Top

Published in:

01-09-2019 | Breast Cancer | Original Article

What to expect from the 2018 ASCO/CAP HER2 guideline in the reflex in situ hybridization test of immunohistochemically equivocal 2+ cases?

Authors: Mónica Curado, Ana Sofia Caramelo, Catarina Eloy, António Polónia

Published in: Virchows Archiv | Issue 3/2019

Abstract

To evaluate the effect of the 2018 ASCO/CAP guideline in the identification of HER2-positive breast carcinomas (BC) in reflex in situ hybridization (ISH) test. A total of 592 primary invasive BC cases from before and after the publication of the updated ASCO/CAP guideline were evaluated for HER2 amplification by silver ISH according to the 2013 and 2018 guidelines. Cases were mostly (95%) HER2 equivocal by immunohistochemistry (IHC), not centrally reviewed. Other reasons for referring cases were IHC confirmation, IHC discordancy (either between needle-core-biopsy (NCB) and surgical excision specimen (SES) or between different laboratories) and IHC result unexpected for histopathologic features. Cases evaluated with the 2013 guideline (1st cohort) were 14.6% HER2-positive, decreasing significantly after the reclassification with the 2018 guideline due to the exclusion of group 2 cases without HER2 protein overexpression. Cases studied after the implementation of the 2018 guideline (2nd cohort) were 8.7% HER2-positive, a frequency that was not significantly different from the reclassification of the 1st cohort with the 2018 guideline. All cases referred for IHC confirmation had the expected ISH result. Cases with IHC discordancy between NCB and SES were ISH concordant. Only one out of 14 cases with an IHC score 3+ and classified as histological grade 1 or with a Ki67 below 10% was classified as ISH HER2-positive. The 2018 ASCO/CAP guideline resulted in a decrease of HER2-positive cases in reflex ISH test, selecting less patients for anti-HER2-targeted therapy.

Available only for authorised users

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424CrossRef

Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, Bilous M, Ellis IO, Fitzgibbons P, Hanna W, Jenkins RB, Press MF, Spears PA, Vance GH, Viale G, McShane LM, Dowsett M (2018) Human epidermal growth factor receptor 2 testing in breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. Arch Pathol Lab Med 142(11):1364–1382CrossRef

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 (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 134(7):e48–e72

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182CrossRef

Press MF, Bernstein L, Thomas PA, Meisner LF, Zhou JY, Ma Y, Hung G, Robinson RA, Harris C, El-Naggar A, Slamon DJ, Phillips RN, Ross JS, Wolman SR, Flom KJ (1997) HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol 15(8):2894–2904CrossRef

Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792CrossRef

Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ (1999) 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. J Clin Oncol 17(9):2639–2648CrossRef

Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20(3):719–726CrossRef

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672CrossRef

10.

Press MF, Villalobos I, Santiago A, Guzman R, Cervantes M, Gasparyan A, Campeau A, Ma Y, Tsao-Wei DD, Groshen S (2016) Assessing the new American Society of Clinical Oncology/College of American Pathologists Guidelines for HER2 testing by fluorescence in situ hybridization: experience of an academic consultation practice. Arch Pathol Lab Med 140:1250–1258CrossRef

11.

Press MF, Sauter G, Buyse M, Fourmanoir H, Quinaux E, Tsao-Wei DD, Eiermann W, Robert N, Pienkowski T, Crown J, Martin M, Valero V, Mackey JR, Bee V, Ma Y, Villalobos I, Campeau A, Mirlacher M, Lindsay MA, Slamon DJ (2016) HER2 gene amplification testing by fluorescent in situ hybridization (FISH): comparison of the ASCO-College of American pathologists guidelines with FISH scores used for enrollment in breast Cancer international research group clinical trials. J Clin Oncol 34(29):3518–3528CrossRef

12.

Long TH, Lawce H, Durum C, Moore SR, Olson SB, Gatter K, Troxell ML (2015) The new equivocal: changes to HER2 FISH results when applying the 2013 ASCO/CAP guidelines. Am J Clin Pathol 144(2):253–262CrossRef

13.

Muller KE, Marotti JD, Memoli VA, Wells WA, Tafe LJ (2015) Impact of the 2013 ASCO/CAP HER2 guideline updates at an Academic Medical Center that performs primary HER2 FISH testing: increase in equivocal results and utility of reflex immunohistochemistry. Am J Clin Pathol 144(2):247–252CrossRef

14.

Varga Z, Noske A (2015) Impact of modified 2013 ASCO/CAP guidelines on HER2 testing in breast Cancer. One year experience. PLoS One 10(10):e0140652CrossRef

15.

