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A Thor

Publications and source records attributed to A Thor.

At least 55 records · Page 3Linked to original sources

Immunological characterization of a novel human colon-associated antigen (CAA) by a monoclonal antibody.

We have generated a monoclonal antibody (MAb), designated anti-CAA (colon-associated antigen), using as immunogen a membrane-enriched fraction of a biopsy from a moderately-differentiated human colonic adenocarcinoma. The molecular weight of this reactive antigen was determined by Western blotting to be greater than 200 kDa. When immunohistochemical techniques were used, MAb anti-CAA reacted with epithelium in the majority of normal, dysplastic and malignant colon specimens tested (greater reactivity was observed in normal colon than in benign or malignant lesions). Cell sorter analyses demonstrated a heterogeneous distribution of CAA on the cell surface of the well-differentiated LS-174T cell line. Antigen positive and antigen-negative cells were separated by means of flow cytometric techniques. These two subpopulations were then inoculated into immunosuppressed rats, resulting in xenograft tumors which differed significantly in their degree of histologic differentiation. Antigen-positive cells developed into well-differentiated adenocarcinomas, while antigen-negative cells developed into poorly differentiated adenocarcinomas. These results, along with immunohistochemical studies, indicate that the antigen detected by MAb anti-CAA has characteristics of a colon-associated antigen whose expression correlates with cellular differentiation. Moreover, differences in molecular weight as well as tissue distribution indicate that CAA may be a novel antigen different from those previously described.

Adenocarcinoma↗

Quantitative and qualitative aspects of radiolocalization in colon cancer patients of intravenously administered MAb B72.3.

Monoclonal antibody (MAb) B72.3 has been previously shown, by in vitro assays, to have a high degree of specificity for carcinomas of the colon, ovary and breast versus normal adult tissues. B72.3 IgG was labelled with 131I and injected i.v. into 20 patients with known or suspected colorectal cancer. All patients subsequently underwent surgical exploration, with tumor and selected normal tissues removed for staging purposes. The selective localization of 131I-MAb B72.3 IgG was demonstrated in biodistribution studies in which the % ID/g of each tumor was compared with that of the normal tissues, thus providing a relative RI for each lesion. Of the tumor lesions, 70% (99/142) had an RI of at least 3 (i.e., 3 times greater uptake per gram than normal tissues), and 31% of the tumor lesions had RIs of over 10. Only 12 of 210 (6%) histologically normal tissues had RIs of greater than 3; either these tissues were adjacent to or draining tumor masses or, as in the case of 2 patients, the high RI values were apparently due to deposition of immune complexes in the splenic tissues. Several parameters were studied to determine factors that might influence MAb localization. Whereas tumors of all histologic types localized the MAb, 31% of the well-differentiated mucinous carcinomas displayed tumor-to-normal ratios greater than 10, while less than 5% of the lesions of other tumor types demonstrated similar localization. The expression of the antigen (TAG-72) detected by MAb B72.3 in these tumors, as studied by immunohistochemical techniques using tissue sections, did not always correlate with the outcome of the MAb distribution. No differences in MAb uptake were observed among the carcinoma lesions from numerous anatomic locations, demonstrating the ability of i.v. administered B72.3 to reach all the tumor sites. Furthermore, autoradiographic studies of tumors showed good penetration of the MAb into the medial areas of the tumors, regardless of their size.

Adolescent↗

Adjunct to the diagnostic distinction between adenocarcinomas of the ovary and the colon utilizing a monoclonal antibody (COL-4) with restricted carcinoembryonic antigen reactivity.

