  Google Scholar 

  62. Comanescu M, Annaratone L, D'Armento G, et al. Critical steps in tissue processing in histopathology. Recent Pat DNA Gene Seq. 2012;6(1):22–32.

    Article  PubMed  CAS  Google Scholar 

  63. Fedorowicz G, Guerrero S, Wu TD, Modrusan Z. Microarray analysis of RNA extracted from formalin-fixed, paraffin-embedded and matched fresh-frozen ovarian adenocarcinomas. BMC Med Genet. 2009;2:23. https://doi.org/10.1186/1755-8794-2-23.

    Article  CAS  Google Scholar 

  64. Hsu HC, Peng SY, Shun CT. High quality of DNA retrieved for Southern blot hybridization from microwave-fixed, paraffin-embedded liver tissues. J Virol Methods. 1991;31(2–3):251–61.

    PubMed  CAS  Google Scholar 

  65. Ruijter ET, Miller GJ, Aalders TW, van de Kaa CA, Schalken JA, Debruyne FM, et al. Rapid microwave-stimulated fixation of entire prostatectomy specimens. Biomed-II MPC Study Group. J Pathol. 1997;183(3):369–75. https://doi.org/10.1002/(SICI)1096-9896(199711)183:3<369::AID-PATH929>3.0.CO;2-9.

    Article  PubMed  CAS  Google Scholar 

  66. Bödör C, Schmidt O, Csernus BRH, Szende B. DNA and RNA isolated from tissues processed by microwave-accelerated apparatus MFX-800-3 are suitable for subsequent PCR and Q-RT-PCR amplification. Pathol Oncol Res. 2007;13(2):149–52.

    Article  PubMed  Google Scholar 

  67. Chu WS, Liang Q, Tang Y, King R, Wong K, Gong M, et al. Ultrasound-accelerated tissue fixation/processing achieves superior morphology and macromolecule integrity with storage stability. J Histochem Cytochem. 2006;54(5):503–13. https://doi.org/10.1369/jhc.5A6802.2005.

    Article  PubMed  CAS  Google Scholar 

  68. Fracasso T, Heinrich M, Hohoff C, Brinkmann B, Pfeiffer H. Ultrasound-accelerated formalin fixation improves the preservation of nucleic acids extraction in histological sections. Int J Legal Med. 2009;123:521. https://doi.org/10.1007/s00414-009-0368-1.

    Article  PubMed  Google Scholar 

  69. Chu WS, Furusato B, Wong K, Sesterhenn IA, Mostofi FK, Wei MQ, et al. Ultrasound-accelerated formalin fixation of tissue improves morphology, antigen and mRNA preservation. Mod Pathol. 2005;18(6):850–63. https://doi.org/10.1038/modpathol.3800354.

    Article  PubMed  CAS  Google Scholar 

  70. Merkelbach S, Gehlen J, Handt S, Füzesi L. Novel enzyme immunoassay and optimized DNA extraction for the detection of polymerase-chain-reaction-amplified viral DNA from paraffin-embedded tissue. Am J Pathol. 1997;150(5):1537–46.

    PubMed  PubMed Central  CAS  Google Scholar 

  71. Coombs NJ, Gough AC, Primrose JN. Optimisation of DNA and RNA extraction from archival formalin-fixed tissue. Nucleic Acids Res. 1999;27(16):e12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Gall K, Pavelić J, Jadro-Santel D, et al. DNA amplification by polymerase chain reaction from brain tissues embedded in paraffin. Int J Exp Pathol. 1993;74(4):333–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  73. Greer CE, Wheeler CM, Manos MM. Sample preparation and PCR amplification from paraffin-embedded tissues. PCR Methods Appl. 1994;3(6):S113–22.

    Article  PubMed  CAS  Google Scholar 

  74. Hewett PJ, Firgaira F, Morley A. The influence of age of template DNA derived from archival tissue on the outcome of the polymerase chain reaction. Aust N Z J Surg. 1994;64(8):558–9.

    Article  PubMed  CAS  Google Scholar 

  75. Jaremko M, Justenhoven C, Abraham BK, Schroth W, Fritz P, Brod S, et al. MALDI-TOF MS and TaqMan assisted SNP genotyping of DNA isolated from formalin-fixed and paraffin-embedded tissues (FFPET). Hum Mutat. 2005;25(3):232–8. https://doi.org/10.1002/humu.20141.

    Article  PubMed  CAS  Google Scholar 

  76. Pavelić J, Gall-Troselj K, Bosnar MH, Kardum MM, Pavelić K. PCR amplification of DNA from archival specimens. A methodological approach. Neoplasma. 1996;43(2):75–81.

    PubMed  Google Scholar 

  77. Talaulikar D, Shadbolt B, McNiven M, Dahlstrom JE. DNA amplification from formalin-fixed decalcified paraffin-embedded bone marrow trephine specimens: does the duration of storage matter? Pathology. 2008;40(7):702–6. https://doi.org/10.1080/00313020802436410.

