Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification is found in about 20% of invasive breast cancers. It is a sole predictive marker for treatment benefits from HER2 targeted therapy and thus, HER2 testing is a routine practice for newly diagnosed breast cancer in pathology. Currently, HER2 immunohistochemistry (IHC) is used for a screening test, and in situ hybridization is used as a confirmation test for HER2 IHC equivocal cases. Since the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines on HER2 testing was first released in 2007, it has been updated to provide clear instructions for HER2 testing and accurate determination of HER2 status in breast cancer. During HER2 interpretation, some pitfalls such as intratumoral HER2 heterogeneity and increase in chromosome enumeration probe 17 signals may lead to inaccurate assessment of HER2 status. Moreover, HER2 status can be altered after neoadjuvant chemotherapy or during metastatic progression, due to biologic or methodologic issues. This review addresses recent updates of ASCO/CAP guidelines and factors complicating in the interpretation of HER2 status in breast cancers.
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Background The aim of this study was to determine the regional heterogeneity and clinicopathological significance of microRNA-21 (miR-21) in advanced colorectal cancer (CRC) patients with distant metastasis.
Methods miR-21 expression was investigated by using locked nucleic acid– fluorescence in situ hybridization in the center and periphery of the primary cancer and in distant metastasis from 170 patients with advanced CRC. In addition, α-smooth muscle actin and desmin were evaluated to identify cancer-associated fibroblasts (CAFs) by using immunohistochemistry.
Results The miR-21 signal was observed in the cancer stroma. The expression of miR-21 (a score of 1–4) in the center and periphery of the primary cancer and in distant metastasis was observed in specimens from 133 (78.2%), 105 (61.8%), and 91 (53.5%) patients, respectively. miR-21 expression was heterogeneous in advanced CRC. Discordance between miR-21 expression in the center of the primary cancer and either the periphery of the primary cancer or distant metastasis was 31.7% or 44.7%, respectively. miR-21 stromal expression in the periphery of the primary cancer was significantly associated with a better prognosis (p=.004). miR-21 expression was significantly associated with CAFs in the center of the primary cancer (p=.001) and distant metastases (p=.041).
Conclusions miR-21 expression is observed in cancer stroma related to the CAF quantity and frequently presents regional heterogeneity in CRC. Our findings indicate that the role of miR-21 in predicting prognosis may be controversial but provide a new perspective of miR-21 level measurement in cancer specimens.
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It is important to predict the prognosis of patient with cancer. Well known parameters predicting the prognosis are staged and degree of differentiation. Recently, the prognostic and diagnostic significance of silver-stained nucleolar organizer regions(Ag-NORs) and flow cytometric DNA analysis are introduced. This study aims to detect the diagnostic significance of Ag-NORs in breast lesions, and to correlate the number of Ag-NORs and cellular ploidies in breast carcinoma. In addition, the existence of heterogeneity according to the sample in the same patient is studied Sixty six paraffin blocks(two primary lesions and the two metastatic lymph nodes in 13 patients, and one primary lesion and one metastatic lymph node I 10 patients) of breast carcinoma, 30 paraffin blocks of fibroadenoma and 23 paraffin blocks of normal breast are studied. The numbe of Ag-NORs increase from normal breast(mean 1.45) through fibroadenoma(mean 1.60) to carcinoma(mean 2.43). It was significantly different between each lsions(P<0.0005). The number of Ag-NORs increased in the aneuploidy carcinoma than that in the euploidy one(P<0.05). But, there was difference between the number of Ag-NORs and DNA index according to the sample area in the same patient with carcinoma. In conclusion, the number of Ag-NORs is diagnostically significant in breast lesions and is correlated with cellular ploidies in breast carcinoma. In addition, Ag-NORs and cellular ploidies are heterogenous in the same patient.