植物相关人肿瘤抗原在乳腺癌中表达的研究

目的　检测一种植物相关人肿瘤抗原在乳腺癌、乳腺良性病变和正常乳腺组织中的表达 ,并探讨其临床意义。方法　采用S P免疫组织化学方法 ,检测该抗原在 5例正常乳腺组织、2 0例乳腺纤维腺瘤和 136例原发性乳腺癌中的表达。结果　植物相关人肿瘤抗原在乳腺正常组织中无表达 ;在乳腺纤维腺瘤中 ,表达阳性率为 2 0 .0 % ,且表达强度较低 ;在乳腺癌组织中 ,该抗原阳性表达率为 85 .3% ,与前两者相比 ,差异有极显著性 (P <0 .0 1) ,其表达水平与乳腺癌的组织学分级 (P <0 .0 5 )、浸润 (P <0 .0 1)和复发 (P <0 .0 5 )密切相关。结论　植物相关人肿瘤抗原在乳腺癌的发生发展过程中可能起重要作用 ,是一种具有潜在乳腺癌诊断价值的肿瘤标志物。     

A study of false positive and negative responses in the tube leucocyte adherence inhibition (tube LAI) assay.

A panel of 5 different breast-cancer and 2 other cancer extracts was used to clarify the false-negative responses in patients with Stage I and II breast cancer and the false-positive responses in control subjects. Most patients with Stage I and II breast cancer who had an initially negative LAI response were positive when tested against the panel. The false negatives occurred because of (1) the experimental errors of the assay; (2) changes in the antigenic strength of the extracts; (3) antigenic heterogeneity of a few tumours and (4) lack of tumour-specific reactivity of the host. 3% of control subjects had a false-positive LAI response. The leucocytes from most of these positive patients did not react to the panel of antigens, and hence the false positives appeared to result from experimental error. In-hospital patients with benign breast disease had a 12% positivity rate when initially assayed, and 63% of these patients reacted to the panel of breast-cancer antigens. Those patients with benign breast disease who reacted to the panel of breast-cancer antigens had cytophilic anti-breast-cancer antibody in their serum; their leucocyte LAI reactivity was blocked in an immunologically specific manner by serum from advanced Stage IV breast-cancer patients; their leucocytes reacted to extracts of breast cancer and not fibrocystic breast tissue; their leucocyte reactivity was blocked by isolated breast-cancer TSA that was linked to beta 2 microglobulin, but not by normal breast-tissue proteins; and the kinetics of the LAI response after excision of the breast mass was identical to that observed with breast-cancer patients after mastectomy. In these patients, the breast tissue within the breast lump expressed breast TSA similar to unequivocal breast cancer.     

Tissue binding of lectins in disorders of the breast

Twenty breast lesions including seven scirrhous ductal carcinomas, one infiltrating lobular carcinoma, one colloid carcinoma, four fibroadenomas, and seven cases of fibrocystic disease were analyzed by fluorescence microscopy for the presence and distribution of lectin-binding carbohydrates. Paraffin-embedded tissue sections were tested with wheat germ agglutinin (WGA), Ricin communis agglutinin I (RCA I), peanut agglutinin (PNA), Soybean agglutinin (SBA), Dolichos biflorus agglutinin (DBA), Ulex europaeus agglutinin I (UEA I), and concanavalin A (Con A). Brightest and most consistent staining regardless of the nature of the breast lesion was obtained with WGA followed in approximate order of staining intensity by RCA, PNA, SBA/DBA and Con A. UEA I stained many of the benign breast lesions but no malignant lesions. Lectin binding carbohydrate in benign lesions was localized mainly along the apices of mammary epithelial cells but there was considerable variation in staining patterns among malignant tumors. The fluorescence microscopic arrangement of lectin binding carbohydrate appears distinct for each malignant neoplasm of breast but is more consistent in benign conditions.     