Malignant ovarian tumors may represent either primary ovarian cancers or metastatic lesions (from patients with demonstrated primary cancers at other body sites) whose distinction may be difficult using clinical, surgical, and pathological criteria. Monoclonal antibody (MAb) COL-4, reactive with carcinoembryonic antigen, has previously been shown to react preferentially with adenocarcinomas of the colon versus a variety of normal tissues. We report here that MAb COL-4 is strongly reactive with primary colonic carcinomas (N = 50), as well as regional (N = 42), and distant (N = 20) metastases of colonic adenocarcinoma. In contrast, MAb COL-4 demonstrated little to no reactivity with primary (N = 53) and metastatic carcinomas of the ovary (N = 23) including serous, mucinous, and poorly differentiated adenocarcinomas using immunohistochemical techniques. This differential reactivity was statistically significant (P less than 0.001), suggesting the potential clinical utility of MAb COL-4 in the differentiation of ovarian from colonic adenocarcinoma. Solid-phase quantitative radioimmunoassays and Western blotting techniques confirmed these results. Data are also presented that the carcinoembryonic antigen molecules or epitopes recognized by a more classical broadly reactive anti-carcinoembryonic antigen MAb are distinct from those recognized by MAb COL-4. Other carcinomas which also metastasize to the ovary and may be confused clinically with a primary ovarian tumor such as adenocarcinomas of the stomach and breast were also evaluated for reactivity with MAb COL-4. COL-4 was also reactive with all gastric carcinomas evaluated, but failed to react with breast carcinomas. Hence, COL-4 can now be utilized as an immunohistochemical adjunct for the differentiation of ovarian from gastrointestinal adenocarcinoma which can be difficult to distinguish by clinical, surgical, and histological parameters.

Adenocarcinoma↗

Immunohistochemical evaluation of ras oncogene expression in pulmonary and pleural neoplasms.

We undertook an immunohistochemical analysis of human bronchopulmonary epithelial neoplasms and pleural mesotheliomas using a monoclonal antibody which recognizes ras oncogene products (p21ras). The monoclonal antibody, RAP-5, recognizes both unaltered and certain mutated p21ras. Formalin fixed and paraffin embedded tissue samples of 187 lung epithelial tumors and 27 pleural mesotheliomas were investigated; normal and bronchiectatic lungs were similarly studied. Normal lung and pleural tissue did not immunostain except for occasional type II pneumocytes. Reactive type II pneumocytes adjacent to carcinomas and bronchiectasis immunostained consistently. Twenty four/34 (71%) squamous carcinomas immunostained. Only 8/50 (16%) adenocarcinomas immunostained focally and weakly whereas 19/24 (79%) bronchioloalveolar carcinomas immunostained. Eleven/18 (61%) large cell carcinomas immunostained with variable intensity. Eleven/13 (85%) carcinoids, 6/7 (85%) well differentiated neuroendocrine carcinomas, and 18/21 (86%) intermediate cell neuroendocrine carcinomas immunostained while none of 20 small cell neuroendocrine carcinomas immunostained. Only a few mesotheliomas were immunostained focally. Two/14 (14%) epithelial type and 1/9 (11%) biphasic type mesotheliomas immunostained weakly; none of 4 spindle cell mesotheliomas immunostained. We conclude that while at least occasional cases of most types of pulmonary epithelial neoplasms express p21ras, the frequency and intensity of the expression are distinctly greater in certain tumor types such as squamous, bronchioloalveolar, and neuroendocrine neoplasm except for the small cell type. Contrary to these lung epithelial neoplasms, most mesotheliomas did not immunostain for p21ras. Whether the enhanced p21ras expression may point to a different mechanism of transformation or may merely reflect differentiation features remains undetermined.

Histocytochemistry↗

Monoclonal antibody B72.3 reactivity with human endometrium: a study of normal and malignant tissues.

Monoclonal antibody (MAb) B72.3, reactive with a high molecular weight mucin-like glycoprotein [termed tumor-associated glycoprotein (TAG)-72], has been shown previously to react preferentially with adenocarcinomas of the ovary, breast, and colon versus a variety of normal human tissues using immunohistochemical and radioimmunoassay (RIA) techniques. We report here B72.3 reactivity with normal postovulatory endometria, in contrast to proliferative phase epithelia that were nonreactive. Both immunohistochemical and RIA techniques were used to evaluate this phenomenon. TAG-72 expression was also detected in 100% of endometrial adenocarcinomas (n = 32) examined. No MAb B72.3 reactivity was noted in resting, postmenopausal endometria; however, it was present in hyperplastic lesions and appeared to correlate with the severity of histologic abnormality. The utility of MAb B72.3 for screening, radiolocalization, or perhaps therapy of endometrial adenocarcinoma is also discussed.

