Background:Optimization of workflow for breast cancer samples with equivocal human epidermal growth factor receptors 2 (HER2)/neu score 2+ results in routine practice, remains to be a central focus of the on-going efforts to assess HER2 status. According to the College of American Pathologists/American Society of Clinical Oncology guidelines equivocal HER2/neu score 2+ cases are subject for further testing, usually by fluorescence in situ hybridization (FISH) investigations. It still remains on open question, whether quantitative digital image analysis of HER2 immunohistochemistry (IHC) stained slides can assist in further refining the HER2 score 2+.Aim of this Work:To assess utility of quantitative digital analysis of IHC stained slides and compare its performance to FISH in cases of breast cancer with equivocal HER2 score 2+.Materials and Methods:Fifteen specimens (previously diagnosed as breast cancer and was evaluated as HER 2- score 2+) represented the study population. Contemporary new cuts were prepared for re-evaluation of HER2 immunohistochemical studies and FISH examination. All the cases were digitally scanned by iScan (Produced by BioImagene [Now Roche-Ventana]). The IHC signals of HER2 were measured using an automated image analyzing system (MECES, www.Diagnomx.eu/meces). Finally, a comparative study was done between the results of the FISH and the quantitative analysis of the virtual slides.Results:Three out of the 15 cases with equivocal HER2 score 2+, turned out to be positive (3+) by quantitative digital analysis, and 12 were found to be negative in FISH too. Two of these three positive cases proved to be positive with FISH, and only one was negative.Conclusions:Quantitative digital analysis is highly sensitive and relatively specific when compared to FISH in detecting HER2/neu overexpression. Therefore, it represents a potential reliable substitute for FISH in breast cancer cases, which desire further refinement of equivocal IHC results.

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BACKGROUND: Meningiomas are the most common primary tumors of the central nervous system worldwide. Routinely used immunohistochemical markers for diagnosis of confusing meningioma cases as epithelial membrane antigen lack specificity and sensitivity. MUC4 is glycosylated membrane-associated mucin expressed by normal epithelia and many cancers. However, it is recently noticed to be expressed in meningiomas. AIM: Intensity of MUC4 expression is needed to be verified whether it is the same among different subtypes or not. MATERIALS AND METHODS: Fifty cases of different intracranial meningioma subtypes and thirty cases of mesenchymal nonmeningothelial tumors were immunohistochemically stained with MUC4 antibody. The results of MUC4 expression intensity were associated with some clinical and pathological parameters. RESULTS: Most studied meningioma cases (84%) showed positive MUC4 expression. Meningothelial meningioma subtype showed characteristic pattern of diffuse and moderate to strong MUC4 staining. While fibroblastic meningioma showed mostly negative staining pattern and focal weak staining pattern if positive. A statistically significant relationship was detected between tumor subtype and intensity of MUC4 expression. On contrary, most included mesenchymal cases were MUC4 negative with statistical significance. Hence, the sensitivity of MUC4 as diagnostic marker for meningioma was 84%, while the specificity was 93.3%. Furthermore, meningioma histologic subtype showed significant relationship with age. CONCLUSION: The current study results suggest that MUC4 could be used as meningioma diagnostic marker with some limitations. Moreover, meningioma should be included in the differential diagnosis of MUC4 positive tumors.