title: Computer Aided Semi-Automated Evaluation of HER2 Immunodetection--A Robust Solution for Supporting the Accuracy of Anti HER2 Therapy.
abstract: HER2-positive breast cancers usually benefit from anti-HER2 therapy, thus, HER2 evaluation became inevitable for patient selection. HER2-negative (IHC 0, 1+) and strong positive (IHC 3+) cases can easily be interpreted with immunohistochemistry, but equivocal (IHC 2+) cases require further analysis of HER2 gene amplification using in situ hybridization. Our study aimed to validate digital pathology and automated image analysis for unbiased evaluation of HER2 immunostains. We developed an image segmentation algorithm for analyzing HER2-immunostaining (4B5 clone) in tissue microarrays of breast cancers. Two pathologists assessed 309 microscopic regions of at least 100 tumor cells each--representing all HER2 positivity groups--according to international guidelines either semi-quantitatively or by using the MembraneQuant software. Scoring results were statistically correlated with each other and with FISH data, and almost perfect agreement was found (inter-method Cohen's kappa = 0.872, Spearman-rho = 0.928). When clinical relevance (scoring disagreement that may define erroneous treatment selection) was examined high agreement was found (quadratic weighted kappa = 0.967). Image analysis classified cases with excellent correlation with visual evaluation, therefore, MembraneQuant software proved to be a reliable tool for assessing HER2 immunoreactions and supporting better targeting anti-HER2 therapy. As digital analysis of immunomorphological markers allows permanent archiving, standardization and accurate reviewing of results, it supports quality assurance initiatives in diagnostic pathology--especially of equivocal cases which are hard to interpret.
authors: Ist Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085, Budapest, Üllöi u. 26, Hungary, micsikt@gmail.com.
authors: Tamás
authors: T
authors: Micsik
authors: Gábor
authors: G
authors: Kiszler
authors: Daniel
authors: D
authors: Szabó
authors: László
authors: L
authors: Krecsák
authors: Csaba
authors: C
authors: Hegedűs
authors: Krenács
authors: K
authors: Tibor
authors: Béla
authors: B
authors: Molnár
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000970:Antineoplastic Agents; D001331:Automation; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012984:Software; D046888:Tissue Array Analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human