Mean Nuclear Area and Metallothionein Expression in Ductal Breast Tumors: Correlation With Estrogen Receptor Status

El-Sharkawy, Sonia Labib; Farrag, Ashraf

doi:10.1097/pai.0b013e31806d9b88

Cited by 14 publications

(12 citation statements)

References 18 publications

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“…Compared to non-malignant tissues, significantly higher MT staining was identified in gallbladder cancer [91], a significant decrease in colorectal [92] and cervical [93] tumors and no associations were observed in ductal breast tumors [94] and glioblastomas [95]. Immunohistochemical-based studies of other tumors were not identified.…”

Section: Resultsmentioning

confidence: 86%

Metallothionein – Immunohistochemical Cancer Biomarker: A Meta-Analysis

et al. 2014

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Metallothionein (MT) has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review.Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013) and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger's tests.A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls). A significantly positive association between MT staining and tumors (vs. healthy tissues) was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82–17.03) and ovarian tumors (OR 7.83; 1.09–56.29), and a negative association was ascertained in liver tumors (OR 0.10; 0.03–0.30). No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08–2.30). In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03–2.46), particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47–2.81). However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer.Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of head and neck, ovary and liver and in relation to the tumor grade and patient survival.

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Section: Resultsmentioning

confidence: 86%

Metallothionein – Immunohistochemical Cancer Biomarker: A Meta-Analysis

et al. 2014

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“…In Ref. [6], automatic measurements of mean nuclear area in breast cancer cells were performed using an advanced image processing and analysis system. Similarly in Ref.…”

Section: Resultsmentioning

confidence: 99%

Noninvasive Evaluation of Nuclear Morphometry in Breast Lesions Using Multispectral Diffuse Optical Tomography

et al. 2012

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Breast cancer is the most prevalent cancer and the main cause of cancer-related death in women worldwide. There are limitations associated with the existing clinical tools for breast cancer detection and alternative modalities for early detection and classification of breast cancer are urgently needed. Here we describe an optical imaging technique, called multispectral diffuse optical tomography (DOT), and demonstrate its ability of non-invasively evaluating nuclear morphometry for differentiating benign from malignant lesions. Photon densities along the surface of the breast were measured to allow for the extraction of three statistical parameters including the size, elongation and density of nuclei inside the breast tissue. The results from 14 patients (4 malignant and 10 benign lesions) show that there exist significant contrasts between the diseased and surrounding normal nuclei and that the recovered nuclear morphological parameters agree well the pathological findings. We found that the nuclei of cancer cells were less-spherical compared with those of surrounding normal cells, while the nuclear density or volume fraction provided the highest contrast among the three statistical parameters recovered. This pilot study demonstrates the potential of multispectral DOT as a cellular imaging method for accurate determination of breast cancer.

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“…In humans, breast tumor MT overexpression is associated with a poorer prognosis (Jin et al 2004). A remarkably clear correlation exists in breast tumors between MT overexpression and poor ER expression (El Sharkawy and Farrag 2008), indicating that increased MT may be another basal-like phenotype marker. Tissues often accumulate cadmium associated with MT (Cherian et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Cadmium Malignantly Transforms Normal Human Breast Epithelial Cells into a Basal-like Phenotype

Benbrahim‐Tallaa

Tokar

Diwan

et al. 2009

Environ Health Perspect

123

110

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BackgroundBreast cancer has recently been linked to cadmium exposure. Although not uniformly supported, it is hypothesized that cadmium acts as a metalloestrogenic carcinogen via the estrogen receptor (ER). Thus, we studied the effects of chronic exposure to cadmium on the normal human breast epithelial cell line MCF-10A, which is ER-negative but can convert to ER-positive during malignant transformation.MethodsCells were continuously exposed to low-level cadmium (2.5 μM) and checked in vitro and by xenograft study for signs of malignant transformation. Transformant cells were molecularly characterized by protein and transcript analysis of key genes in breast cancer.ResultsOver 40 weeks of cadmium exposure, cells showed increasing secretion of matrix metalloproteinase-9, loss of contact inhibition, increased colony formation, and increasing invasion, all typical for cancer cells. Inoculation of cadmium-treated cells into mice produced invasive, metastatic anaplastic carcinoma with myoepithelial components. These cadmium-transformed breast epithelial (CTBE) cells displayed characteristics of basal-like breast carcinoma, including ER-α negativity and HER2 (human epidermal growth factor receptor 2) negativity, reduced expression of BRCA1 (breast cancer susceptibility gene 1), and increased CK5 (cytokeratin 5) and p63 expression. CK5 and p63, both breast stem cell markers, were prominently overexpressed in CTBE cell mounds, indicative of persistent proliferation. CTBE cells showed global DNA hypomethylation and c-myc and k-ras overexpression, typical in aggressive breast cancers. CTBE cell xenograft tumors were also ER-α negative.ConclusionsCadmium malignantly transforms normal human breast epithelial cells—through a mechanism not requiring ER-α—into a basal-like cancer phenotype. Direct cadmium induction of a malignant phenotype in human breast epithelial cells strongly fortifies a potential role in breast cancer.

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Mean Nuclear Area and Metallothionein Expression in Ductal Breast Tumors: Correlation With Estrogen Receptor Status

Cited by 14 publications

References 18 publications

Metallothionein – Immunohistochemical Cancer Biomarker: A Meta-Analysis

Metallothionein – Immunohistochemical Cancer Biomarker: A Meta-Analysis

Noninvasive Evaluation of Nuclear Morphometry in Breast Lesions Using Multispectral Diffuse Optical Tomography

Cadmium Malignantly Transforms Normal Human Breast Epithelial Cells into a Basal-like Phenotype

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