Skip to main content
Erschienen in: Breast Cancer Research 6/2010

01.12.2010 | Editorial

Pre-analytic variables and phospho-specific antibodies: the Achilles heel of immunohistochemistry

verfasst von: Summar Siddiqui, David L Rimm

Erschienen in: Breast Cancer Research | Ausgabe 6/2010

Einloggen, um Zugang zu erhalten

Abstract

Immunohistochemistry is the most common method for companion diagnostic testing in breast cancer. The readings for estrogen receptor, progesterone receptor, and Her2 directly affect prescription of critical therapies. However, immunohistochemistry is highly sensitive to innumerable pre-analytic variables that result in loss of signal in these assays. Perhaps the most significant pre-analytic variable is cold ischemic time. The work of Pinhel and colleagues in the previous issue of Breast Cancer Research examines the effects of cold ischemic time and finds a chilling result. The authors show that while the classic markers may be only mildly affected, phospho-specific markers are highly sensitive to this artifact. As a result, it is likely that future companion diagnostic tests that include phospho-specific epitopes will be reliably done only in core needle biopsies that minimize ischemic time.
Literatur
1.
Zurück zum Zitat Pinhel IF, MacNeill FA, Hills MJ, Salter J, Detre S, A'Hern R, Nerurkar A, Osin P, Smith IE, Dowsett M: Extreme loss of immunoreactive p-Akt and p-Erk1/2 during routine fixation of primary breast cancer. Breast Cancer Res. 2010, 12: R76-10.1186/bcr2719.CrossRefPubMedPubMedCentral Pinhel IF, MacNeill FA, Hills MJ, Salter J, Detre S, A'Hern R, Nerurkar A, Osin P, Smith IE, Dowsett M: Extreme loss of immunoreactive p-Akt and p-Erk1/2 during routine fixation of primary breast cancer. Breast Cancer Res. 2010, 12: R76-10.1186/bcr2719.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Andersen JN, Sathyanarayanan S, Di Bacco A, Chi A, Zhang T, Chen AH, Dolinski B, Kraus M, Roberts B, Arthur W, Klinghoffer RA, Gargano D, Li L, Feldman I, Lynch B, Rush J, Hendrickson RC, Blume-Jensen P, Paweletz CP: Pathway-based identification of biomarkers for targeted therapeutics: personalized oncology with PI3K pathway inhibitors. Sci Transl Med. 2010, 2: 43ra55-PubMed Andersen JN, Sathyanarayanan S, Di Bacco A, Chi A, Zhang T, Chen AH, Dolinski B, Kraus M, Roberts B, Arthur W, Klinghoffer RA, Gargano D, Li L, Feldman I, Lynch B, Rush J, Hendrickson RC, Blume-Jensen P, Paweletz CP: Pathway-based identification of biomarkers for targeted therapeutics: personalized oncology with PI3K pathway inhibitors. Sci Transl Med. 2010, 2: 43ra55-PubMed
3.
Zurück zum Zitat Baker AF, Dragovich T, Ihle NT, Williams R, Fenoglio-Preiser C, Powis G: Stability of phosphoprotein as a biological marker of tumor signaling. Clin Cancer Res. 2005, 11: 4338-4340. 10.1158/1078-0432.CCR-05-0422.CrossRefPubMed Baker AF, Dragovich T, Ihle NT, Williams R, Fenoglio-Preiser C, Powis G: Stability of phosphoprotein as a biological marker of tumor signaling. Clin Cancer Res. 2005, 11: 4338-4340. 10.1158/1078-0432.CCR-05-0422.CrossRefPubMed
4.
Zurück zum Zitat Jones RJ, Boyce T, Fennell M, Jacobs V, Pinto F, Duffield E, Clack G, Green T, Kelly J, Robertson J: The impact of delay in cryo-fixation on biomarkers of Src tyrosine kinase activity in human breast and bladder cancers. Cancer Chemother Pharmacol. 2008, 61: 23-32. 10.1007/s00280-007-0440-9.CrossRefPubMed Jones RJ, Boyce T, Fennell M, Jacobs V, Pinto F, Duffield E, Clack G, Green T, Kelly J, Robertson J: The impact of delay in cryo-fixation on biomarkers of Src tyrosine kinase activity in human breast and bladder cancers. Cancer Chemother Pharmacol. 2008, 61: 23-32. 10.1007/s00280-007-0440-9.CrossRefPubMed
5.
Zurück zum Zitat Espina V, Edmiston KH, Heiby M, Pierobon M, Sciro M, Merritt B, Banks S, Deng J, VanMeter AJ, Geho DH, Pastore L, Sennesh J, Petricoin EF, Liotta LA: A portrait of tissue phosphoprotein stability in the clinical tissue procurement process. Mol Cell Proteomics. 2008, 7: 1998-2018. 10.1074/mcp.M700596-MCP200.CrossRefPubMedPubMedCentral Espina V, Edmiston KH, Heiby M, Pierobon M, Sciro M, Merritt B, Banks S, Deng J, VanMeter AJ, Geho DH, Pastore L, Sennesh J, Petricoin EF, Liotta LA: A portrait of tissue phosphoprotein stability in the clinical tissue procurement process. Mol Cell Proteomics. 2008, 7: 1998-2018. 10.1074/mcp.M700596-MCP200.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Hunter T: A thousand and one protein kinases. Cell. 1987, 50: 823-829. 10.1016/0092-8674(87)90509-5.CrossRefPubMed Hunter T: A thousand and one protein kinases. Cell. 1987, 50: 823-829. 10.1016/0092-8674(87)90509-5.CrossRefPubMed
