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Biomedical subjects

J M Esteban

Publications and source records attributed to J M Esteban.

At least 37 records · Page 2Linked to original sources
PubMed1994

Predictive value of estrogen receptors evaluated by quantitative immunohistochemical analysis in breast cancer.

To establish the reliability and biologic importance of quantitative immunohistochemical assays for estrogen receptors, more than 200 stage I and II breast cancers were studied. Immunohistochemical analysis was performed using antibody ER 1D5 (AMAC Westbrook, ME) in an automatic stainer (Tech Mate, Biotek, Santa Barbara, CA). Nuclear stain was quantitated by image analysis (SAMBA 4000; IPI, Chantilly, VA). Statistical analyses were performed using Kaplan-Meier product limit estimator for quantitated values and Cox regression for risk for death and disease progression. Estrogen receptor values obtained using the dextran-coated charcoal method were available for comparison. Quantitated immunohistochemical values, expressed as mean optical density of stained nuclei, could discriminate groups of patients that had as much as 3 times higher risk for death and 2.5 times higher risk for disease relapse (P = .006 and P = .018, respectively). Patients could be divided into three risk groups, based on their overall and disease-free survival, that were statistically significant (P = .018). The same analysis was performed using biochemically assayed estrogen receptors values showing that at a cutoff value of 20 fmol/mg, estrogen status predicted overall survival, albeit with lesser probability values (P = .032). These results show that quantitative immunohistochemistry of estrogen receptors provides results that have better predictive value than the biochemically procured ones. This approach not only obviates many pitfalls of the methods requiring tissue homogenates but also allows simultaneous correlation with histopathologic tumor features and expression of other relevant markers.

Breast Neoplasms↗
PubMed1993

Sensitivity and specificity of Gold types 1 to 5 anti-carcinoembryonic antigen monoclonal antibodies: immunohistologic characterization in colorectal cancer and normal tissues.

Carcinoembryonic antigen (CEA) is one of the better-studied oncodevelopmental antigens to which numerous monoclonal antibodies (MoAbs) have been generated. Many of these MoAbs have been recently grouped (Gold classification) according to their epitope recognition. The present study was designed to immunocharacterize various MoAbs, each representative of the five Gold groups, on colorectal cancers and normal tissues using semiquantitative immunohistochemistry. Sensitivity, based on the number of colorectal cancer cases (n = 100) with positive reaction (> 5% cells), was greater with Gold groups 1 and 2 (93% each) than with groups 3, 4, and 5 (78%, 83%, and 87%, respectively). The intensity of the strain also correlated with the Gold groups, with 24%, 20%, and 18% of cancer cases displaying weak or negative staining (0 or 1+) when reacted with MoAbs from groups 3, 4, and 5, respectively, versus 6% and 12% with Gold 1 and 2 antibodies. Cross-reactivity of the anti-CEA antibodies with CEA-related molecules was found to be significant with Gold 5 antibody, which stained most of the normal lung, liver, stomach, and intestinal tissues tested. Strong staining also was seen in granulocytes when they were reacted with Gold 4 and 5 antibodies. The other antibodies showed much less and variable cross-reactivity with normal tissues, with a not statistically significant advantage for Gold 1 antibodies. In addition to lower sensitivity in CEA detection, Gold 3 to 5 MoAbs were less specific due to cross-reaction with one or more of the CEA-related macromolecules expressed by normal tissues. Based on these results and given the broad clinical applications of anti-CEA MoAbs, it is essential to characterize each MoAb to be used for clinical purposes in order to avoid interpretation errors of potential relevance resulting from poor sensitivity/specificity. The use of antibodies that recognize the epitope of group 1 or 2 is recommended to maximize sensitivity and specificity for CEA detection.

Antibodies, Monoclonal↗
PubMed1993

Improvement of the quantification of estrogen and progesterone receptors in paraffin-embedded tumors by image analysis.

