The ABO(H) cell surface antigens in carcinoma and benign lesions of the breast

The ABO(H) cell surface antigens of 13 breast carcinomas and 17 benign breast lesions were tested with a specific red cell adherence assay (SRCA). All 13 breat carcinomas, including 2 lobular carcinomas in situ and 1 noninfiltrating ductal carcinoma, had lost their ABO(H) surface antigens. Fourteen of 17 benign breast lesions had retained their ABO(H) surface antigens. The benign lesions losing their antigens were 1 case each of atypical intraductal hyperplasia, sclerosing adenosis, and intraductal papilloma. SRCA may be a predictor of which benign breast lesions are in fact premalignant.     

A,B and H isoantigens in oral lesions

Expression of blood group A, B and H iso-antigens in oral mucosae was demonstrated by specific red cell adherence test in forty seven mucosal biopsies from oral cavity (14 normal, 10 leucoplakia and 23 squamous cell carcinomas). All normal mucosae gave a positive reaction whereas in malignancy only 6 cases of well differentiated squamous cell carcinomas were either weekly positive or showed a patchy reaction. Remaining cases were negative irrespective of their grading. In leucoplakia though the test was positive in all the cases, the intensity of adherence was less as compared to normal mucosa. The intensity of adherence was found to be directly related to the degree of cellular differentiation. Study of A, B and H isoantigens might help in deciding the prognosis in leukoplakia and/or early detection of malignancy.     

Expression of A and B tissue isoantigens in benign and malignant lesions of the breast

AB isoantigens are widely distributed in human tissues and loss of AB isoantigen expression has been shown to be an early marker for carcinomatous transformation in some tissues. We therefore applied the Specific Red Cell Adherence Reaction (SRCA) for detection and localization of AB isoantigens in tissue to the study of benign and malignant proliferative lesions of the breast. Twenty-nine lesions in 19 patients were studied. AB isoantigen expression in normal breast tissue was found to be largely confined to the mammary duct system. Loss of AB isoantigen expression was a consistent feature of intraductal carcinoma (3 of 3 cases). Proliferative lesions associated with fibrocystic disease also demonstrated varying degrees of isoantigen loss (simple cystic disease, 3 of 8 cases; intraductal hyperplasia, 6 of 7 cases; sclerosing adenosis, 4 of 4 cases; and intraductal papillomatosis, 7 of 7 cases negative for isoantigen). In contrast to other systems, loss of AB isoantigen expression in the breast appears to be a consistent marker of apparently benign proliferative duct lesions associated with fibrocystic disease, as well as duct carcinoma. The early loss of AB isoantigen expression in these histologically benign lesions supports a possible link between fibrocystic disease and mammary carcinoma. In contrast to other tissues, loss of AB isoantigen expression in proliferative breast lesions is not necessarily evidence of malignancy.     

Cytomorphometric differentiation of intraductal proliferative breast lesions

BACKGROUND: Although cytologic examination has been an indispensable procedure for the diagnosis of various breast diseases, it is often difficult to make a precise diagnosis of intraductal proliferative breast lesions preoperatively. The present study attempts to clarify the differentiation of the lesions by the cytologic morphometric approach. METHODS: Cytologic specimens from 21 intraductal lesions, including nine ductal carcinomas in situ (DCIS), seven ductal hyperplasias (DH), and five papillomas were evaluated. Using a microscope connected to a computerized video system, the mean nuclear area, the perimeter, the form factor, the largest to smallest diameter ratio of the nuclei (LS ratio), and the coefficient of variation of the nuclear area (NACV) were measured and analyzed. RESULTS: The mean nuclear area and perimeter were significantly higher in the cases of DCIS than in DH (p < 0.01) and papilloma (p < 0.005). Similarly, DCIS had higher NACV values than the other groups (p < 0.05 and p < 0.005, respectively). There were no significant differences in form factor or LS ratio. CONCLUSIONS: The quantitative estimation of cytologic nuclear features is useful for preoperative differential diagnosis of intraductal proliferative lesions of the breast.     