乳腺癌演变过程中胰岛素样生长因子-1的表达和临床意义

目的：探讨胰岛素样生长因子-1（IGF-1）在乳腺癌演变过程中的表达变化规律和意义。方法：采用ELESIA方法检测28名健康女性,51例乳腺良性肿瘤患者,8例非典型增生患者,60例乳腺癌患者血清中IGF-1的表达水平;采用免疫组织化学方法检测30例正常乳腺组织,52例乳腺良性肿瘤组织、35例非典型增生组织、49例乳腺癌组织中IGF-1的表迭程度。结果：IGF-1在非典型增生组织中表达程度与在乳腺癌组织、乳腺良性肿瘤组织和正常组织相比呈高表迭,P值分别为0.0208、0.048和〈0.001。乳腺癌组织和良性肿瘤组织的IGF-1表达程度与正常乳腺组织相比呈高表达,P=0.0008,P=0.0004。非典型增生患者和乳腺癌患者血清中IGF-1表达水平与乳腺良性肿瘤患者血清和正常女性血清相比差异均有统计学意义,P=0.019;绝经前乳腺癌患者血清的IGF-1表达水平比绝经后乳腺癌患者的高,P=0.039。结论：IGF-1在乳腺癌的发生和演变过程中起重要作用。IGF-1可能在非典型增生组织向癌的转变过程中发挥关键作用。血清高水平的IGF-1可能与绝经前女性乳腺癌的发病风险增加有关。IGF-1可能为乳腺癌的发病风险预测和靶向治疗提供新的途径。     

Estrogen alpha and progesterone receptor expression in the normal mammary epithelium in relation to breast cancer risk

Estrogens play a central role in the etiology of breast cancer, and results from observational studies and randomized trials have also implicated progestins. The effects of these hormones in the mammary tissue are exerted through binding with specific receptor proteins in the cell nucleus. It has been proposed that higher estrogen receptor alpha expression in the normal breast epithelium may increase breast cancer risk. In a study in Greece, we determined estrogen alpha and progesterone receptor expression in normal mammary tissue adjacent to the pathological tissue from 267 women with breast cancer and 299 women with benign breast disease. Mouse monoclonal antibodies specific for estrogen receptor alpha and progesterone receptor were applied. The H-index, which incorporates frequency and intensity of staining of the cells, and can range from 0 to 300, was deemed positive when it exceeded 9. Among premenopausal women, there was no evidence for an association with breast cancer risk for expression of either type of receptors. Among postmenopausal women, breast cancer risk was inversely associated with expression of both estrogen alpha (odds ratio (OR)=0.39; p=0.015) and progesterone (OR=0.40; p=0.008) receptors. The hypothesis that overexpression of estrogen receptors alpha or progesterone receptors in normal breast epithelium may increase the risk of breast cancer was not supported by our data. Instead, we found evidence that overexpression of these receptors may be associated with reduced risk for breast cancer in line with the well-known association of expression of these receptors in the malignant tissue and better breast cancer prognosis.     

Serum levels and biochemical characteristics of cancer-associated antigen CA-549, a circulating breast cancer marker

CA-549 is a circulating breast cancer-associated antigen that reacts with monoclonal antibody BC4E 549. Biochemical characterization of CA-549 revealed that it is an acidic (isoelectric point 5.2) glycoprotein that exhibits two bands by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions of apparent molecular weights of 400,000 and 512,000. Immunohistochemical staining of unfixed frozen tissue sections of human breast tumors and a variety of benign tissues with BC4E 549 revealed no preferential staining of tumor over benign breast tissue and cross-reactivity with a wide range of other benign tissues including kidney, liver, lung, colon, pancreas, ovary, and spleen. Serum levels of CA-549 were initially tested by an enzyme-linked immunosorbent assay inhibition using BC4E 549. This assay showed that CA-549 concentrations were elevated in 19 of 27 sera from patients with advanced breast cancer compared to 0 of 22 and 0 of 129 sera from benign breast disease patients and healthy females, respectively. These preliminary data suggested that CA-549 was a useful breast tumor marker; thus BC4E 549 was adapted to a sandwich immunoradiometric assay format suitable for routine use in the clinical laboratory and its performance was evaluated on a panel of 668 serum samples. The test detected significant concentrations of CA-549 in the sera of 40 of 80 patients with advanced breast cancer, 1 of 30 with early breast cancer, 4 of 19 with advanced lung cancer, 2 of 40 with advanced colon cancer, and 5 of 29 with advanced prostate cancer. The test showed a high degree of specificity, producing false-positives in only 3 of 79 benign breast patients, 2 of 25 benign liver patients, 2 of 70 benign colon patients, 2 of 19 benign lung patients, 0 of 20 benign prostate patients, and 3 of 257 healthy individuals. These data represent an overall 50% sensitivity and 98% specificity as a test for advanced breast cancer. These data indicate that this immunoradiometric assay is a useful test for the detection of circulating CA-549 in advanced breast cancer patients and suggest that it may prove useful as a monitor in the management of that disease.     