Bethune GC, Veldhuijzen van Zanten D, MacIntosh RF, Rayson D, Younis T, Thompson K, Barnes PJ (2015) Impact of the 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing of invasive breast carcinoma: a focus on tumours assessed as 'equivocal' for HER2 gene amplification by fluorescence in-situ hybridization. Histopathology 67(6):880–887CrossRef

16.

Lim TH, Lim AS, Thike AA, Tien SL, Tan PH (2016) Implications of the updated 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations on human epidermal growth factor receptor 2 gene testing using immunohistochemistry and fluorescence in situ hybridization for breast Cancer. Arch Pathol Lab Med 140(2):140–147CrossRef

17.

Stoss OC, Scheel A, Nagelmeier I, Schildhaus HU, Henkel T, Viale G, Jasani B, Untch M, Ruschoff J (2015) Impact of updated HER2 testing guidelines in breast cancer--re-evaluation of HERA trial fluorescence in situ hybridization data. Mod Pathol 28(12):1528–1534CrossRef

18.

Hanna WM, Slodkowska E, Lu FI, Nafisi H, Nofech-Mozes S (2017) Comparative analysis of human epidermal growth factor receptor 2 testing in breast Cancer according to 2007 and 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations. J Clin Oncol 35(26):3039–3045CrossRef

19.

Shah MV, Wiktor AE, Meyer RG, Tenner KS, Ballman KV, Green SJ, Sukov WR, Ketterling RP, Perez EA, Jenkins RB (2016) Change in pattern of HER2 fluorescent in situ hybridization (FISH) results in breast cancers submitted for FISH testing: experience of a reference laboratory using US Food and Drug Administration criteria and American Society of Clinical Oncology and College of American Pathologists Guidelines. J Clin Oncol 34(29):3502–3510CrossRef

20.

Polonia A, Leitao D, Schmitt F (2016) Application of the 2013 ASCO/CAP guideline and the SISH technique for HER2 testing of breast cancer selects more patients for anti-HER2 treatment. Virchows Arch 468(4):417–423CrossRef

21.

Murray C, D'Arcy C, Gullo G, Flanagan L, Quinn CM, Quinn CM (2018) Human epidermal growth factor receptor 2 testing by fluorescent in situ hybridization: positive or negative? ASCO/College of American Pathologists Guidelines 2007, 2013, and 2018. J Clin Oncol 36(35):3522–3523

22.

Xu B, Shen J, Guo W, Zhao W, Zhuang Y, Wang L (2019) Impact of the 2018 ASCO/CAP HER2 guidelines update for HER2 testing by FISH in breast cancer. Pathol Res Pract 215(2):251–255CrossRef

23.

Wilkens L, Gerr H, Gadzicki D, Kreipe H, Schlegelberger B (2005) Standardised fluorescence in situ hybridisation in cytological and histological specimens. Virchows Arch 447(3):586–592CrossRef

24.

Starczynski J, Atkey N, Connelly Y, O'Grady T, Campbell FM, di Palma S, Wencyk P, Jasani B, Gandy M, Bartlett JM (2012) HER2 gene amplification in breast cancer: a rogues’ gallery of challenging diagnostic cases: UKNEQAS interpretation guidelines and research recommendations. Am J Clin Pathol 137(4):595–605CrossRef

25.

Dietel M, Ellis IO, Hofler H, Kreipe H, Moch H, Dankof A, Kolble K, Kristiansen G (2007) Comparison of automated silver enhanced in situ hybridisation (SISH) and fluorescence ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of American Pathologists. Virchows Arch 451(1):19–25CrossRef

26.

Shousha S, Peston D, Amo-Takyi B, Morgan M, Jasani B (2009) Evaluation of automated silver-enhanced in situ hybridization (SISH) for detection of HER2 gene amplification in breast carcinoma excision and core biopsy specimens. Histopathology 54(2):248–253CrossRef

27.

Bartlett JM, Campbell FM, Ibrahim M, Wencyk P, Ellis I, Kay E, Connolly Y, O'Grady A, Di Palma S, Starczynski J, Morgan JM, Jasani B, Miller K (2009) Chromogenic in situ hybridization: a multicenter study comparing silver in situ hybridization with FISH. Am J Clin Pathol 132(4):514–520CrossRef

28.

Papouchado BG, Myles J, Lloyd RV, Stoler M, Oliveira AM, Downs-Kelly E, Morey A, Bilous M, Nagle R, Prescott N, Wang L, Dragovich L, McElhinny A, Garcia CF, Ranger-Moore J, Free H, Powell W, Loftus M, Pettay J, Gaire F, Roberts C, Dietel M, Roche P, Grogan T, Tubbs R (2010) Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: comparison with FISH and assessment of interobserver reproducibility. Am J Surg Pathol 34(6):767–776CrossRef

29.