ABO (H) cell surface antigens in benign and malignant parotid neoplasms

Twenty-two inflammatory, benign, or malignant parotid lesions were studied by means of the specific red cell adherence test (SRCA), a modification of the Coombs' mixed cell agglutination reaction. In 22 normal parotid tissues the acinar structures were devoid of red cell agglutination, but it was present in ductal epithelium. Findings were similar in 2 cases of parotitis, 11 benign mixed tumors, and 1 malignant mixed tumor. All lacked red cell agglutination in areas of neoplastic change. Benign Warthin's tumors (4 cases) demonstrated antigenicity in the columnar epithelial component of the tumor, but lacked red cell agglutination in areas of the lymphoid component. One malignant Warthin's tumor showed agglutination in areas of normal columnar epithelium but not in areas of malignant dedifferentiation. Undifferentiated carcinoma (1 case) and adenoid cystic carcinoma (2 cases) did not possess detectable ABO (H) antigens in neoplastic areas of the gland. The absence of ABO antigens in normal acinar glands supports their suggested myoepithelial or mesenchymal derivation, as the absence of antigen in benign and malignant mixed tumors supports their proposed mesenchymal derivation. Ductular epithelium and the epithelial components of benign Warthin's tumors have ABO (H) antigens, while the loss of antigen in the epithelial portion of the malignant Warthin's tumor is characteristic of epithelial neoplastic dedifferentiation. Loss of antigen in adenoid cystic and undifferentiated carcinomas of the parotid supports the concept that antigen is absent in epithelially derived malignant neoplasms.     

细胞DNA倍体分析评估宫颈上皮内瘤变

目的评价通过细胞DNA倍体分析诊断宫颈上皮内瘤变（CIN）的效果。方法对87例宫颈癌普查妇女用宫颈刷取材、液基薄层制片,由细胞学医师对巴氏染色片做常规细胞诊断,应用全自动DNA倍体分析仪对DNA染色片进行自动扫描诊断。对活检样本做出病理诊断,并应用免疫组化ABC法测定宫颈鳞状上皮细胞核内Ki67蛋白的表达。结果87例受检者中,常规细胞学诊断为正常30例,非典型鳞状细胞（ASCUS）20例,低度鳞状上皮内病变（LSIL）30例,高度鳞状上皮内病变（HSIL）7例;无异倍体细胞者26例,有异倍体细胞者61例,其中Ⅰ级17例,Ⅱ级21例,Ⅲ级23例。20例ASCUS者中,有7例无异倍体细胞,未发现一例CIN2以上级别的病理改变,Ki67阳性细胞分布在鳞状上皮下方37．1％范围内;13例有异倍体细胞者中,11例有CIN2以上病理改变,Ki67免疫阳性细胞分布于上皮层下46．2％范围内。30例LSIL者中,有7例未发现异倍体细胞,其中3例有CIN2以上病理改变,Ki67阳性细胞只分布在鳞状上皮下方37．1％范围内;23例伴有DNA异倍体细胞者中,22例发现CIN2以上病理改变,Ki67阳性细胞增至鳞状上皮层中上方62．6％范围内,与7例未发现异倍体细胞者差异有统计学意义（P〈0．01）。7例HSIL病例中均有DNA异倍体细胞出现。以≥3个DNA异倍体细胞作为评估CIN2及以上病理改变的标准,其敏感性为72．7％,特异性为87．5％,阳性预测值为90．9％,阴性预测值为65．1％,均比以常规细胞学诊断为LSIL及以上级别作为评估CIN2及以上病理改变的标准（分别为58．2％、84．4％、86．5％和54．0％）要高。结论DNA倍体分析可诊断宫颈CIN病变,并预测其发展。     

Detection of ABO(H) blood group antigens: a study in tissue culture

The association between malignant transformation and the loss of ABO(H) blood group antigens was documented by several authors. Most of the work was done on paraffin sections, though a small portion was performed on fresh frozen tissues. We suggest that the specific red cell adherance (SRCA) test can be applied to tissues cultivated in tissue culture for determination of malignant transformation. This study supports this assumption.     

Assessment of intratumoral vascularization (angiogenesis) in breast cancer prognosis

The search for prognostic markers is important both to identify those patients with occult metastases and also to spare chemotherapy in those patients whose tumors have not developed the capacity for distant spread. Angiogenesis, the formation of new blood vessels, is necessary for breast cancer growth and metastasis. Good correlation has been demonstrated between intratumoral vascularization and outcome in patients with breast cancer. Intratumoral vascularization in human breast cancer can be measured by using standard immunohistochemical methods. Strict guidelines for scoring need to be followed. Although attempts are being made to automate the reading, visual scoring remains superior. We studied a population of women with small node-negative breast cancer who received no adjuvant therapy and have a median follow-up of 15 years. We have found intratumoral vascularization, as measured by microvessel count, to be an independent prognostic factor for disease-free survival. Low microvessel count identifies a group of patients with a 20 year disease free survival of 93%. The proportion of women with low microvessel count decreases with increase in tumor size and increases with patient age. But even in mammographically detected nonpalpable breast cancer, that is, the smallest breast cancer we currently detect, the majority already have high microvessel count. Intratumoral vascularization appears to be an early event that is necessary but not sufficient for metastatic progression. Microvessel count seems to be an excellent marker to identify patients with good prognosis because those with low microvessel count have a 93% disease-free survival irrespective of size, grade, or estrogen receptor status, but is less good at predicting those at high risk since the 20-year disease-free survival is still 67-70% in those with high microvessel count. Thus, the higher risk group needs to be further stratified using additional prognostic factors.     