    Article  PubMed  CAS  Google Scholar 

  78. Godfrey TE, Kim SH, Chavira M, Ruff DW, Warren RS, Gray JW, et al. Quantitative mRNA expression analysis from formalin-fixed, paraffin-embedded tissues using 5′ nuclease quantitative reverse transcription-polymerase chain reaction. J Mol Diagn. 2000;2(2):84–91. doi: https://doi.org/10.1016/S1525-1578(10)60621-6.

  79. Guerrero RB, Batts KP, Brandhagen DJ, et al. Effects of formalin fixation and prolonged block storage on detection of hepatitis C virus RNA in liver tissue. Diagn Mol Pathol. 1997;6(5):277–81.

    Article  PubMed  CAS  Google Scholar 

  80. Xi Y, Nakajima G, Gavin E, Morris CG, Kudo K, Hayashi K, et al. Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA. 2007;13(10):1668–74. https://doi.org/10.1261/rna.642907.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Mohsin SK, Weiss H, Havighurst T, Clark GM, Berardo M, Roanh le D, et al. Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study. Mod Pathol 2004;17(12):1545–1554. doi: https://doi.org/10.1038/modpathol.3800229.

  82. Pinhel IF, Macneill FA, Hills MJ, Salter J, Detre S, A’hern R, et al. Extreme loss of immunoreactive p-Akt and p-Erk1/2 during routine fixation of primary breast cancer. Breast Cancer Res. 2010;12(5):R76. https://doi.org/10.1186/bcr2719.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Vassilakopoulou M, Parisi F, Siddiqui S, England AM, Zarella ER, Anagnostou V, et al. Preanalytical variables and phosphoepitope expression in FFPE tissue: quantitative epitope assessment after variable cold ischemic time. Lab Investig. 2015;95(3):334–41. https://doi.org/10.1038/labinvest.2014.139.

    Article  PubMed  CAS  Google Scholar 

  84. Espina V, Edmiston KH, Heiby M, Pierobon M, Sciro M, Merritt B, et al. A portrait of tissue phosphoprotein stability in the clinical tissue procurement process. Mol Cell Proteomics. 2008;7(10):1998–2018. https://doi.org/10.1074/mcp.M700596-MCP200.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Diaz LK, Sneige N. Estrogen receptor analysis for breast cancer: current issues keys to increasing testing accuracy. Adv Anat Pathol. 2005;12:10–9.

    Article  PubMed  CAS  Google Scholar 

  86. Yildiz-Aktas IZ, Dabbs DJ, Bhargava R. The effect of cold ischemic time on the immunohistochemical evaluation of estrogen receptor, progesterone receptor, and HER2 expression in invasive breast carcinoma. Mod Pathol. 2012;25(8):1098–105. https://doi.org/10.1038/modpathol.2012.59.

    Article  PubMed  CAS  Google Scholar 

  87. Portier BP, Wang Z, Downs-Kelly E, Rowe JJ, Patil D, Lanigan C, et al. Delay to formalin fixation ‘cold ischemia time’: effect on ERBB2 detection by in-situ hybridization and immunohistochemistry. Mod Pathol. 2013;26(1):1–9. https://doi.org/10.1038/modpathol.2012.123.

    Article  PubMed  CAS  Google Scholar 

  88. Neumeister VM, Anagnostou V, Siddiqui S, England AM, Zarrella ER, Vassilakopoulou M, et al. Quantitative assessment of effect of preanalytic cold ischemic time on protein expression in breast cancer tissues. J Natl Cancer Inst. 2012;104(23):1815–24. https://doi.org/10.1093/jnci/djs438.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Mann GB, Fahey VD, Feleppa F, Buchanan MR. Reliance on hormone receptor assays of surgical specimens may compromise outcome in patients with breast cancer. J Clin Oncol. 2005;23(22):5148–54. https://doi.org/10.1200/JCO.2005.02.076.

    Article  PubMed  Google Scholar 

  90. Hicks DG, Tubbs RR. Assessment of the HER2 status in breast cancer by fluorescence in situ hybridization: a technical review with interpretive guidelines. Hum Pathol. 2005;36(3):250–61. https://doi.org/10.1016/j.humpath.2004.11.010.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Surgical Pathology Unit, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA

    Bradley M. Turner, Ioana Moisini & David G. Hicks

Authors
  1. Bradley M. Turner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ioana Moisini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David G. Hicks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David G. Hicks.

Ethics declarations

Conflict of Interest

Dr. Hicks reports other from Genentech BioOncology, outside the submitted work.

Drs. Moisini and Turner have nothing to disclose.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Molecular Pathology of Tumor Pre-Analytics

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Turner, B.M., Moisini, I. & Hicks, D.G. Molecular Pathology and Pre-Analytic Variables: Impact on Clinical Practice From a Breast Pathology Perspective. Curr Pathobiol Rep 6, 125–134 (2018). https://doi.org/10.1007/s40139-018-0169-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40139-018-0169-7

Keywords

Search

Navigation