Generation of monoclonal antibodies reactive with nuclear proteins of human primary breast tumors

Nuclear proteins were extracted from purified nuclei of human primary breast tumors (BrT) and bladder tumors and of human normal breast, kidney and lymphocytes by enzymatic treatment. SDS-Polyacrylamide gel electrophoresis of nuclear proteins from breast tumors showed different bands in the molecular weight zones from 25 to 220 kDa which were absent or present only as traces in normal breast tissue. Murine monoclonal antibodies (MAbs) have been produced using nuclear extracts of human primary breast tumors as immunogens. Approximately 2,000 hybridomas were generated from 5 hybridizations. According to their reactivity to BrT nuclear extracts and mammary carcinoma cell line MCF-7, seven hybridomas were selected and cloned. They were further characterized with histological immunoperoxidase assays of formaldehyde-fixed BrT paraffin tissue sections. MAb 6A3 particularly gave strong nuclear staining with all BrT specimens while MAb 1D8 showed both nuclear and cytoplasmic staining with only some of them. Specimens from mammoplasty did not react with these MAbs. Immunoblotting of BrT nuclear extracts as developed with MAbs 6A3 and 1D8 revealed major protein bands with molecular weight of 120 and 130 kDa. The potential use of these MAb-defined BrT-related nuclear proteins as markers for human breast cancer was suggested.     

HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer.

PURPOSE: The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer. PATIENTS AND METHODS: We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer. Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression. RESULTS: Among the controls, seven benign tissues (4.5%) demonstrated low-level HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18%) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio ?OR = 2.2; 95% confidence interval ?CI, 0.9 to 5.8); this association approached statistical significance. The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia. For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10% or more of epithelial cells, was found in 30% of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER-2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P =.06, Fisher's exact test). CONCLUSION: Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer.     

Aromatase activity in breast adipose tissue from women with benign and malignant breast diseases

In order to determine the significance of local oestrogen biosynthesis within the breast, aromatase activity has been measured in adipose tissue from the breasts of women with either benign (n = 36) or malignant breast disease (n = 51). Particulate fractions from all samples possessed aromatase activity, but levels in adipose tissue adjacent to malignant tumours were significantly higher than those in tissue close to benign breast lesions (P less than 0.0001). Elevated aromatase activity in adipose tissue from breast cancer patients may be of importance in view of the central role played by oestrogen in the natural history of breast cancer.     

Monoclonal antibody 323/A3: a marker for the presence of breast carcinoma

The monoclonal antibody 323/A3 has been suggested as a marker of cancer risk in benign breast disease. Patients who have had both a benign biopsy and a later biopsy for breast carcinoma were studied. The staining patterns in the biopsies were analysed using a semi-quantitative recording system adapted from Mariani-Costantini et al. Immunohistochemical (IHC) staining was carried out on formalin fixed paraffin embedded tissue sections. In apocrine metaplasia the cytoplasm of benign tissue did not stain with 323/A3 whereas in the biopsies with associated breast cancer 5 of 7 biopsies stained, a statistically significant difference. A positive predictive value of 100% was noted for strong cytoplasmic staining to indicate the presence of carcinoma and this phenomenon may be useful as a means of demonstrating patients who have malignant breast disease in which a biopsy has inadequately sampled the breast tissue.     

凝集素点印迹法分析胆汁糖蛋白糖链结构诊断胆管癌

目的：研究胆管癌胆汁中的肿瘤相关糖蛋白N－连接型糖链结构及其诊断价值。方法将31例胆管癌胆汁和13例良性胆道疾病胆汁直接点在硝酸膜（NC）上，采用辣根过氧化物酶（HRP）标记的刀豆凝集素（ConA)、欧曼陀罗凝集素（DSA）、麦胚凝集素（WGA）小豆凝集素（LCA）进行点印迹分析，结果胆管癌组和良性组ConA、DSA、LCA和WGA阳性率（阳性例／总例数）分别为80．6％（25．31％）和76．95（10．13）、74．2％（23／31）和0（0／13）、70．0％（22／31）和15．4％（2／13）、80．65（25／31）和23．1％（3／13），胆管癌组DSA、LCA和WGA阳性率高于良性组（P＜0．05）。结论胆管癌胆汁糖蛋白复杂型糖链增多，其核心岩藻糖和唾液酸含量丰富，可能出现偏二天线以及天线数的增加，胆汁糖蛋白的凝集素印迹分析法为胆管癌的诊断提供了新的有效方法。     