Adenocarcinoma↗

Applications of immunocytochemistry to clinical cytology.

This article reviews the recent studies reporting the applications of immunocytochemistry to diagnostic problems in clinical cytology. A series of studies with monoclonal antibody (MAb) B72.3 is discussed in detail. MAb B72.3, reactive with a high molecular weight, glycoprotein, tumor-associated antigen, designated TAG-72, has been shown previously to be reactive with formalin-fixed, paraffin-embedded tissue sections of adenocarcinomas of the ovary, colon, and breast, but not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct to diagnose carcinoma in cell block and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. Using the avidin-biotin complex (ABC) method of immunoperoxidase staining and formalin-fixed, paraffin-embedded cell suspensions, MAb B72.3 detected tumor cells in effusions from the majority of patients with adenocarcinoma of the breast. No reactivity was demonstrated in any cell type in benign effusions. In contrast, MAb B72.3 showed no reactivity to leukemic or lymphomatous effusions, or to mesothelial cells from malignant effusions. MAb B72.3 also detected tumor cells in effusion specimens from most of the patients with "non-small cell" carcinoma of the lung and with carcinoma of the ovary. MAb B72.3 was also used with fine-needle aspiration biopsies (FNABs) and corresponding surgically excised tumors to determine cellular reactivity. Positive staining with MAb B72.3 was observed in needle aspirates of the great majority of "non-small cell" carcinomas of the lung, adenocarcinomas of the breast, adenocarcinomas of the colon, and carcinomas from other body sites. In contrast, small cell carcinomas of the lung, malignant melanomas, lymphomas, sarcomas, and glial tumors stained negatively with the antibody. Most benign lesions from the breast, lung, pancreas, parotid, and thyroid also showed no staining. In many patients, tumor-bearing tissue had also been resected and was available for comparative examination with MAb B723. In more than 90% of these patients, the staining patterns of tumor cells in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tumors. From these studies it is concluded that MAb B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells versus benign cells, is most selectively expressed in carcinomas, and may be used as a novel adjunct for the diagnosis of neoplasms in effusions and in FNABs.

Animals↗

Modulation of human tumor antigen expression.

With membrane-enriched fractions prepared from human metastatic breast tissue used as immunogen, a group of monoclonal antibodies (MAbs) were generated that recognized several distinct antigens on breast and other carcinomas. The antibodies were found to react with established human tumor cells in culture as well as in immunohistochemical protocols using sections of primary and metastatic lesions. One MAb, B72.3, demonstrated a high degree of selective reactivity for human carcinomas in that no reactivity was found with a large number of different normal tissues. These MAbs were used to demonstrate the heterogeneity of expression of the tumor antigens as well as the intrinsic cellular factors (i.e., cell-cycle kinetics and clonal variability) that modulate their expression. Additional studies showed that recombinant human leukocyte interferon can act as a potent regulator of surface antigen expression on human carcinoma cells. Analysis of these cells by radioimmunoassay or flow cytometry revealed that interferon treatment resulted in a higher percentage of the cell population that bind the MAb to the surface antigen. Furthermore, interferon treatment also increases the level of expression for particular tumor antigen throughout the tumor cell population. Experimental models were also developed to investigate the active localization of a radiolabeled MAb by a human tumor xenograft in athymic mice. The results demonstrate active uptake of an 125I-B6.2 by a transplantable human breast tumor that expressed significant quantities of the B6.2-reactive 90 kD tumor antigen. In contrast, a human melanoma cell line grown as a solid, subcutaneous tumor in athymic mice did not localize the labeled B6.2 and does not express the associated 90 kD antigen. We report the generation and characterization of anti-breast carcinoma MAbs. These immunologic probes were used to study relevant breast tumor antigens, the factors that influence their level of expression, and the ability of human tumors grown in athymic mice to localize radiolabeled antibodies.