It has been shown previously that estrogen receptors (ER) detected by immunohistochemical examination of paraffin-embedded tissue sections could be quantified by computerized image analysis. Several factors were identified that were, in part, responsible for the modest correlation obtained with biochemical assay results. In the present study, 45 formalin-fixed, paraffin-embedded breast carcinomas from a previous study were reevaluated to determine if current methods could provide a better correlation and more consistent results. Sections of the tumors were made to react with estrogen and progesterone receptor antibodies (ER-ICA and PgR-ICA) and the intensity of the stain was quantified using an image analysis system. Vimentin immunostain was used to assess the degree of antigenic loss. Quantitation was performed only on the areas with nuclear staining. The correlation of the estrogen and progesterone receptor values obtained by the dextran charcoal-coated method with the percentages of stained areas and with the intensity of the stain was excellent. The agreement between both methods was 91.1% for estrogen and 86.7% for progesterone receptor values. These results represent a significant improvement compared with those found in a previous study (87% agreement for estrogen receptor). The current approach to estrogen and progesterone receptor quantitation is simplified and eliminates subjectiveness in the selection of the fields for evaluation. The studies are reproducible because discrepancies due to sampling techniques are excluded. Finally, the method validates the technique as a substitute for cytosol-based methods. The results of the two vastly dissimilar assays, the pitfalls of the "gold standard" dextran charcaol-coated assay, and the need for retrospective studies to acquire a range of quantified ER-ICA and PgR-ICA values with clinical significance are discussed.

Breast Neoplasms↗
PubMed1992

Effects of recombinant human gamma-interferon on carcinoembryonic antigen expression of human colon cancer cells.

The effects of human recombinant gamma-interferon (gamma-IFN) on the levels of carcinoembryonic antigen (CEA) expression were investigated in vitro in three human colon adenocarcinoma cell lines (WiDr, HT29, and SW403). Subconfluent cultures were exposed continuously to IFN at concentrations of 1-1,000 antiviral units/ml for up to 6 consecutive days. IFN resulted in a significant increase in CEA levels when assayed by cellular enzyme-linked immunosorbent assay (ELISA), with higher concentrations and longer exposure times resulting in greater CEA enhancement. A three to five-fold enhancement of CEA was observed after 5-6 days of continuous exposures at concentrations of 100-1,000 antiviral units/ml. CEA levels returned to baseline over a 4-day period after discontinuation of IFN. Levels of IFN that resulted in CEA enhancement also resulted in cell growth inhibition, with a direct correlation observed. Flow cytometric studies, which evaluated changes in CEA membrane expression of only the viable cells remaining after IFN exposure, gave similar results to cellular ELISA. Quantitative CEA ELISA, which quantitated changes in total cellular CEA content, demonstrated greater increase in CEA than predicted by cellular ELISA. Continuous IFN exposures for 5-6 days at 1,000 U/ml led to a 96-, 26-, and 5-fold increase in total CEA for the WiDr, HT29, and SW403 cell lines, respectively. WiDr cells exposed to daily 6-h IFN pulses demonstrated intermediate increases in CEA compared with cells exposed continuously to IFN.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

Gamma-interferon enhancement of carcinoembryonic antigen expression in human colon carcinoma xenografts.

Athymic nu/nu mice bearing a subcutaneous human colon cancer xenograft (WiDr, low CEA expression) were treated with gamma-interferon (gamma IFN) at varying doses, frequencies, and periods of duration. CEA content (micrograms/g) and uptake of radiolabeled anti-CEA monoclonal antibody (MAB) (percent injected dose per gram, % ID/g) were measured at 48 h following administration of the MAB, The optimal enhancement of tumor CEA content and tumor localization of [111In] anti-CEA monoclonal antibody (MAB) was seen at gamma IFN doses of 100,000 U i.p. every 8 h for 4 days (4.7 micrograms/g; 29% ID/g) compared to control animals (0.9 micrograms/g; 10% ID/g). The effects of gamma IFN on CEA content and MAB localization were less pronounced when administered (a) at lower doses: 5,000 to 50,000 U i.p. every 8 h, (b) at varying frequencies: 300,000 U/day delivered in divided doses every 4 or 24 h, or (c) for varying periods: 2 or 6 days of therapy. In each case, the biologic effects on tumor CEA content and uptake of [111In]MAB correlated closely with the serum gamma IFN level. Therefore, we conclude that enhancement of in vivo CEA expression by gamma IFN may have clinical relevance for tumor imaging and therapy using radiolabeled monoclonal antibodies.

