Carcinoembryonic antigen in effusions. A diagnostic adjunct to cytology

A total of 189 effusion specimens (100 benign and 89 malignant) submitted for cytologic examination were assayed for carcinoembryonic antigen (CEA) by an enzyme immunoassay to determine whether the addition of CEA evaluation to cytologic study would improve the diagnostic accuracy for the detection of malignancy. The sensitivity and specificity were 78% and 90%, respectively, for a cytologic diagnosis of malignancy and 68% and 99%, respectively, for a positive CEA (greater than 5 ng/mL). CEA assay was negative in the most common epithelial malignancies of the female genital tract (15 of 17 cases), mesotheliomas (5), lymphomas (7) and alveolar-cell carcinoma of lung (1). CEA assay was positive in 55 of 89 cases of malignancy, including 14 cases with cytologically negative malignant effusions. The CEA assay sensitivity for lung carcinoma (95% for adenocarcinoma, 100% for oat-cell carcinoma and 100% for carcinosarcoma), breast carcinoma (95%), and gastrointestinal carcinoma (100%) were all over 90%. No significant difference in the levels of CEA was noted between gastrointestinal and lung adenocarcinomas. Oat-cell carcinomas and squamous-cell carcinomas had lower values. In cases of an effusion with an unknown primary, an elevated CEA in the fluid is diagnostic of metastatic carcinoma arising from the breast, lung or gastrointestinal tract.     

Diagnostic value of ferritin in the differential diagnosis of malignant effusions

The diagnostic value of ferritin in pleural effusions or ascites was studied in 151 samples from 147 patients (four patients had both kind of effusions). Samples (99 pleural effusions, 52 ascites) were evaluated in 4 groups: benign transudate (27 cases), benign nontuberculous exudate (26 cases), tuberculous exudate (47 cases) and malignant exudate (51 cases). Median ferritin levels in effusions were 67 ng/ml, 805 ng/ml, 889 ng/ml, 998 ng/ml and median effusion/serum (E/S) ratios were 0.7. 2.0, 4.9, 3.2 respectively. There was a significant difference between the concentrations of ferritin in malignant (51 cases) and nonmalignant effusions (100 cases) (p < 0.001), but the specificity and positive predictive value were low (43% and 45% respectively). Ferritin levels in transudate group were significantly lower than those in the others (p < 0.001). However, ferritin concentrations in three exudate groups were similar (p > 0.05). When compared the all inflammatory effusions (malignant, tuberculous, nontuberculous inflammatory exudates) with noninflammatory effusions (transudate and exudate), we determined a significant difference (p < 0.001). CONCLUSIONS: 1) Elevated ferritin concentration in effusions is significant indicators of exudates; 2) It is not good a parameter to discriminate the malignant effusions from the benign ones; 3) They can be useful in the differential diagnosis of the inflammatory exudations from the noninflammatory ones.     

Comparative usefulness of cytology and peroxidase activity in conjunction with carcinoembryonic antigen levels for the diagnosis of mammary cancer

Diagnosis of cancer via measurement of carcinoembryonic antigen (CEA) levels has been unreliable in early neoplastic stages. In order to improve diagnostic reliability, other cytological parameters were examined with CEA. Fifty specimens of effusion fluid were obtained from 40 hospitalized patients and the levels of CEA determined by radioimmunoassay in conjunction with application of an immunoperoxidase procedure. Simultaneous morphologic assessment was performed without knowledge of the immunoassay findings. In 8 documented cases of mammary cancer, all effusion fluid specimens had CEA levels of 16-1074 ng/ml, 7 cases had morphologically positive cells, but only 3 had a peroxidase positive reaction. Except for one case of ovarian papillary adenocarcinoma, the remaining patients were cancer free, had CEA levels of less than 15 ng/ml and only 2 cases (including the ovarian tumor patient) gave positive peroxidase responses. The presence of mammary metastatic duct carcinoma correlated 88% with CEA measurements but peroxidase response was not diagnostically helpful.     