Animals↗

Expression of ras oncogene p21 antigen in normal and proliferative thyroid tissues.

The ras oncogene p21 antigen (p21) has been identified in several epithelial malignancies, including breast, colon, bladder, and prostate. The pattern and intensity of immunoreactivity between normal and neoplastic tissues has been distinctly different. The authors examined thyroid lesions from 73 different cases by immunohistochemistry for the expression of p21 with a monoclonal antibody (RAP-5). Normal thyroid tissues (4) showed the least immunoreactivity, while papillary carcinomas (8), Hurthle cell carcinomas (10), and follicular carcinomas as (3) showed slightly more intense staining than Hurthle cell adenomas (12) or follicular adenomas (9). Anaplastic carcinomas (4) showed much less intense staining than most other carcinomas, while medullary thyroid carcinomas (5) showed only slight immunoreactivity. Inflammatory thyroid lesions associated with goiters, including Hashimoto's thyroiditis (6) and Graves' disease (8), showed moderate to intense expression of p21 as did multinodular goiters (4). Semiquantitative analysis of staining intensity by serial dilution of the primary antibody showed significant differences in staining between normal thyroid and some carcinomas (P less than 0.05), but not between carcinomas and adenomas. These results show that while antibody RAP-5 detects an antigen that is only weakly expressed in normal thyroids, this antigen is more strongly expressed in benign and malignant thyroid tumors, as well as in inflammatory and nonneoplastic proliferative thyroid lesions. It is thus not helpful in identifying differences between neoplastic and non-neoplastic thyroid lesions.

Adenoma↗

Quantitation of Harvey ras p21 enhanced expression in human breast and colon carcinomas.

Molecular studies have demonstrated increased expression of the Harvey (Ha) ras oncogene in human breast and colon carcinomas. With the use of a direct-binding liquid competition radioimmunoassay (RIA), capable of providing truly quantitative analysis of the 21,000-dalton (p21) ras oncogene and protooncogene products, absolute levels of Ha-ras p21 have been determined in human breast and colon carcinomas, benign lesions, and/or their respective normal tissues. Enhanced Ha-ras expression was documented in 66% of breast and 100% of colon carcinomas as compared with their normal counterparts, with levels in breast carcinomas ranging from 10.1 to 50.4 pg ras p21/micrograms protein and those in colon carcinomas ranging from 18.4 to 51.7 pg ras p21/micrograms protein. Some dysplastic lesions of the breast and colon also contained elevated Ha-ras p21. Relative levels of Ha-ras p21 expression, detected by competition RIA, correlated with percent Ha-ras p21-positive cells as determined by immunohistochemical assays. By use of liquid competition RIA and immunohistochemical assays, it has been shown that levels of ras p21 expression did not always correlate between primary and metastatic colon lesions of the same patient. The use of the quantitative RIA and semiquantitative immunohistochemical assays, in concert with cDNA probes for identification of specific ras point-mutated oncogenes or protooncogenes, may now provide the means for definitive quantitative analyses of ras p21 in human carcinomas and benign lesions.

Adenocarcinoma↗

Tumor-associated glycoprotein (TAG-72) detected in adenocarcinomas and benign lesions of the stomach.