Animals↗
PubMed1992

Bilateral massive ovarian leiomyomata in a young woman: a case report with review of the literature.

We report a case of ovarian leiomyomata, bilateral and massive, in a 21-yr-old woman. Primary leiomyoma of the ovary is a very rare tumor and is usually small, unilateral, and concomitant with uterine leiomyomata. To our knowledge, this is the first report in the English literature of bilateral ovarian leiomyomata. We document the smooth muscle origin of the tumors with immunohistochemical studies that show appropriate staining with antibodies to vimentin, muscle specific actin, desmin, smooth muscle actin, and collagen type IV. The available literature is reviewed. The characteristics of both typical and atypical ovarian leiomyoma and theories of its origin are discussed.

Adult↗
PubMed1992

DNA ploidy analysis of pleural mesotheliomas: its usefulness for their distinction from lung adenocarcinomas.

The distinction of malignant mesotheliomas from adenocarcinomas with pleural involvement is often difficult, even with electron microscopic and state-of-the-art histochemical and immunologic studies. We evaluated the DNA ploidy and cell cycle of 45 clinically, morphologically, and immunohistochemically well-characterized malignant mesotheliomas to establish their ploidy profile and compared it with that of 41 pulmonary adenocarcinomas. All the cases were mucin negative and had been immunophenotyped with the following monoclonal antibodies: anti-keratin, anti-CEA, anti-Vimentin, anti-HMFG2, Leu M1 (CD15) and B72.3. Single cell suspensions from the paraffin blocks were prepared following Hedley's technique and were analyzed with a Coulter EPICS V flow cytometer. The resulting histograms were interpreted with the Multicycle software program. Five cases were excluded due to their high coefficients of variation. DNA aneuploidy was defined by the presence of more than one G0/G1 peak on the histograms obtained exclusively from the tumor sample. With this criterion, there is a possibility of missing aneuploid cases with a single aneuploid cycling population; however, fixatives and time of fixation produce such a remarkable variation in the fluorochrome uptake that any control, other than normal tissue present in the sample, was rendered unreliable. Five (14%) cases were DNA aneuploid with DNA indexes ranging from 1.2 to 1.9 (mean = 1.5). Three cases had increased S + G2/M values. Of the aneuploid cases, four were epithelial and one sarcomatous. In comparison, aneuploidy was found in 31 (75%) of the lung adenocarcinomas studied (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

Detection of intratumoral aromatase in breast carcinomas. An immunohistochemical study with clinicopathologic correlation.

The expression of aromatase was evaluated in 38 breast carcinomas by an immunohistochemical method (ABC) using an specific polyclonal antibody against human placental aromatase. Fifteen tumors (40%) showed significant immunoreactivity, as defined by cytoplasmic positivity of moderate intensity present in at least 15% of the cells. The results were correlated with the estrogen and progesterone hormone receptor status and several clinicopathologic parameters such as age, tumor size, lymph node status, and stage of the disease. There was a significant, but inverse, correlation between the aromatase activity and the estrogen receptor status (P = 0.04), indicating the likelihood of negative estrogen if substantial aromatase activity was present. No statistically significant correlation was found between the presence of intratumoral aromatase and the rest of the parameters studied (P greater than 0.7). Nor was there a correlation between the aromatase content of the tumors and the menopausal status. The degree of intratumoral heterogeneity of the aromatase content was minimal in six cases where multiple samples from each tumor were analyzed. This is the first study reporting the detection of aromatase in archival material from breast carcinomas using immunohistochemical techniques. The lack of biologic significance of its presence in breast cancer reported here and by others using biochemical assays should be validated in larger series with longer follow-up. The method described can be readily used for that objective.