Antibody dependent cellular phagocytosis (ADCP) and antibody dependent cellular cytotoxicity (ADCC) of breast cancer cells mediated by bispecific antibody, MDX-210

Background: MDX-210 is a bispecific antibody (BsAb) with specificity for both the proto-oncogene product of HER-2/neu (c-erbB-2) and FcRI (CD64). HER-2/neu is overexpressed in malignant tissue of approximately 30% of patients with breast cancer, and FcRI is expressed on human monocytes, macrophages, and IFN- activated granulocytes. We investigated phagocytosis and cytolysis of cultured human breast cancer cells by human monocyte-derived macrophages (MDM) mediated by BsAb MDX-210, its partially humanized derivative (MDX-H210), and its parent MoAb 520C9 (anti-HER-2/neu) under various conditions.Materials and Methods: Purified monocytes were cultured with GM-CSF, M-CSF, or no cytokine for five or six days. Antibody dependent cellular phagocytosis (ADCP) and cytolysis (ADCC) assays were performed with the MDM and HER-2/neu positive target cells (SK-BR-3). ADCP was measured by two-color fluorescence flow cytometry using PKH2 (green fluorescent dye) and phycoerythrin-conjugated (red) monoclonal antibodies (MoAb) against human CD14 and CD11b. ADCC was measured with a non-radioactive LDH detection kit.Results: Both BsAb MDX-210 (via FcRI) and MoAb 520C9 (mouse IgG1, via FcRII) mediated similar levels of ADCP and ADCC. ADCP mediated by BsAb MDX-H210 was identical to that mediated by BsAb MDX-210. Confocal microscopy demonstrated that dual-labeled cells represented true phagocytosis. Both ADCP and ADCC were higher when MDM were pre-incubated with GM-CSF than when incubated with M-CSF.Conclusions: BsAb MDX-210 is as active in vitro as the parent MoAb 520C9 in inducing both phagocytosis and cytolysis of MDM. MDX-210 and its partially humanized derivative, MDX-H210, mediated similar levels of ADCP. GM-CSF appears to superior to M-CSF in inducing MDM-mediated ADCC and ADCP. These studies support the ongoing clinical investigations of BsAb MDX-210 and its partially humanized derivative.     

Assessment of soft tissue lesions suspicious for liposarcoma by F18-deoxyglucose (FDG) positron emission tomography (PET)

BACKGROUND: F18-deoxyglucose (FDG) positron emission tomography (PET) is a promising imaging technique. The aim of this study was to investigate the use of FDG PET in patients with suspected liposarcomas (LS). PATIENTS AND METHODS: Forty-two masses were studied. The FDG uptake was estimated in tumor (T) and normal tissue (NT). The data were analyzed with respect to pathological findings. RESULTS: Pathology revealed 11 primary LS, 14 locally recurrent LS, 5 other sarcomas, 1 inflammation, 1 lymphoma and 10 benign lesions. FDG uptake (T-to-NT ratio) in 25 LS corresponded with the histological subtype. Pleomorphic, mixed and myxoid LS showed an increased T-to-NT ratio and were thus visualized. Four out of six well-differentiated LS presented a low FDG uptake. Like subtype, the tumor grade also corresponded to FDG uptake. The T-to-NT ratio of higher grade LS, contrary to low grade LS, was uniformly increased. Primary LS were distinguishable from benign tumors, while other sarcomas, inflammation and lymphoma were not. Recurrence was detected with a sensitivity of 86% and a specificity of 100%. False-negative diagnoses occurred only in well-differentiated recurrences. CONCLUSION: FDG uptake in LS correlates with the histological subtype and tumor grade. The diagnostic value of FDG PET in LS, therefore, is influenced by histomorphological parameters. Our data suggest that pleomorphic, mixed and higher-grade LS recurrences are preferentially amenable to FDG PET imaging.