Elevated serum acute phase protein levels as predictors of disseminated breast cancer

Serum levels of four acute phase proteins, alpha 1-acid glycoprotein (AAGP), alpha 1-antitrypsin (AAT), haptoglobin (Hpt), and C3, were measured prior to biopsy in 38 women subsequently shown to have Stage I and II breast cancer and prior to treatment in 16 women with Stage IV disease. Sixty-one women with benign and 28 women with no breast disease served as controls. Mean serum levels of all four proteins were significantly elevated in women with stage IV disease as compared to women with Stage I or II disease or controls. Normal versus elevated levels for each protein were defined and AAGP was found to be the single most sensitive predictor of disseminated disease among the four. AAGP was elevated in 81.3% of Stage IV, 25% of Stage II, 14.3% of Stage I, and 12.4% of controls. Women with multiple proteins elevated were most likely to have advanced stage disease. Composite analysis of all four proteins using number of proteins abnormal or logistic regression analysis gave results similar to AAGP, both showing increasing numbers of proteins abnormal with increasing stage of breast cancer. These results indicate that measurement of serum acute phase proteins may be useful in initial staging of breast cancer patients and in following patients for indications of disseminated disease.     

Serum lipids and apolipoproteins in women with breast masses

Summary Background: Human mammary tissue metabolizes lipids from plasma, a process affected by female gonadal hormones. Both benign and malignant proliferation of breast tissue in women have been associated with changes in plasma lipid and lipoprotein levels.Methods: One hundred consecutive women with breast masses (50 malignant, 50 benign) had diagnostic biopsies followed by axillary node dissection in those with cancer. Fasting serum samples were taken just prior to biopsy and analyzed for lipid fatty acid and lipoprotein levels. Malignant breast tissue was analyzed for hormone receptor binding.Results: Low-density lipoprotein (LDL) components (total cholesterol, LDL-cholesterol, apolipoprotein B) were increased, but not significantly, in cancer patients compared to those with benign masses. Decreased levels of LDL-associated components were found in women with cancer recurrence by 3 years. Three apolipoproteins of high-density lipoprotein (apolipoprotein A-I, apolipoprotein A-II, apolipoprotein D) were more affected by the presence of breast masses than the lipids were. Fibrocystic disease, type of hormone binding, and recurrence within 3 years were significantly related to apolipoprotein changes, especially apolipoprotein D levels with hormone receptor binding and the apolipoprotein A-I/apolipoprotein B ratio with breast cancer recurrence.Conclusions: Prior to diagnostic biopsy, serum lipid and apolipoprotein components of low-density lipoproteins were increased in women with fibrocystic disease and early stage cancer but decreased in women with early recurrence. However, apolipoprotein A-I, apolipoprotein A-II, and apolipoprotein D, of the high-density lipoproteins, were more affected than serum lipids. The ratio of apolipoprotein A-I to apolipoprotein B serum levels at time of biopsy was the best predictor of cancer recurrence.     

Identification of the major protein components in breast secretions from women with benign and malignant breast diseases.

The protein composition of breast secretions from 99 premenopausal women with benign or malignant breast diseases and from 70 control women without breast pathologies has been studied by using polyacrylamide gel electrophoresis. These fluids have been classified into two types according to their major polypeptide components. Type I fluids are defined by three major distinctive bands at Mr 44,000, 24,000, and 17,000, while those designated Type II present distinctive bands at Mr 80,000, 15,000, and 14,000. Amino acid sequencing and immunoblotting analysis demonstrated that proteins in Type I secretions correspond to Zn-alpha 2-glycoprotein, apolipoprotein D, and gross cystic disease fluid protein-15, while those from Type II fluids have been identified as lactoferrin, lysozyme, and alpha-lactalbumin. Most women (93%) without breast pathology and most patients (88%) with benign diseases had secretions with a Type I polypeptide pattern. By contrast, a large percentage (57%) of secretions from women with breast carcinoma presented a Type II protein pattern. Further studies with a large number of women will be useful for corroborating the potential clinical interest of breast fluid protein analysis.     