Comparison of biochemical markers between benign and malignant ovarian cysts

To investigate the presumption that earlier diagnosis of ovarian tumors might lead to an improved outcome, we compared several substances in the fluid of benign and malignant ovarian cysts. Our results showed the following: (1) benign cysts were readily separated from malignant cysts on the basis of total lactate dehydrogenase (LD) activity and except for mucinous cysts, by their isoenzyme patterns. (2) Preoperative serum total LD activity and LD isoenzymes were of no diagnostic help in predicting the malignant tumors. (3) Carcinoembryonic antigen (CEA) levels usually differed greatly between benign and malignant cysts, although the benign mucinous cysts had CEA levels indistinguishable from malignant cysts. (4) Prominent quantitative differences between Roche and Abbott CEA activity were present in both benign and malignant cysts. (5) Preoperative serum CEA levels were not helpful in differentiating the benign from the malignant cysts.     

DNA analysis of malignant effusions. Comparison with cytologic diagnosis and carcinoembryonic antigen content.

Twenty-three consecutive malignant effusions from 19 patients submitted for cytologic examination were analyzed for carcinoembryonic antigen (CEA) content and for DNA analysis by flow cytometry. The study was undertaken to determine if the addition of DNA analysis would improve the sensitivity of cytologic diagnosis and CEA assay. CEA examination was performed on Papanicolaou-stained smears and hematoxylin-and-eosin-stained cell blocks. Final diagnoses were correlated with histologic examination (four patients), clinical and radiologic studies, and follow-up. The malignant effusions in 19 patients were secondary to carcinoma of the breast (5), lung (5), ovary (1), endometrium (1), mucinous carcinoma of the colon (1), unknown primary (1), extraovarian papillary carcinoma (1), mesothelioma (2) and large cell lymphoma (2). The sensitivity of cytologic diagnosis was 100% and specificity 100%. DNA aneuploidy, defined as the presence of two separate peaks in the histogram, was present in 7 of 23 fluids (sensitivity, 30%). Four fluids had insufficient cells for analysis, and one histogram showed debris (following chemotherapy). DNA aneuploidy was detected in effusions secondary to carcinoma of the breast (4), lung (1) and lymphoma (2). Using 5 ng/mL as the cutoff, the sensitivity of CEA was 68%. DNA analysis of cells in malignant effusions is less sensitive than cytologic diagnosis, and CEA assay and is not recommended for routine use in the diagnosis of malignant effusions.     

AFP, CEA, CA 19-9 and TPA in hepatocellular carcinoma.

The present study is based on the assay of four markers (AFP, CEA, TPA, Ca 19-9) using IRMA methods in 36 normal subjects, 44 cirrhosis and 66 HCC patients. Parametric and non parametric tests were used to test differences and correlations. ROC curves and discriminant functions were also elaborated. Normal 95% "cut-off" was determined by the "boostrap" method yielding: CEA 3.4 ng/ml; Ca 19-9 55 U/ml; TPA 58U/l and AFP 5.2 ng/ml. In HCC patients the values of the four markers were, on average, significantly different from those of normal subjects. However, only AFP and TPA exhibited high diagnostic accuracy (90%) for detection of the tumor. Higher than normal mean values for all markers were, also observed in cirrhotic patients. Only AFP yielded effective discrimination between HCC and cirrhosis. The positive prediction for the presence of the tumor on cirrhotic ground was 95% for AFP values higher than 18.5 ng/ml, with a 78% negative predictive value with a 6 ng/ml threshold. Association of AFP with TPA showed only a marginal diagnostic improvement. Results were not improved at all by combining CEA and Ca 19-9 with AFP and/or TPA. In conclusion, AFP is and remains the best marker for HCC and the only one effective in discriminating of HCC from cirrhosis. TPA may be considered a valid alternative if cirrhosis is not present. CEA and Ca19-9 are of no use.     