Koh YW, Lee HJ, Lee JW, Kang J, Gong G (2011) Dual-color silver-enhanced in situ hybridization for assessing HER2 gene amplification in breast cancer. Mod Pathol 24(6):794–800CrossRef

30.

Lee Y, Ryu Y, Jeong H, Chang H, Kim Y, Kim A (2012) Effectiveness of silver-enhanced in situ hybridization for evaluating HER2 gene status in invasive breast carcinoma: a comparative study. Arch Med Res 43(2):139–144CrossRef

31.

Park K, Han S, Kim JY, Kim HJ, Kwon JE, Gwak G (2012) Silver-enhanced in situ hybridization as an alternative to fluorescence in situ hybridization for assaying HER2 amplification in clinical breast Cancer. J Breast Cancer 14(4):276–282CrossRef

32.

Jacquemier J, Spyratos F, Esterni B, Mozziconacci MJ, Antoine M, Arnould L, Lizard S, Bertheau P, Lehmann-Che J, Fournier CB, Krieger S, Bibeau F, Lamy PJ, Chenard MP, Legrain M, Guinebretiere JM, Loussouarn D, Macgrogan G, Hostein I, Mathieu MC, Lacroix L, Valent A, Robin YM, Revillion F, Triki ML, Seaume A, Salomon AV, de Cremoux P, Portefaix G, Xerri L, Vacher S, Bieche I, Penault-Llorca F (2013) SISH/CISH or qPCR as alternative techniques to FISH for determination of HER2 amplification status on breast tumors core needle biopsies: a multicenter experience based on 840 cases. BMC Cancer 13:351CrossRef

33.

Lim SJ, Cantillep A, Carpenter PM (2013) Validation and workflow optimization of human epidermal growth factor receptor 2 testing using INFORM HER2 dual-color in situ hybridization. Hum Pathol 44(11):2590–2596CrossRef

34.

Unal B, Karaveli FS, Pestereli HE, Erdogan G (2013) Determination of HER2 gene amplification in breast cancer using dual-color silver enhanced in situ hybridization (dc- SISH) and comparison with fluorescence ISH (FISH). Asian Pac J Cancer Prev 14(10):6131–6134CrossRef

35.

Biserni GB, Engstrom MJ, Bofin AM (2016) HER2 gene copy number and breast cancer-specific survival. Histopathology 69(5):871–879CrossRef

36.

Press MF, Seoane JA, Curtis C, Quinaux E, Guzman R, Sauter G, Eiermann W, Mackey JR, Robert N, Pienkowski T, Crown J, Martin M, Valero V, Bee V, Ma Y, Villalobos I, Slamon DJ (2018) Assessment of ERBB2/HER2 status in HER2-equivocal breast cancers by FISH and 2013/2014 ASCO-CAP guidelines. JAMA Oncol 5(3):366–375

37.

Ballard M, Jalikis F, Krings G, Schmidt RA, Chen YY, Rendi MH, Dintzis SM, Jensen KC, West RB, Sibley RK, Troxell ML, Allison KH (2017) 'Non-classical' HER2 FISH results in breast cancer: a multi-institutional study. Mod Pathol 30(2):227–235CrossRef

38.

Nitta H, Hauss-Wegrzyniak B, Lehrkamp M, Murillo AE, Gaire F, Farrell M, Walk E, Penault-Llorca F, Kurosumi M, Dietel M, Wang L, Loftus M, Pettay J, Tubbs RR, Grogan TM (2008) Development of automated brightfield double in situ hybridization (BDISH) application for HER2 gene and chromosome 17 centromere (CEN 17) for breast carcinomas and an assay performance comparison to manual dual color HER2 fluorescence in situ hybridization (FISH). Diagn Pathol 3:41CrossRef

39.

Hanna W, Nofech-Mozes S, Kahn HJ (2007) Intratumoral heterogeneity of HER2/neu in breast cancer--a rare event. Breast J 13(2):122–129CrossRef

40.

Andersson J, Linderholm B, Bergh J, Elmberger G (2004) HER-2/neu (c-erbB-2) evaluation in primary breast carcinoma by fluorescent in situ hybridization and immunohistochemistry with special focus on intratumor heterogeneity and comparison of invasive and in situ components. Appl Immunohistochem Mol Morphol 12(1):14–20CrossRef

41.

Polonia A, Eloy C, Pinto J, Braga AC, Oliveira G, Schmitt F (2017) Counting invasive breast cancer cells in the HER2 silver in-situ hybridization test: how many cells are enough? Histopathology 71(2):247–257CrossRef

42.