Silver nucleolar organizer region assessment in tumor-cells from breast-cancer patients treated by extremely-low-frequency magnetic-field

This study assessed the value of silver staining of nucleolar organizer regions (AgNORs) in tumor cells as a potential technique for the estimation of the action of ELF magnetic field on breast cancer. The light and electron microscopy was used for analysis of tissue specimens from 4 breast cancer patients after ELF magnetotherapy and 18 untreated persons with malignant and benign breast lesions. All patients had surgical removal of neoplasms. The mean number of AgNORs and the distribution of cells according to the AgNOR number in tissue samples from patients after successful ELF magnetotherapy were closer to those of persons with benign tumors, as compared to malignant ones. The effect of ELF magnetic field at the electron microscopic level is discussed.     

Monoclonal antibody identification and characterization of a Mr 43,000 membrane glycoprotein associated with human breast cancer

A monoclonal antibody (323/A3) with a high degree of selectivity for binding to breast cancer cells was produced by immunization of mice with MCF-7 human breast cancer cells. The antigen recognized by 323/A3 on MCF-7 appears to be surface localized, and by enzyme-linked immunosorbent assay, the antibody was found to bind strongly with four of six breast cancer cell lines examined while no binding was detectable with nonbreast cancer cell lines. In vivo distribution of the 323/A3 antigen was screened by immunoperoxidase staining of formalin-fixed paraffin sections of normal human tissues and tumors. Among breast tissues, positive staining was detected with 75% (6 of 8) of metastatic lymph nodes, 59% (76 of 128) of primary breast tumors, 20% (13 of 63) of benign breast lesions, and 0% (0 of 10) of normal breast. No immunostaining was detected with a large variety and number of other normal human tissues with the exception of staining observed with epithelium of normal colon. Antigen distribution appears not to be disease specific, since positive staining was also observed with adenocarcinomas other than breast. The antigen recognized by the 323/A3 antibody was identified by Western blot analysis as a Mr 43,000 protein. The glycoprotein nature of the antigen was demonstrated by its binding to concanavalin A, specific elution with sugar, and immunoprecipitation of a Mr 43,000 radiolabeled protein from extracts of MCF-7 cells after pulse labeling with [3H]glucosamine. The 323/A3 antigen appears to be the same Mr 43,000 protein in cell lines as in breast tumors in vivo. Based on a comparison with the molecular weights of other known tumor-associated antigens and with their immunocytochemical tissue distribution, the Mr 43,000 glycoprotein described here represents a tumor-associated antigen previously undescribed in breast cancer or in other tumors. Since the Mr 43,000 glycoprotein is present on the surface of most breast cancer cells and is either absent or expressed at very low levels in most normal tissues including normal breast, the monoclonal antibody described here may have potential applications in diagnosis and management of breast cancer.     

A novel monoclonal antibody (7B10) with differential reactivity between human mammary carcinoma and normal breast

A monoclonal antibody (7B10) which displays differential reactivity with breast carcinomas compared to benign lesions or normal breast tissue was selected by fusion of spleen cells from BALB/c mice immunized with the T47D human mammary carcinoma cell line. The antigen, recognized by 7B10 on T47D cells, appeared to be both surface and cytoplasm localized, as demonstrated by indirect immunofluorescence, immunoperoxidase, and electron microscopy studies. This antibody (IgG1) bound with four human breast cancer cell lines (T47D, MCF7, ZR-75-1, and HSL53) which express estrogen receptors. No binding was observed with cancer cell lines of other origin or with normal cells. In vivo, by immunoperoxidase staining of frozen sections of normal breast, the antigen recognized by 7B10 appeared to be located on epithelial cell membranes, whereas in benign and malignant mammary disorders, staining also involved the cytoplasm, as confirmed by electron microscopy on fresh cancer tissue. On formalin-fixed, paraffin-embedded sections, cytoplasmic staining was detected in breast cancer, but no immunostaining was observed with benign lesions or normal breast. In paraffin sections, most normal tissues investigated did not react with 7B10 antibody. However, ducts in the parotid gland, tubules in the kidney and some biliary ducts, and apocrine glands in the skin showed irregular, diffuse weak staining. 7B10 was unreactive with adenocarcinomas of origin other than breast, except for some cells in ovarian clear cell carcinoma. No reactivity was observed with squamous carcinomas, lymphomas, or melanomas. The antigen recognized by 7B10 appeared to be a Mr 32,000 protein, as identified by immunoprecipitation from extracts of T47D after labeling with [35S]methionine. Since the antigen was present only on the membrane of differentiated normal mammary epithelial cells, and was also expressed in the cytoplasm of tumor cells, it may be of interest in immunological studies of mammary epithelial cell differentiation. Moreover, since in formalin-fixed tissues immunostaining is virtually confined to mammary carcinomas, monoclonal antibody 7B10 may have diagnostic applications in breast cancer.     