Aromatase↗
PubMed1991

Comparison of immunoscintigraphy and computerized tomography in identifying colorectal cancer: individual lesion analysis.

Monoclonal antibody scintigraphy with 111In-ZCE025 was used in presurgical staging of 45 patients prior to abdominal exploration for primary, recurrent or metastatic colorectal carcinoma. A total of 186 lesions were identified, of which 147 were evaluated by abdominal surgery and pathology. Sensitivity was 40.5% (49 of 121) for immunoscintigraphy (IS), 61.2% (74 of 121) for computerized tomography (CT), and 72.7% (88 of 121) for IS and CT combined. The positive predictive value was 83.1% (49 of 59) for IS and 88.1% (74 of 84) for CT. Sensitivity of IS was 100% (23 of 23) for primary tumors, 17.7% (11 of 62) for hepatic metastases, and 41.7% (15 of 36) for extrahepatic abdominal metastases. Of the 50 hepatic lesions evaluated by single-proton emission computerized tomography, 11 were localized by IS. Only one was visualized by planar scintigraphy. Sensitivity of CT was 87% (20 of 23) for primary tumors, 67.7% (42 of 62) for hepatic metastases, and 33.3% (12 of 36) for extrahepatic abdominal metastases. Sensitivity of IS combined with CT was 72.6% (45 of 62) for hepatic and 55.6% (20 of 36) for extrahepatic abdominal metastases. Of 24 malignant lesions measured by the pathologist to be less than 3.0 cm (maximum dimension), 7 (29.2%) were detected by IS and 3 (12.5%) by CT. Of 28 malignant lesions greater than 3.0 cm, 23 (82.1%) were detected by IS and 24 (85.7%) by CT. Overall, IS and CT complemented each other in presurgical staging of colorectal carcinoma. IS was of greater value for identification of extrahepatic and small metastases. CT was more effective for identification of hepatic metastases.

Abdominal Neoplasms↗
PubMed1991

Carcinoembryonic antigen expression of resurgent human colon carcinoma after treatment with therapeutic doses of 90Y-alpha-carcinoembryonic antigen monoclonal antibody.

We have previously shown that the colon carcinoma (LS174T) xenografts that emerged shortly after radioimmunotherapy with 90Y-labeled anti-CEA monoclonal antibody (MAb) ZCE025 lacked significant expression of CEA in comparison with the untreated tumors. The present study was designed to establish if the immunophenotype of the treated tumors was the result of CEA specific therapy and if the effect was permanent. Athymic mice bearing LS174T tumors were treated either with 120 mu Ci of 90Y-ZCE025, an equal dose of 90Y-96.5 (nonspecific MAb), or received no treatment. When the treated tumors grew to approximately 1.5 cm in diameter (6 weeks after therapy), they were resected and aliquoted to be transplanted to other mice, plated in tissue culture, fixed in formalin, and homogenized for CEA quantitation. The procedure was repeated 3 times (a total of 4 months after treatment). The CEA content was evaluated 2 and 6 weeks after therapy and when the tumors were transplanted. We confirmed a 4-fold decrease of CEA in the resurgent tumors 6 weeks after specific 90Y-ZCE025 therapy, which was twice the decrease experienced by the tumors treated with nonspecific 90Y-96.5, indicating substantial and specific killing of CEA-expressing cells. The CEA content slowly but progressively increased with each new pass of the tumor in the mice, reaching approximately one-half the value of the controls at the end of the study. The resurgent tumors were also studied by immunohistochemistry with MAbs detecting different epitopes of CEA, keratin, TAG-72, and epithelial membrane antigen to evaluate possible additional immunophenotypic changes induced by radioimmunotherapy. Only the expression of TAG-72 (recognized by MAb B72.3) increased immediately after therapy, but it returned to the original levels by the end of the study. These results suggest that: (a) specific radioimmunotherapy with 90Y-ZCE025 selectively kills cells that express higher levels of CEA; (b) the immunophenotype of the surviving fraction of the tumor appears to slowly revert to its original form; and (c) other tumor markers unrelated to CEA can also be affected. These observations have important implications for the design of radioimmunotherapy trials.