Polonia A, Oliveira G, Schmitt F (2017) Characterization of HER2 gene amplification heterogeneity in invasive and in situ breast cancer using bright-field in situ hybridization. Virchows Arch 471(5):589–598CrossRef

43.

Martins D, Sousa B, Lopes N, Gomes M, Veronese L, Albergaria A, Paredes J, Schmitt F (2011) Molecular phenotypes of matched in situ and invasive components of breast carcinomas. Hum Pathol 42(10):1438–1446CrossRef

44.

Tamimi RM, Baer HJ, Marotti J, Galan M, Galaburda L, Fu Y, Deitz AC, Connolly JL, Schnitt SJ, Colditz GA, Collins LC (2008) Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer. Breast Cancer Res 10(4):R67CrossRef

45.

Rakha EA, Reis-Filho JS, Baehner F, Dabbs DJ, Decker T, Eusebi V, Fox SB, Ichihara S, Jacquemier J, Lakhani SR, Palacios J, Richardson AL, Schnitt SJ, Schmitt FC, Tan PH, Tse GM, Badve S (2010) Ellis IO breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res 12(4):207CrossRef

46.

Rakha EA, Ellis IO (2007) An overview of assessment of prognostic and predictive factors in breast cancer needle core biopsy specimens. J Clin Pathol 60(12):1300–1306CrossRef

47.

Dowsett M, Hanna WM, Kockx M, Penault-Llorca F, Ruschoff J, Gutjahr T, Habben K, van de Vijver MJ (2007) Standardization of HER2 testing: results of an international proficiency-testing ring study. Mod Pathol 20(5):584–591CrossRef

48.

Rakha EA, Pinder SE, Bartlett JM, Ibrahim M, Starczynski J, Carder PJ, Provenzano E, Hanby A, Hales S, Lee AH, Ellis IO (2015) Updated UK recommendations for HER2 assessment in breast cancer. J Clin Pathol 68(2):93–99CrossRef

49.

Tse CH, Hwang HC, Goldstein LC, Kandalaft PL, Wiley JC, Kussick SJ, Gown AM (2011) Determining true HER2 gene status in breast cancers with polysomy by using alternative chromosome 17 reference genes: implications for anti-HER2 targeted therapy. J Clin Oncol 29(31):4168–4174CrossRef

50.

Donaldson AR, Shetty S, Wang Z, Rivera CL, Portier BP, Budd GT, Downs-Kelly E, Lanigan CP, Calhoun BC (2017) Impact of an alternative chromosome 17 probe and the 2013 American Society of Clinical Oncology and College of American Pathologists guidelines on fluorescence in situ hybridization for the determination of HER2 gene amplification in breast cancer. Cancer 123(12):2230–2239CrossRef

51.

Cancer Genome Atlas N (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70CrossRef

52.

Ma CX, Bose R, Gao F, Freedman RA, Telli ML, Kimmick G, Winer E, Naughton M, Goetz MP, Russell C, Tripathy D, Cobleigh M, Forero A, Pluard TJ, Anders C, Niravath PA, Thomas S, Anderson J, Bumb C, Banks KC, Lanman RB, Bryce R, Lalani AS, Pfeifer J, Hayes DF, Pegram M, Blackwell K, Bedard PL, Al-Kateb H, Ellis MJC (2017) Neratinib efficacy and circulating tumor DNA detection of HER2 mutations in HER2 nonamplified metastatic breast Cancer. Clin Cancer Res 23(19):5687–5695CrossRef

Title: What to expect from the 2018 ASCO/CAP HER2 guideline in the reflex in situ hybridization test of immunohistochemically equivocal 2+ cases?
Authors: Mónica Curado
Ana Sofia Caramelo
Catarina Eloy
António Polónia
Publication date: 01-09-2019
Publisher: Springer Berlin Heidelberg
Keywords: Breast Cancer
Breast Cancer
Published in: Virchows Archiv / Issue 3/2019
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-019-02567-z

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

What to expect from the 2018 ASCO/CAP HER2 guideline in the reflex in situ hybridization test of immunohistochemically equivocal 2+ cases?

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2019

Spread through air spaces (STAS) is a predictor of poor outcome in atypical carcinoids of the lung

Microfluidic-based immunohistochemistry for breast cancer diagnosis: a comparative clinical study

CD39 downregulation in chronic intervillositis of unknown etiology

Disease heterogeneity in IgG4-related hypophysitis: report of two histopathologically proven cases and review of the literature

Prognostic significance of histological categorization of desmoplastic reaction in colorectal liver metastases

Spindle cell liposarcoma with a TRIO-TERT fusion transcript