Benign and malignant breast disease: initial study results of serum and breast fluid analyses of endogenous estrogens

Design, methods, and study population of a long-term multidisciplinary investigation of benign and malignant breast disease were reported. This initial report focused on the relation of menstrual, reproductive, and other factors to serum and breast fluid estrogen measures [estradiol (E2), estrone (E1), percent free estrogen, and sex hormone binding globulin] among control women. After adjustment for the factors found to be related to the various estrogen measures, estrogen levels in women with benign and malignant disease were compared to those of controls. Findings were as follows: a) little evidence of any relation of most breast cancer risk factors with the various serum estrogen parameters studied; b) differences in breast fluid estrogen levels that may be relevant to the protective effect of parity on breast cancer risk; c) markedly higher levels of E2 and E1 in breast fluid than in serum and no evidence of a correlation of serum with breast fluid measures; d) no support for the hypothesis that breast cancer patients have higher serum percent free E2 than controls or women with benign breast disease; and e) higher breast fluid E2 and E1 levels in women with biopsied benign breast disease than in controls.     

Patterns of expression of keratin 19 as detected with monoclonal antibodies in human breast tissues and tumours

The monoclonal antibodies BA16 and BA17 directed to different epitopes on human keratin 19 have been tested for their reaction with normal breast and with benign and malignant breast lesions and associated tissue. In Western blots of gel-separated extracts of fibroadenomas, malignant tumours or normal mammary epithelial cells, the antibodies reacted with only one component of 40 kd molecular weight. Immunoperoxidase staining of sections of normal breast tissues showed all basal cells and a few luminal cells to be unstained by the antibodies. The distribution of the unstained (keratin 19-) luminal cells in the mammary tree is consistent with that of cells with the proliferative potential to give rise to the growth of terminal ductal lobular units (TDLU) seen at pregnancy. A total of 42 benign and 141 malignant lesions were stained with the antibodies, and a clear difference in staining pattern was seen between the benign and malignant tumours. All but 3 of the benign lesions showed a heterogeneous staining pattern with 5-50% unstained cells. In contrast, the cancer cells in 106/116 invasive primary tumours and in all 21 metastatic lesions examined showed a homogeneously positive reaction with antibodies BA16 and BA17: the malignant cells in 4 cases of Paget's disease also showed homogeneously positive staining with the antibody. In the malignant tumours, the observed homogeneity in expression of keratin 19 was confined to the malignant cells; tumour-associated normal tissue and benign proliferative lesions contained keratin 19-cells. Seven pure in situ tumours were examined and 5 showed the homogeneous pattern of staining characteristic of invasive tumours while 2 contained a high number of keratin 19-cells. A general model is presented to explain the presence of keratin 19-cells in benign proliferation and the dominance of keratin 19-cells in invasive carcinoma.     

The presence of soluble c-erbB-2 in saliva and serum among women with breast carcinoma: a preliminary study.

The protein c-erbB-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsies from women diagnosed with malignant tumors. Present studies suggest that soluble fragments of the c-erbB-2 oncogene may be released from the cell surface and become detectable in patients with carcinoma of the breast. Consequently, the purpose of this study was to assay the c-erbB-2 protein in the saliva and serum of women with and without carcinoma of the breast and to determine whether the protein possesses any diagnostic value. To determine the diagnostic utility of this oncogene, the soluble form of the c-erbB-2 protein was assayed in the saliva and serum using ELISA in three different groups of women. The three groups consisted of 57 healthy women, 41 women with benign breast lesions, and 30 women diagnosed with breast cancer. To compare the relative diagnostic utility of the c-erbB-2 protein, CA 15-3 was also measured. The CA 15-3 measurements served as a "gold standard" by which to compare the c-erbB-2 protein's diagnostic effectiveness. We found c-erbB-2 protein in the saliva and serum of all three groups of women. The salivary and serological levels of c-erbB-2 in the cancer patients, however, were significantly higher (P < 0.001) than the salivary and serum levels of healthy controls and benign tumor patients. Additionally, the c-erbB-2 protein was found to be equal to or to surpass the ability of CA 15-3 to detect patients with carcinoma. The results of the pilot study suggest that the c-erbB-2 protein may have potential use in the initial detection and/or follow-up screening for the recurrence of breast cancer in women.