Adenocarcinoma↗
PubMed1991

Interferon enhancement of radioimmunotherapy for colon carcinoma.

Recombinant human gamma-interferon (IFN-gamma) has recently been shown to enhance localization of radiolabeled monoclonal antibodies (MAb) to human colon carcinoma xenografts in athymic mice. The present study investigates the ability of gamma-interferon to enhance radioimmunotherapy of a low carcinoembryonic antigen-expressing human colon cancer (WiDr) in athymic mice. Growth curve analysis, antibody localization, and dose estimation studies were performed. A significant tumor growth delay, measured as the time to reach 1.0 g, was noted for animals receiving specific anti-carcinoembryonic antigen 90Y-MAb (ZCE025, 120 microCi) plus IFN-gamma (61.8 days) as compared to animals that received specific 90Y-MAb with phosphate-buffered saline (34.9 days; P less than 0.005). IFN-gamma (100,000 units) was given i.p. every 8 h for 2 days before and 4 days after 90Y-MAb therapy. The time required to reach 1.0 g for animals treated with nonspecific 90Y-MAb (ZME018) was significantly less either with (38.3 days) or without (34.4 days) IFN-gamma. The difference was more apparent when compared to animals receiving IFN-gamma alone (30.0 days) or phosphate-buffered saline alone (28.9 days; P less than 0.001). Increased antibody localization in the tumors of animals treated with IFN-gamma plus specific 90Y-MAb (43.2% injected dose/g) was seen in comparison to animals treated with specific 90Y-MAb without IFN-gamma (18.2% injected dose/g). The estimate of radiation dose delivered to the tumors, based on biodistribution data over time, revealed significantly higher levels in animals treated with specific 90Y-MAb with IFN-gamma (2477 cGy) compared to animals treated without IFN-gamma (1217 cGy). These results provide support for the use of gamma-interferon as an immunomodulating agent prior to radioimmunotherapy.

Animals↗
PubMed1991

Effects of various fixatives and fixation conditions on DNA ploidy analysis. A need for strict internal DNA standards.

DNA ploidy and cell cycle analyses are being used with increasing frequency as additional, sometimes independent, biologic prognosticators of various malignancies. For obvious reasons, most of the large studies published are retrospective, using archival paraffin-embedded tissues likely to have been fixed and processed differently. To assess the effect of various fixation conditions on ploidy analyses, the authors performed a comprehensive study in which five contiguous aliquots from 26 tissue samples were fixed in formalin for 8. 24, and 48 hours; B5; and the ethanol-based fixative Omnifix (Omni, Xenetics Biomed Inc., Irvine, CA), respectively. The samples were prepared and stained with the use of Hedley's method; the DNA analyses were done with a Coulter EPICS V flow cytometer (Coulter Electronics, Hialeah, FL); and the resulting histograms were interpreted with Multicycle software (Phoenix Flow Systems, San Diego, CA). Mean channels and coefficients of variation (CVs) of the G0/G1 peaks were compared. Increasing fixation times in formalin produced slight shifting to the left on the G0/G1 peaks with differences up to 13 channels. Omni caused similar but more conspicuous changes, with maximal shifting of 51 channels. B5 created the opposite effect, with right-shifted G0/G1 peaks up to 22 channels. The CVs deteriorated progressively with increasing fixation times in formalin. B5 and Omni fixatives conferred the worse histograms, with 6 and 15 cases, respectively, displaying CVs greater than 8. Such significant differences preclude the use of any other internal standard but adjacent normal tissue that was processed exactly the same as the tumor. The validity of DNA results obtained otherwise should be considered questionable. These findings may explain some of the previously published controversial reports and emphasize the need to use an internal standard and more stringent criteria to define aneuploidy in paraffin-embedded tissue.

