In situ clinical evidence that zinc levels are decreased in breast invasive ductal carcinoma
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Altered zinc levels in malignant cells versus their normal cells have important implications in the development and progression of several cancers. Prostate, pancreatic, and hepatocellular carcinomas exhibit consistent marked zinc decrease in situ in the malignant cells, and other cancers (such as kidney, lung, and thyroid) also exhibit decreased tissue zinc levels. However, zinc levels are increased in breast cancer tissue compared to breast normal tissue, and the contemporary dominant view is that zinc is increased in invasive ductal carcinoma. This has important implications regarding the role and effects of zinc in breast malignancy compared to other cancers, which caused us to initiate this study to either confirm or challenge the contemporary view of an increased zinc level in the invasive ductal malignant cells.
We employed dithizone staining of breast tissue sections and tissue cores to determine the relative in situ cellular zinc levels specifically in the invasive ductal malignant cells as compared to normal ductal epithelium. This approach had not been employed in any of the reported breast studies.
The results revealed that the zinc levels are consistently and markedly decreased in the ductal malignant cells as compared with higher prominent zinc levels in the normal ductal epithelium. Decreased zinc is evident in Grade 1 well-differentiated malignancy and in Grade 2 and Grade 3 carcinomas. Among the twenty-five cancer cases in this study, none exhibited increased zinc in the invasive ductal carcinoma compared to the zinc level in the normal ductal epithelium.
The decreased zinc levels in breast invasive ductal carcinoma is consistent with prostate, pancreatic, and liver carcinomas in which the decrease in zinc is a required event in the development of malignancy to prevent cytotoxicity that would result from the higher zinc levels in the normal cells. This new understanding requires a redirection in elucidating the mechanisms and factors regarding the regulation of zinc in breast cancer, its potential translational applications as possible biomarkers, and for treatment of breast invasive ductal carcinoma.
KeywordsBreast cancer Invasive ductal carcinoma Zinc In situ tissue analysis Prostate cancer Pancreatic ductal carcinoma Hepatocellular carcinoma Zinc cytotoxicity and carcinogenesis
We express our appreciation to Dr. Olga Ioffe (Department of Pathology University of Maryland School of Medicine) for the valuable information provided in the identification of the archived cases of breast cancer. We thank Ashley Cellini and Kimberly C. Tuttle (University of Maryland Greenebaum Cancer Center Pathology Biorepository and Research Core) in providing slides of the archived breast tissues. Some of the studies and data of the authors described in this report were supported by NIH Grants CA79903, CA93443, and DK42839.