The monoclonal antibody (MAb) SM-3, which was raised to chemically deglycosylated milk mucin, reacts with an epitope present on the core protein of this mucin which we have referred to as PEM (polymorphic epithelial mucin). Although this mucin is abundantly expressed by both the lactating breast and breast carcinomas, the antibody SM-3 shows very little or no reactivity on the former but does react with 92% of breast carcinomas. Furthermore, SM-3 stains primary carcinomas of the lung, colon and ovary, but on the corresponding normal tissue the epitope is expressed at a much reduced level or not at all. These results indicate that an epitope masked in the normal mucin is exposed in the mucin produced by tumour cells, perhaps due to aberrant glycosylation. An extensive immunohistochemical study of other normal tissues reveals that the majority show only weak focal staining with SM-3 or none at all, the distal tubules and collecting ducts of the kidney, and sebaceous glands being the only normal tissues studied to show homogeneously positive staining.

The adamalysin-thrombospondin (ADAMTS) proteinases are a relatively newly described branch of the metzincin family that contain metalloproteinase, disintegrin, and thrombospondin motifs. They have been implicated in various cellular events, including cleavage of proteoglycans, extracellular matrix degradation, inhibition of angiogenesis, gonadal development, and organogenesis. However, in many cases, their normal physiological roles and their potential for dysregulation in malignancy remain to be established. The expression profile of ADAMTS1-20 in human breast carcinoma was undertaken by real-time PCR using RNA isolated from malignant tumors, nonneoplastic mammary tissue, and breast cancer cell lines to identify altered regulation that may have potential pathogenetic and prognostic significance. Our studies show that seven of the ADAMTS genes (ADAMTS1, 3, 5, 8, 9, 10, and 18) are consistently downregulated in breast carcinomas with respect to nonneoplastic mammary tissue, irrespective of the heterogeneity of the samples and the tumor type or grade (Mann-Whitney U test, P < 0.0001 for each gene). Conversely, ADAMTS4, 6, 14, and 20 are consistently up-regulated in breast carcinomas (P ‫؍‬ 0.005, P < 0.0001, P ‫؍‬ 0.003, and P ‫؍‬ 0.001, respectively). ADAMTS2, 7, 12, 13, 15, 16, 17, and 19 show no significant difference between the sample types. ADAMTS1, 2, 7, 8, 10, and 12 are expressed predominantly in stromal fibroblasts. ADAMTS3, 4, 5, 6, 9, and 13-20 inclusive are expressed predominantly in myoepithelial cells; all appear to be relatively poorly expressed in luminal epithelial cells. ADAMTS15 has emerged as being an independent predictor of survival, with RNA expression levels significantly lower (P ‫؍‬ 0.007) in grade 3 breast carcinoma compared with grade 1 and 2 breast carcinoma.

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The aim of this study was to examine the relationship between mammographic density and histological characteristics of breast tumors within a case-control study population. This study was an expansion of a large size case-control study examining the relationship between breast density and breast cancer risk. Percent and area of breast density was assessed in 370 invasive breast cancer cases and 1904 age-matched controls, using a computer-assisted method. Associations between breast density and estrogen receptor (ER) status, histological grade, histological size, lymph node status, vascular invasion, disease extent, and Nottingham Prognostic Index were evaluated, using logistic regression. Women with 50% or greater mammographic density have a 2.63-fold risk (95% confidence interval [95% CI] = 1.78-3.87; p < 0.001) of developing breast cancer compared to women with less than 10% density. Increase in every category of percentage of breast density is also associated with a 1.45-fold risk in developing ER positive tumors relative to ER negative tumors (odds ratio [OR] = 1.02; 95% CI = 1.00-1.04; p = 0.048), and increase in every quartile of absolute area of density is associated with a 1.48-fold ER positive breast cancer risk [95% CI = 1.06-2.07; p = 0.020]. Furthermore, breast density was found to be associated with specifically ER positivity, invasion as well as invasion with in situ, histological grades 1 and 2, tumor size larger than 1.1 cm, lack of vascular invasion, lymph node positivity and negativity, and NPI less than 4.0. After stratifying the data according to mode of diagnosis, the relationship became slightly stronger in the interval cancer group. Similar results were in observed using percent density and absolute density readings. Mammographic density was a stronger risk factor for ER positive [OR = 2.94; 95% CI = 1.94-4.43; p < 0.001] than ER negative cancers when comparing breasts with greater than 50% dense region to those with less than 10% density. No other tumor characteristic had a significant correlation with breast density. These results suggest that mammographic percent density may be more strongly related to ER positive than ER negative breast cancer, but otherwise is a risk factor for breast cancer independent of other tumor characteristics.