Cell Cycle↗
PubMed1991

Quantification of estrogen receptors on paraffin-embedded tumors by image analysis.

Emphasis on early detection of breast carcinomas has increased the number of instances in which an insufficient amount of tissue is available for biochemical estrogen receptor (ER) assay. Image analysis, used together with immunohistochemistry, introduces the possibility of quantifying molecules, such as ER, in routinely processed tissues. To explore that possibility, sections from 40 formalin-fixed, paraffin-embedded breast carcinomas with biochemically determined ER values were reacted with H222 anti-ER antibody (ER-ICA) and quantified on a CAS 200 image analysis system. A minimum of ten fields comprising at least 15,000 microns 2 of nuclear area were analyzed in each case. If the antigen distribution were not homogeneous, proportional sampling of the different tumor areas was carried out. Of the 31 ER-positive (10 to 344 fmol/mg) tumors, 27 (87%) were immunoreactive by the ER-ICA assay (greater than 5% positive nuclear area), which represents an improvement over simple microscopic evaluation (68%). Bivariate analyses showed statistically significant, albeit only modest, correlation between ER values and the percentages of positive area (r = 0.556) and positive stain (r = 0.518). The following obstacles were found to interfere with a proper correlation: (a) antigen loss during fixation and processing; (b) intratumoral antigenic heterogeneity; and directly associated with it, (c) interobserver variability. Uniform tissue handling or, alternatively, the use of internal controls to compensate for fixation-induced differences, together with thorough assessment of the tissue, should reduce these obstacles and facilitate accurate and reproducible quantification.

Antibodies, Monoclonal↗
PubMed1990

Spontaneous regression of hepatocellular carcinoma.

A surgically unresectable, biopsy-proven hepatocellular carcinoma (HCC) developed in a 63-year-old man with cirrhosis. He survived 24 months without treatment. During that time the tumor burden decreased as demonstrated both radiologically and by the normalization of alpha-fetoprotein levels. The patient died of complications secondary to repeated esophageal variceal hemorrhage. Necropsy demonstrated prominent, ulcerated esophageal varices and liver cirrhosis without evidence of neoplasia either grossly or on a subsequent thorough microscopic examination. This case represents the first confirmation of HCC spontaneous regression in which a primary histologic diagnosis was confirmed by immunohistochemical and flow cytometric DNA analysis, and where tumor regression was proven by a thorough necropsy examination.

Carcinoma, Hepatocellular↗
PubMed1990

Radioimmunotherapy of human colon carcinomatosis xenograft with 90Y-ZCE025 monoclonal antibody: toxicity and tumor phenotype studies.

Monoclonal antibody ZCE025 recognizes an epitope of the carcinoembryonic molecule (CEA). We have shown that when linked to 90Y, its localization in the tumor was sufficient to result in a significant tumoricidal effect in human colon carcinomatosis grown in the peritoneum of athymic mice. Intraperitoneal tumors were present 7 days after inoculation of the CEA-producing human colon carcinoma cell line LS174T, when the mice received i.p. injections with 40 to 160 microCi of 90Y-labeled ZCE025 or 96.5c (nonspecific monoclonal antibody). The animals that were autopsied 12 days after treatment displayed a significant (P less than 0.001) inhibition of tumor growth when compared to the control animals that received no treatment or similar doses of nonspecific monoclonal antibody. Microscopically, the treated tumors showed extensive radiation effect and they became progressively necrotic until only a rim of viable tissue remained in the periphery of the nodules. CEA expression was practically absent on the newly grown nodules that began to appear 3 weeks after therapy, and remained so 6 weeks thereafter. In contrast, over 80% of the tumor cells from the untreated animals expressed CEA. There was no mortality due to treatment; however, the hematopoietic organs were markedly depleted at the higher doses. The marrow and the spleen recovery began 2 weeks after treatment, and it was completed by the 4th week. No evidence of toxicity was present in any of the other organs examined. These studies suggest that 90Y-ZCE025 therapy results in clonal selection of cells lacking or minimally expressing CEA. The inherent implications of these findings are discussed.