Murine monoclonal antibody (MAb) B72.3, prepared against a membrane-enriched extract of metastatic carcinoma and reactive with a high-molecular-weight determinant, designated tumor-associated glycoprotein (TAG)-72, was shown to be reactive immunohistochemically with 97% of a variety of primary adenocarcinomas of the stomach (n = 40). All "early" gastric carcinomas were reactive with MAb B72.3, although the average percentage cellular reactivity was lower than in "advanced" carcinomas. TAG-72 antigen was detected in benign lesions (i.e. adenomatous polyps and hyperplastic polyps) with intestinal metaplasia. Dysplastic lesions characterized by cellular atypia, abnormal differentiation, and disorganized mucosal architecture demonstrated higher TAG-72 expression than non-dysplastic epithelia. In contrast, normal gastric mucosa was generally non-reactive with MAb B72.3. Assays using serial sections of normal, benign and malignant gastric tissues with two MAbs (B1.1 and COL-6) directed against distinct epitopes of carcinoembryonic antigen (CEA) demonstrated differential reactivity, confirming that TAG-72 and CEA are distinct, non-coordinately expressed antigens. Our results suggest that TAG-72 antigen may be expressed in malignant and dysplastic epithelial cells, as well as in intestinalized epithelium of the stomach which has been closely related to subsequent carcinoma development. Hence, MAb B72.3 may be a useful immunohistochemical adjunct for detecting early foci of adenocarcinomas and premalignant lesions of the stomach.

Adenocarcinoma↗

Expression of ras oncogene p21 in prostate cancer.

The major neoplastic transformation-inducing genes of human solid tumors are members of the ras oncogene family. We used an immunohistochemical assay to assess expression of both the unaltered and the mutated ras oncogene protein (p21) in normal and neoplastic prostatic cells. With the concentration of monoclonal antibody used in this study, epithelial and stromal cells from subjects with normal prostates and from 19 patients with benign prostatic hyperplasia were negative for p21 antigen. This antigen was detected in 2 of 6 prostates with Grade I carcinoma, 4 of 6 with Grade II, and all of 17 with higher grades. A semiquantitative immunohistochemical method demonstrated that expression of the p21 antigen in a carcinoma strongly correlated with nuclear anaplasia and was inversely related to the degree of glandular differentiation. However, markedly anaplastic tumors were often more heterogeneous in expression of p21 and contained areas of low staining for the antigen. Comparison of p21 antigen with tumor carcinoembryonic antigen and prostate-specific antigen demonstrated that ras p21 was the only phenotypic marker that correlated with histologic tumor grade. Thus, ras oncogene p21 may represent a new class of biologically relevant tumor markers and may be a useful adjunct to histopathologic examination in determining the prognosis of patients with prostate cancer.

Antigens, Neoplasm↗

Use of a monoclonal antibody (B72.3) as a novel immunohistochemical adjunct for the diagnosis of carcinomas in fine needle aspiration biopsy specimens.

Monoclonal antibody B72.3 has been shown to be reactive with a high-molecular-weight glycoprotein complex termed TAG(tumor-associated glycoprotein)-72. By the avidin-biotin immunoperoxidase method, fine needle aspirates and corresponding surgically excised tumor tissues from both malignant and benign tissues were analyzed for TAG-72 expression. Staining (range, 1 to 100 per cent of tumor cells) with monoclonal antibody B72.3 was observed in needle aspirates from 18 of 18 adenocarcinomas and adenosquamous carcinomas of the lung, 17 of 21 adenocarcinomas of the breast, and six of six adenocarcinomas of the colon, as well as adenocarcinomas from other body sites. In contrast, small cell carcinomas of the lung, malignant melanomas, lymphomas, and sarcomas did not stain with the antibody. Benign lesions from the breast, lung, pancreas, parotid, and thyroid also failed to stain. In 66 patients, tumor-bearing tissue had also been resected and was available for comparative examination with monoclonal antibody B72.3. In 62 of these 66 patients, the staining patterns in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tissues. From these studies it is concluded that monoclonal antibody B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells but not in benign cells and is most selectively expressed in adenocarcinomas. This monoclonal antibody may be used as a novel adjunct for the diagnosis of carcinoma in fine needle aspiration biopsy specimens.

Antibodies, Monoclonal↗

Identification of adenocarcinoma in cytospin preparations of effusions using monoclonal antibody B72.3.

