Normal breast tissue

Trastuzumab is a monoclonal antibody directed against the HER-2/neu receptor. HER-2/neu is a member of the erbB (or HER) growth factor receptor family and is expressed at low levels in the epithelial cells of normal breast tissue. The overexpression of HER-2/neu is associated with increased transmission... 

Fig. 1. Indirect in situ RT-PCR for ras mRNA in normal and neoplastic human breast tissues. (A) and (C) Negative controls for ras message. (B) Detection of ras mRNA signal in normal epithelial cells of mammary duct and lobules. (D) Detection of ras mRNA signal in neoplastic ductal epithelial cells in breast tissue with ductal carcinoma in situ (DCIS).

R. E. Kast, G.K. Serhatkulu, A. Cao, et al., Raman spectroscopy can differentiate malignant tumors from normal breast tissue and detect early neoplastic changes in a mouse model. Biopolymers, 89, 235-241 (2008). 

Noseda A, Berens ME, White JG, Modest EJ (1988) In vitro antiproliferative activity of combinations of ether lipid analogues and DNA interactive agents against human tumor cells. Cancer Res 48 1788-1791 Obeid LM, Linardic CM, Karolak LA, Hannun YA (1993) Programmed cell death induced by ceramide. Science 259 1769-1771 O Brian CA, Vogel, VG, Singletary SE, Ward NE (1989a) Elevated protein kinase C expression in human breast tumor biopsies relative to normal breast tissue. Cancer Res 49 3215-3217... 

O Brian C, Vogel VG, Singletary SE, et al. Elevated protein kinase C expression in human breast tumor biopsies relative to normal breast tissue. Cancer Res 1989 49(12) 3215-3217. 

Mechanism of Action A testosterone derivative that suppresses the pituitary-ovarian axis by inhibiting the output of pituitary gonadotropins. Causes atrophy of both normal and ectopic endometrial tissue in endometriosis. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are depressed in fibrocystic breast disease. Inhibits steroid synthesis and binding of steroids to their receptors in breast tissues. Increases serum levels of esterase inhibitor. Therapeutic Effect Produces anovulation and amenorrhea, reduces the production of est rogen, corrects biochemical deficiency as seen in hereditary angioedema. 

Because biochemical methods used in the 1970s required large amounts of the tissue for homogenization, the studies concentrated on breast cancer (Fig. 11.1) rather than on normal breast (Fig. 11.2/Plate 5E). It was not until the development of antibodies against ER, which would be effective for the fixed tissue of a small size subjected to antigen retrieval, that normal breast tissue began to be analyzed for ER. 

Even today, a comparatively small number of studies are available on the ER in normal breast tissues. Consequently, we know much more about abnormal ER than about normal ER. Table 11.1 shows the presence of ER in a wide variety of carcinomas. 

HAP, COHAP and COD were measured through slabs of varying thickness from 2 to 10.2 mm of normal chicken breast tissue, and chicken breast with chicken skin on the surface. Chicken breast and skin tissue were used in the model due to their spectrally homogenous nature. Normal fresh chicken breast was obtained and a small section cut varying thicknesses between 2 and 10.2 mm (2.0, 3.1, 5.0, 5.9, 8.7, 10.2 mm) with other dimensions approximately 20 x 20mm. A small section of skin tissue was also cut (to 1.1mm thick). The samples were stored in a refrigerator and warmed to room temperature before use. 

Hudelist, G., Pacher-Zavisin, M., Singer, C.F., Holper, T., Kubista, E., Schreiber, M., Manavi, M., Bilban, M., and K. Czerwenka, 2004, Use of high-throughput protein array for profiling of differentially expressed proteins in normal and malignant breast tissue. Breast Cancer Res Treat. 86(3) 281-91. 

After acquiring a minimal amount of specimen, ranging from a few hundred to a few million cells, current proteomic analyses are able to generate MS patterns in a relatively short time span. In one study, less than 2 hours was needed to process human breast tissue that had been removed from the patient in the operating room until the MS data had been acquired. Mammary tissue containing normal breast epithelium and invasive carcinoma was compared, and over 40 peaks were identified that significantly differed in intensity [54]. This study employed LCM to acquire the tissue specimens. 

Bianchi E, Cohen RL, Thor AT, Todd RF, III, Mizukami IF, Lawrence DA, et al. The urokinase receptor is expressed in invasive breast cancer but not in normal breast tissue. Cancer Res 1994 54(4) 861-866. 

Figure 5. Over-digested (8-minute enzymatic digestion) FFPE breast tissue stained with gene probe (red), a centromere reference PNA probe (green) and DAPI (blue). The image shows doughnut formation and uneven DNA counter stain (blue). The arrow points to a nuclei with loss of red signal. The tissue specimen has a normal 1 1 gene to reference ratio at its optimal digestion time (3-minute enzymatic digestion — data not shown).

The DNA adducts, deoxyadenosine and deoxygua-nosine, which are induced by malondialdehyde, the end-product of lipid peroxidation, accumulate in human breast tissues. These adducts are present at relatively higher concentrations in breast cancer cells compared to normal breast cells. In a recent study, serum antioxidative vitamin levels and lipid peroxidation were compared in gastric cancer patients. The level of serum ascorbic acid, a-tocopherol, p-carotene, and retinol were assessed. The levels of ascorbic acid in patients with gastric carcinoma were less than one-fifth of that in the control group, and the production of p-carotene and a-tocopherol were decreased, as well. 

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