Animals↗
PubMed1990

Immunocytochemical profile of benign and carcinomatous effusions. A practical approach to difficult diagnosis.

One of the great challenges in the cytodiagnosis of effusions is the distinction between reactive mesothelium/histiocytes and cancer cells. This is notably true in patients having undergone radiation and/or chemotherapy. To establish whether monoclonal antibodies (MoAbs) could be used as reliable diagnostic adjuvants, the authors retrospectively and blindly studied 60 cases diagnosed by standard cytologic criteria (malignant, benign, and equivocal), with a panel of seven readily available MoAbs (cytokeratins, vimentin, EMA, B72.3, alpha-CEA, HMFG-2, and Leu-M1) and the lectin Ulex europaeus I. All 18 (100%) malignant cases showed reactivity with EMA and HMFG, whereas 17 (95%) and 11 (61%) reacted with B72.3 and alpha-CEA, respectively. Combinations of (1) EMA + B72.3, (2) EMA + alpha-CEA, and (3) EMA + alpha-CEA + B72.3 displayed positivity in 17 (95%), 11 (61%), and 10 (56%) malignant cases, respectively. Of the 18 benign cases, 7 reacted with HMFG and 2 each with EMA and B72.3. Only one case (5.5%) reacted with both EMA and B72.3. Based on these results, the 24 equivocal cases were regrouped into 14 malignant and 10 benign cases. Follow-up effusions obtained within the ensuing three months in all these patients allowed the authors to unequivocally confirm the diagnosis in all but five. The combination of EMA and B72.3 MoAbs detected malignant cells in 95% of the cases, with a 3.5% incidence of false positive cases in this study. A panel of EMA, B72.3, and alpha-CEA MoAbs should prove the most useful and simple approach to the correct diagnosis in most questionable effusions. Some of the potential pitfalls are discussed.

Antibodies, Monoclonal↗
PubMed1990

Tumor immunophenotype: comparison between primary neoplasm and its metastases.

Monoclonal antibodies (MAb) are firmly established diagnostic adjuvants both in vitro and in vivo. Their potential for immunotherapy is highly promising. Antigenic heterogeneity of cells within the same tumor is a well known phenomenon; however, no large-scale studies are available to ascertain to what degree metastases maintain the immunophenotype of the primary tumors. For that purpose, we studied 54 commonly epithelial malignancies using immunohistochemistry (IHC) with a panel of seven frequently used MAb recognizing a gamut of membrane and cytoplasmic antigens (AE-1, CAM 5.2, B72.3, MC10, anti-carcinoembryonic antigen (anti-CEA), epithelial membrane antigen (EMA), and human milk fat globule (HMFG)). The number of metastases per primary tumor ranged between 1 and 26, with a total of 344 tissues studied. Metastases were located in regional and distal lymph nodes as well as in a diversity of organs (pancreas, adrenal, colon, spleen, soft tissues, etc). Only those cases in which all the tissues were obtained from a single surgical procedure and, therefore, uniformly fixed and processed, were selected. All the metastases from three cases (5.5%) were found to express one or two antigens not present on their primary. In no case did all metastases from a positive primary become negative for one MAb. Twelve cases (18.5%) showed modifications of the phenotype in one or more metastases. This study demonstrates that a broad phenotypic variation does not follow when tumors metastasize, and that it is, therefore, safe to foretell the metastatic immunophenotype based upon that of the primary tumor.

Antibodies, Monoclonal↗