Specific tumor markers in diagnostic cytology. Immunoperoxidase studies of carcinoembryonic antigen, lysozyme and other tissue antigens in effusions, washes and aspirates

The immunoperoxidase technique was used to identify specific tumor markers in exfoliated cells in fine needle aspirates and body fluids. Carcinoembryonic antigen (CEA) and lysozyme staining was evaluated in cytocentrifuge preparations from 42 malignant effusions and aspirates and 16 benign effusions. Reactive mesothelial cells were negative for CEA and lysozyme or showed faint peripheral cytoplasmic staining. Malignant cells from 50% of the adenocarcinomas studied were positive for CEA. All tumors studied were negative for lysozyme. These staining patterns are helpful in the differential diagnosis of reactive mesothelial and adenocarcinoma cells, a frequent diagnostic dilemma. Moreover, demonstration of specific tumor antigens (e.g., prostatic acid phosphatase, calcitonin and immunoglobulin) helped define the origin of metastatic malignancy in selected cases. Estrogen receptor activity was also identified in tumor cells using this technique. Immunoperoxidase was helpful in the evaluation of malignant cytologic specimens from patients with more than one tumor. Interpretation of staining patterns is discussed, with reference to the limitations of the technique. Immunoperoxidase methods maintain cytologic detail, are readily adaptable to diagnostic cytology and increase the specificity of cytologic diagnosis.     

Irisin and Carcinoembryonic Antigen (CEA) as Potential Diagnostic Biomarkers in Gastric and Colorectal Cancers

Background:Carcinoembryonic antigen (CEA) is a common gastrointestinal tumor biomarker. Irisin is adipo-myokines that has been suggested to have a potential role in cancer development. However, limited studies test irisin as biomarker in gastric and colorectal cancers. Therefore, this study aims to investigate whether CEA and irisin could be a potential diagnostic biomarker in gastric and colorectal cancer.Methods:A case-control study consists of 90 subjects, 21 gastric cancer patients, 49 colorectal cancer patients and 20 control. Serum CEA was detected by fluorescence immunoassay (FIA) kit. Serum irisin was determined by enzyme-linked immunosorbent assay (ELISA) kit.Results:Serum CEA increases significantly and serum irisin decreases significantly in gastric and colorectal cancer patients. According to Receiver Operating Characteristic (ROC) curve analysis, in gastric cancer, the area under curve of CEA is 1.00 (95% CI, 1.000-1.000, p< 0.0001). The diagnostic cut-off of CEA is< 3.08 ng/ml with %100 sensitivity and 100% specificity. The area under curve of irisin is 0.94 (95% CI, 0.8177-1.000, p< 0.0001). The cut-off of irisin is> 30.2 ng/ml with %90 sensitivity and 100%, specificity. In colorectal cancer, the area under curve of CEA is 0.99 (95% CI, 0.9866-1.000, p< 0.0001) and the diagnostic value< 2.6 ng/ml with %98 sensitivity and %100 specificity. The area under curve of irisin is 0.96 (95% CI, 0.9155-1.000, p< 0.0001). The diagnostic cut-off of irisin is> 41.9 ng/ml with 88.1sensitivity and 90.5 specificity.Conclusion:CEA and irisin could be powerful potential diagnostic biomarkers which would be use for early detection of gastric and colorectal cancers.Key Words: Biomarker, Carcinoembryonic antigen (CEA), Colorectal cancer, Gastric cancer, Irisin     