7.
Zurück zum Zitat Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, American Society of Clinical Oncology; College of American Pathologists: 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 Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, American Society of Clinical Oncology; College of American Pathologists: 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
8.
Zurück zum Zitat Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC: 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: 907-922.PubMedPubMedCentral Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC: 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: 907-922.PubMedPubMedCentral
9.
Zurück zum Zitat Leyland-Jones BR, Ambrosone CB, Bartlett J, Ellis MJ, Enos RA, Raji A, Pins MR, Zujewski JA, Hewitt SM, Forbes JF, Abramovitz M, Braga S, Cardoso F, Harbeck N, Denkert C, Jewell SD, Breast International Group; Cooperative Groups of the Breast Cancer Intergroup of North America (TBCI); American College of Surgeons Oncology Group; Cancer and Leukemia Group B; Eastern Cooperative Oncology Group; North Central Cancer Treatment Group; National Cancer Institute of Canada Clinical Trials Group; Southwest Oncology Group; National Surgical Adjuvant Breast and Bowel Project; Radiation Oncology Group; Gynecologic Oncology Group; Children's Oncology Group: Recommendations for collection and handling of specimens from group breast cancer clinical trials. J Clin Oncol. 2008, 26: 5638-5644. 10.1200/JCO.2007.15.1712.CrossRefPubMedPubMedCentral Leyland-Jones BR, Ambrosone CB, Bartlett J, Ellis MJ, Enos RA, Raji A, Pins MR, Zujewski JA, Hewitt SM, Forbes JF, Abramovitz M, Braga S, Cardoso F, Harbeck N, Denkert C, Jewell SD, Breast International Group; Cooperative Groups of the Breast Cancer Intergroup of North America (TBCI); American College of Surgeons Oncology Group; Cancer and Leukemia Group B; Eastern Cooperative Oncology Group; North Central Cancer Treatment Group; National Cancer Institute of Canada Clinical Trials Group; Southwest Oncology Group; National Surgical Adjuvant Breast and Bowel Project; Radiation Oncology Group; Gynecologic Oncology Group; Children's Oncology Group: Recommendations for collection and handling of specimens from group breast cancer clinical trials. J Clin Oncol. 2008, 26: 5638-5644. 10.1200/JCO.2007.15.1712.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Goldstein NS, Ferkowicz M, Odish E, Mani A, Hastah F: Minimum formalin fixation time for consistent estrogen receptor immunohistochemical staining of invasive breast carcinoma. Am J Clin Pathol. 2003, 120: 86-92. 10.1309/QPHDRB00QXGMUQ9N.CrossRefPubMed Goldstein NS, Ferkowicz M, Odish E, Mani A, Hastah F: Minimum formalin fixation time for consistent estrogen receptor immunohistochemical staining of invasive breast carcinoma. Am J Clin Pathol. 2003, 120: 86-92. 10.1309/QPHDRB00QXGMUQ9N.CrossRefPubMed
11.
Zurück zum Zitat Rhodes A, Borthwick D, Sykes R, Al-Sam S, Paradiso A: The use of cell line standards to reduce HER-2/neu assay variation in multiple European cancer centers and the potential of automated image analysis to provide for more accurate cut points for predicting clinical response to trastuzumab. Am J Clin Pathol. 2004, 122: 51-60. 10.1309/E9B55JYHD84L8Y17.CrossRefPubMed Rhodes A, Borthwick D, Sykes R, Al-Sam S, Paradiso A: The use of cell line standards to reduce HER-2/neu assay variation in multiple European cancer centers and the potential of automated image analysis to provide for more accurate cut points for predicting clinical response to trastuzumab. Am J Clin Pathol. 2004, 122: 51-60. 10.1309/E9B55JYHD84L8Y17.CrossRefPubMed
12.
Zurück zum Zitat Khoury T, Sait S, Hwang H, Chandrasekhar R, Wilding G, Tan D, Kulkarni S: Delay to formalin fixation effect on breast biomarkers. Mod Pathol. 2009, 22: 1457-1467. 10.1038/modpathol.2009.117.CrossRefPubMed Khoury T, Sait S, Hwang H, Chandrasekhar R, Wilding G, Tan D, Kulkarni S: Delay to formalin fixation effect on breast biomarkers. Mod Pathol. 2009, 22: 1457-1467. 10.1038/modpathol.2009.117.CrossRefPubMed
Metadaten
Titel
Pre-analytic variables and phospho-specific antibodies: the Achilles heel of immunohistochemistry
verfasst von
Summar Siddiqui
David L Rimm
Publikationsdatum
01.12.2010
Verlag
BioMed Central
Erschienen in
Breast Cancer Research / Ausgabe 6/2010
Elektronische ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2782

Weitere Artikel der Ausgabe 6/2010

Breast Cancer Research 6/2010 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.