Study on breast carcinoma Her2/neu and hormonal receptors status assessed by automated images analysis systems: ACIS III (Dako) and ScanScope (Aperio).

UNLABELLED Her-2/neu is overexpressed in 20-30% of breast cancer patients and is associated with a more aggressive disease. Identification of Her-2/c-erbB-2-neu overexpression is based on immunohistochemical [ihc] detection of protein and/or gene amplification in fluorescence in situ hybridization test (FISH). Also Estrogen receptors [ER] and Progesterone receptors [PR] are the prognostic and predictive biomarkers, recently analysed by ihc methods. Subjective, manual scoring of the ihc Her-2/neu expression and expression of the ER/PR reported as the percentage of immunopositive cells are the most common mode of interpretation among pathologists. Automated microscopy and computerised processing have provided increased accuracy in quantification and standardisation. THE AIMS OF OUR STUDY WERE to evaluate the scoring reproducibility of Her-2 /neu ihc expression tested by two automated systems: ACIS (Dako) and ScanScope (Aperio); to estimate the ER/PR expression in ihc staining methods with different anti-ER/anti-PR antibodies (the monoclonal and the ER/PR pharmDx TM Kit) by the ACIS system. Her-2/neu ihc expression was measured in 114 primary invasive breast carcinomas by the manual and the automated scoring (ACIS and Aperio system). 106 slides stained ihc with two types of anti-ER/anti-PR antibodies entered the quantisation. The results of our investigations showed very high reproducibility of Her-2/neu scores in intra- and interobserver analysis by ACIS evaluation. The major concordance was present in strong 3+ ihc cases; very small discordance was shown by cases with low expression of Her-2/neu. The accuracy of scoring by the Aperio was little lower in comparison to ACIS but it might result from the smaller and variable series of samples analysed by Aperio. The concordance in scoring of two automated systems was 86.5% (p<0.0001; gamma=0.887); the discordance was referred only to the lower expression of Her-2/neu. The concordance in manual scoring performed by the single observer and the panel was 84.2% (p<0.0001, gamma = 0.99); the discordance comprised a few cases with strong expression (2+ vs 3+). Very high intra- and interobserver reproducibility of the ER/PR ihc measurements was present in the readers results (referred to the percentage of immunoreactive carcinomatous cell population in the breast carcinomas acc. to the ACIS algorithm). No differences were disclosed in the percentage of ER-immunoreactive and PR-immunoreactive carcinomatous cell populations when used 2 different type of antibodies, in the ACIS automated method.

[1]  C. Geyer,et al.  Solving the dilemma of the immunohistochemical and other methods used for scoring estrogen receptor and progesterone receptor in patients with invasive breast carcinoma , 2005, Cancer.

[2]  Rafael Rocha,et al.  Rabbit monoclonal antibodies show higher sensitivity than mouse monoclonals for estrogen and progesterone receptor evaluation in breast cancer by immunohistochemistry. , 2008, Pathology, research and practice.

[3]  P. Thomas,et al.  Comparison of immunohistochemistry by automated cellular imaging system (ACIS) versus fluorescence in‐situ hybridization in the evaluation of HER‐2/neu expression in primary breast carcinoma , 2006, Histopathology.

[4]  K. Bloom,et al.  Enhanced accuracy and reliability of HER-2/neu immunohistochemical scoring using digital microscopy. , 2004, American journal of clinical pathology.

[5]  D. Allred,et al.  Prognostic and predictive factors in breast cancer by immunohistochemical analysis. , 1998, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[6]  D. Slamon,et al.  HER2 testing and correlation with efficacy of trastuzumab therapy. , 2002, Oncology.

[7]  M. Kurosumi.  Immunohistochemical assessment of hormone receptor status using a new scoring system (J-score) in breast cancer , 2007, Breast cancer.

[8]  N. Sneige,et al.  Interobserver agreement for estrogen receptor immunohistochemical analysis in breast cancer: a comparison of manual and computer-assisted scoring methods. , 2004, Annals of diagnostic pathology.

[9]  Clive R Taylor,et al.  Recommendations for Improved Standardization of Immunohistochemistry , 2007, Applied immunohistochemistry & molecular morphology : AIMM.

[10]  William M Gallagher,et al.  Novel image analysis approach for quantifying expression of nuclear proteins assessed by immunohistochemistry: application to measurement of oestrogen and progesterone receptor levels in breast cancer , 2008, Breast Cancer Research.

[11]  Y. Yagi,et al.  Histology, imaging and new diagnostic work-flows in pathology , 2008, Diagnostic pathology.

[12]  Peter Devilee,et al.  Pathology and Genetics of Tumours of the Breast and Female Genital Organs , 2003 .

[13]  J. Bancroft,et al.  Theory and Practice of Histological Techniques , 1990 .

[14]  Marcial García-Rojo,et al.  Serendipia: Castilla-La Mancha telepathology network , 2008, Diagnostic pathology.

[15]  Jacques Ferlay,et al.  Estimating the world cancer burden: Globocan 2000 , 2001, International journal of cancer.

[16]  D. Edwards,et al.  Comparison of different antibodies for detection of progesterone receptor in breast cancer , 2002, Steroids.

[17]  J. Horiguchi,et al.  The effects of fixation, processing and evaluation criteria on immunohistochemical detection of hormone receptors in breast cancer , 2007, Breast cancer.

[18]  Jinsong Liu,et al.  Assessment of Two Automated Imaging Systems in Evaluating Estrogen Receptor Status in Breast Carcinoma , 2007, Applied immunohistochemistry & molecular morphology : AIMM.

[19]  M. Gnant,et al.  Evaluation of the United States Food and Drug Administration-approved scoring and test system of HER-2 protein expression in breast cancer. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[20]  C. Shimizu,et al.  Immunohistochemical evaluation for hormone receptors in Breast Cancer: A practically useful evaluation system and handling protocol , 2006, Breast cancer.

[21]  S H Barsky,et al.  Semi‐automated imaging system to quantitate estrogen and progesterone receptor immunoreactivity in human breast cancer , 2007, Journal of microscopy.

[22]  E. Frenkel,et al.  Assessment of HER-2/neu status in breast cancer. Automated Cellular Imaging System (ACIS)-assisted quantitation of immunohistochemical assay achieves high accuracy in comparison with fluorescence in situ hybridization assay as the standard. , 2001, American journal of clinical pathology.