Efficiency of composite laboratory tests in the diagnosis of liver malignancies

The utility of the markers CEA, beta-HCG, CA-50, alpha-fetoprotein (APF), ferritin, alkaline phosphatase (AP), its isoenzyme liver-1 (APL1), gamma-glutamyltransferase (gGT), its fast migrating isoenzyme (gGT1) and 5'nucleotidase (5'N) in differentiating liver malignancies and benign involvement was evaluated in the sera of 85 patients with hepatocellular carcinoma (HCC), 157 with chronic liver disease (CLD) and 91 with liver metastases (LM) derived from different tumors. The mean concentrations of all the parameters except CEA and GGT1 were significantly different in HCC and CLD, but a broad overlap existed in the two groups, so different cut-offs were considered to assess the positive and negative predictive values and test efficiency (Eff). The best results were observed considering AFP greater than 100 IU/m (Eff0.86), ferritin greater than 800 ng/ml (Eff0.69), CA-50 greater than 100 U/ml (Eff 0.63), beta-HCG greater than 10 mU/ml (Eff 0.61), AP greater than 300 IU/ml (Eff 0.66), the presence of APL1 (Eff 0.78), 5'N greater than 25 mU/ml (Eff 0.70), gGT greater than 100 mIU/ml (Eff 0.63). Among HCC patients 17% did not secrete AFP; in 26% the protein was less than 100 IU/ml and in 36% less than 400 IU/ml. Apart from AFP the most effective marker was APL1. At the above cut-offs more than three parameters were simultaneously positive in 71% of HCC and 9.9% of CLD. CEA, CA50, AFP were the only parameters that distinguished the HCC from the LM group; in the latter, APL1 was also a very sensitive marker (87%) for neoplastic involvement of the liver.     

Characterizing subpopulations of neoplastic cells in serous effusions. The role of immunocytochemistry

OBJECTIVE: To analyze the role of immunochemistry in serous effusions. STUDY DESIGN: We analyzed cell blocks of 18 pleural and 18 peritoneal effusions diagnosed as malignant (18), benign (14) and suspicious (4). They were immunostained by the avidin-biotin complex method with a panel of four monoclonal antibodies--CEA, Ber-EP4, LeuM1 (CD15) and p53--and, for lectins (Ulex europaeus) UEA-l, ConA and ConBr. RESULTS: Seventeen of the 18 cases of adenocarcinoma were positive for CEA (95%), 12 (66.6%) for Ber-EP4, 11 (61%) for CD15 and 11 (61%) for p53. Twelve of the 18 (66.6%) were positive for UEA-1, CEA, Ber-EP4 and CD15. UEA-1 did not react with mesothelial cells. p53 Gave a positive reaction in only one case, reactive mesothelial cells. ConA and ConBr reacted indiscriminately with benign and malignant cells; thus, it was not useful in distinguishing between these cells. CONCLUSION: In this context no antibody used alone is reliable for corroborating a diagnosis, but the selective use of a small panel of three markers (CEA, Ber-EP4 and LeuM1) can be very useful in solving diagnostic difficulties in the cytodiagnosis of serous effusions.     

Increased levels of albumin in bronchial washing fluid of patients with bronchial carcinoma. Could albumin be considered as a tumor marker?

BACKGROUND: The aim of this study was to evaluate the significance of albumin in bronchial washing fluid (BWF) and its relationship to three tumor markers (CEA, CA 19-9 and NSE). METHODS: Serum and BWF samples were collected in a group of 60 patients. Albumin and tumor markers in the BWF and serum of three groups: a control group (CG), a chronic bronchitis group (CBG) and a lung cancer group (CaG), were analyzed in a prospective cross-sectional study. The diagnostic yields of the tests in each environment (serum and BWF) were evaluated by using as cutoff points the values of the corresponding 90th percentile of CG and CBG taken together. RESULTS: A significant difference in albumin level (p < 0.001) was noted in the BWF of patients with cancer compared with the other two groups. In addition, a significant difference in CEA level (p < 0.001) was observed in the serum of cancer patients compared with the other two groups. The cutoff values for CEA in serum and albumin in BWF were 2.20 ng/mL and 2.00 g/dL, respectively. The areas under the corresponding ROC curves were 93% and 97%. Combination of CEA-serum and albumin-BWF by logistic regression analysis increased their diagnostic value. CONCLUSION: Measurement of albumin levels in BWF could be a useful additional diagnostic tool to differentiate malignant from non-malignant lung diseases. Moreover, the combined measurement of CEA in serum and albumin in BWF could be of aid in the follow-up of lung cancer patients.     