Metastatic adenocarcinoma in human effusions can be difficult to distinguish from reactive mesothelial cells, particularly if the malignant cells are rare, have bland cytologic features, or occur as single cells rather than clusters of cells. Monoclonal antibody (MAb) B72.3, generated against a membrane-enriched fraction of breast carcinoma, has been shown to be reactive with formalin-fixed, paraffin-embedded tissue sections of human breast and colon carcinomas but not with sarcomas, melanomas, hematopoietic neoplasms, or a variety of normal adult tissues. The authors have adapted the avidin-biotin-immunoperoxidase method using MAb B72.3 to evaluate cytospin preparations of pleural and peritoneal effusions for the presence of adenocarcinoma cells. The cytospin method was selected because it provides a rapid, efficient, and inexpensive means of evaluating effusions for cellular content. Reactive effusions from patients with no history of adenocarcinoma as well as obviously malignant effusions from patients with documented adenocarcinoma were studied. MAb B72.3 demonstrated no reactivity with any of the variety of cell types in the reactive specimens from patients without a history of adenocarcinoma. In contrast, in all of the malignant effusions studied, 10-90% of the nonhematopoietic cells demonstrated reactivity with MAb B72.3. In addition, MAb B72.3 highlighted occult adenocarcinoma cells in cytospin preparations of effusion fluids from patients with a primary diagnosis of adenocarcinoma in which no definite malignant cells could be identified using standard cytologic criteria.

Adenocarcinoma↗

Phenotypic heterogeneity of a tumor-associated antigen in adenocarcinomas of the colon and their metastases as demonstrated by monoclonal antibody B72.3.

To determine the potential antigenic heterogeneity which might exist between a primary colon carcinoma lesion and its metastases, we stained the formalin and Zenker's fixed paraffin-embedded tissues from the resection specimens of 12 patients with Duke's Stage C adenocarcinoma of the colon with monoclonal antibody (MAb) B72.3. This MAb previously has been shown to react with a high molecular weight tumor-associated glycoprotein (termed TAG-72), which is selectively expressed in adenocarcinomas versus normal adult tissue. Five to 90% of malignant cells from all primary lesions stained with MAb B72.3 in paraffin-embedded tissue. A significantly diminished percentage of cells stained from the metastases in lymph nodes and distant sites. Pearson correlation coefficients showed that the antigenic expression of the metastasis in the lymph node was a better indicator of the antigenic expression of the metastasis in the distal site than was the primary lesion in the colon. These findings suggest that the effective use of monoclonal antibodies for diagnostic imaging or therapeutic purposes may require the evaluation of the antigenic expression in regional node metastases rather than that of the primary lesion.

Adenocarcinoma↗

The diagnostic distinction between malignant mesothelioma of the pleura and adenocarcinoma of the lung as defined by a monoclonal antibody (B72.3).

The correct distinction between malignant mesothelioma of the pleura and adenocarcinoma of the lung has become increasingly complex, with a variety of histochemical, immunohistochemical, and ultrastructural studies to be performed on biopsy material. The reliability of immunohistochemical studies has been hampered by the use of polyclonal antisera to "carcinoembryonic antigen (CEA)" and keratin. Hybridoma technology now offers monoclonal antibodies (MAbs) in unlimited quantity and standardized quality to selective ranges of specific antigenic determinants. MAb B72.3, generated against a membrane-enriched fraction of human metastatic breast carcinoma, was used to distinguish malignant mesothelioma of the pleura from adenocarcinoma of the lung in tissue sections and was compared in terms of diagnostic utility with polyclonal anti-keratin and anti-CEA to make the same distinction. Reactivity with MAb B72.3 in at least 10% of tumor cells or more was noted in 19 of 22 adenocarcinomas of the lung (P greater than 0.0001), whereas none of the 20 cases of malignant mesothelioma demonstrated comparable reactivity. Furthermore, MAb B72.3 showed no reactivity with benign mesothelial proliferations. MAb B72.3 thus appears to be an appropriate diagnostic adjunct capable of discriminating between these malignancies.

Adenocarcinoma↗

Phenotypic characterization of lung cancers in fine needle aspiration biopsies using monoclonal antibody B72.3.

Monoclonal antibody B72.3, reactive with a high-molecular-weight glycoprotein tumor-associated antigen (designated TAG-72), has been previously shown to be reactive with formalin-fixed paraffin-embedded tissue sections of adenocarcinomas of the ovary, colon, and breast and not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct to diagnose carcinoma in cell block and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. In this study, fine needle aspiration biopsies of 127 lung cancers (93 primary and 34 metastatic tumors) as well as 18 benign lung lesions were analyzed with monoclonal antibody B72.3 using avidin-biotin-peroxidase techniques. Monoclonal antibody B72.3 showed reactivity with 100% of the 27 lung adenocarcinomas and adenosquamous carcinomas, with greater than or equal to 10% of tumor cells showing reactivity in 22 of 27. A lesser percentage of squamous cell carcinomas (24 of 31) and large cell carcinomas (7 of 13) were immunoreactive, and of these several were weakly reactive with less than or equal to 1% tumor cells reacting. In contrast, monoclonal antibody B72.3 failed to react with any of the 21 small cell carcinomas or one carcinoid tumor evaluated. In 35 patients tumor-bearing tissue was resected, and formalin-fixed tissue sections were also evaluated. The staining pattern and percentage of tumor cells positive in the aspiration biopsies were, in most cases, highly predictive of the reactivity observed in corresponding resected tumor. Metastatic adenocarcinomas to lung from various body sites were also immunoreactive with monoclonal antibody B72.3; however, a variety of other tumor types (including 13 melanomas) failed to stain. Staining by monoclonal antibody B72.3 was not noted in any of the 18 benign lesions aspirated, with the exception of occasional fine stippling in the cytoplasm of bronchial epithelial cells. Hence, monoclonal antibody B72.3 and fine needle aspiration biopsy techniques may be of potential use in the differential diagnosis and antigenic phenotyping of a spectrum of lung neoplasms prior to surgical resection.

Adenocarcinoma↗

Expression of the 21,000 molecular weight ras protein in a spectrum of benign and malignant human mammary tissues.

Monoclonal antibodies RAP-5 and Y13-259, directed against the ras gene product [a protein with a molecular weight of 21,000 (p21)] have been used to evaluate ras p21 expression in malignant and benign mammary tissues as well as in the lesions of intermediate stature such as atypical hyperplasia using immunohistochemical assays. Invasive carcinoma demonstrated enhanced expression of ras p21, with generally decreasing expression in carcinoma in situ, atypical hyperplasia, and nonatypical hyperplasia, respectively. Heterogeneous expression of ras p21 was observed among primary as well as metastatic mammary carcinomas. Carcinomas from postmenopausal patients generally demonstrated higher levels of ras p21 than those from premenopausal patients, but no significant difference in ras p21 expression in carcinomas between estrogen-receptor rich and estrogen-receptor poor patients was found. Normal mammary epithelium in terminal duct lobular units from patients with hyperplasia generally demonstrated higher levels of ras p21 expression than did epithelium in large ducts. This demonstration of enhanced ras p21 expression by the epithelium of peripheral lobular portion of the breast is consistent with the previous hypothesis that these areas preferentially undergo malignant transformation. Analyses of the limited number of specimens available from patients with 15-yr follow-up revealed a generally higher level of ras p21 in hyperplasia from patients who subsequently developed carcinoma, as compared to those from patients without carcinoma development. However, no conclusions regarding the potential for malignant transformation could be drawn for any individual patient on the basis of ras p21 expression. Concomitant analyses of ras p21 expression in mammary carcinomas and benign lesions using liquid competition radioimmunoassay and immunohistochemical assay demonstrated the complementary nature of these alternative approaches. These results suggest that enhanced ras p21 expression may be involved in the early stages of mammary carcinogenesis but is probably not involved in the maintenance of the transformed phenotype.

Antibodies, Monoclonal↗