Cystatins C,E/M and F in human pleural fluids of patients with neoplastic and inflammatory lung disorders

Secretory type 2 cystatins, like cystatins C, E/M and F, are thought to be involved in many pathobiological processes, including vascular amyloidosis, rheumatoid arthritis, Alzheimer's disease, osteoporosis, viral and bacterial infections, inflammatory disorders and tumour invasion and metastasis. In order to define the levels of cystatins C, E/M, and F in pleural effusions and to investigate whether these cystatins correlate with diagnostic parameters of pleural and lung diseases, we determined their concentrations in 160 pleural effusions. The median concentration of cystatin C in pleural effusions was 1437 microg/l (95.8 nM), ranging between 18-3967 microg/l. Cystatin C did neither correlate with malignant nor with benign diseases. The concentration of cystatin E/M was significantly higher in effusions of primary pleural tumours (mesotheliomas) compared to secondary pleural tumours and benign diseases. Furthermore, there was a significant correlation between the concentration of cystatin E/M of mesotheliomas and the pleural fluid tumour cell count and of cystatin C. The median values of cystatin F were significantly increased in parapneumonic/empyema thoracis pleural effusions and tuberculous pleurisy compared to malignant pleural effusions, respectively. The concentration of cystatin F in benign effusions correlated significantly with diagnostic parameters and inflammation (total protein; lactate dehydrogenase; C-reactive protein). Finally, only in the group of parapneumonic/empyema thotatin F and the neutrophil count. In conclusion, pleural effusions of different origin contain high levels of cystatin C, perhaps constituting the major part of an inhibitor reservoir. The level of cystatin E/M appears to be significantly associated with primary pleural tumours and cystatin F correlates with inflammatory processes of lung disorders.     

Elevated CEA and CA19-9 serum levels independently predict advanced pancreatic cancer at diagnosis

Abstract

Purpose: It is suggested that tumour markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) could be used to predict the stage of pancreatic cancer. However, optimal cut-off values for CEA and CA19-9 are disputable. This study aimed to assess the value of CEA and CA19-9 serum levels at diagnosis of pancreatic ductal adenocarcinoma (PDAC) as predictors for the advanced stage of PDAC in patients discussed at pancreatic multidisciplinary team (MDT) meetings.

Methods: Patients with suspected PDAC discussed at MDT meetings from 2013 to 2017 were reviewed, in order to determine optimal cut-off values of both CEA and CA19-9.

Results: In total, 375 patients were included. Optimal cut-off values for predicting advanced PDAC were 7.0?ng/ml for CEA and 305.0?U/ml for CA19-9, resulting in positive predictive values of 83.3%, 73.6%, and 91.4% for CEA, CA19-9 and combined, respectively. Both tumour markers were independent predictors of advanced PDAC, demonstrated by an odds ratio of 4.21 (95% CI:1.85–9.56; p?=?0.001) for CEA and 2.58 for CA19-9 (95% CI:1.30–5.14; p?=?0.007).

Conclusions: CEA appears to be a more robust predictor of advanced PDAC than CA19-9. Implementing CEA and CA19-9 serum levels during MDT meetings as an additional tool for establishing tumour resectability is worthwhile for tailored diagnostics.     

血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断价值分析

摘要 目的：探讨与分析血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断价值。方法：2019年8月到2022年5月选择在本院诊治的消化道恶性肿瘤患者150例作为消化道恶性肿瘤组,同期选择在本院体检的健康人群150例作为健康组。采集两组人群的血清癌胚抗原（CEA）、糖类抗原19-9（CA19-9）、C-反应蛋白（CRP）含量,调查患者的病理特征并判断诊断价值。结果：消化道恶性肿瘤组的血清CEA、CA19-9、CRP含量都高于健康组（P<0.05）。消化道恶性肿瘤组的CEA、CA19-9、CRP阳性率为54.7 %、58.7 %、60.7 %,高于健康组的3.3 %、4.0 %、4.7 %（P<0.05）。在消化道恶性肿瘤组中,不同组织学分化、临床分期、淋巴结转移患者的血清CEA、CA19-9、CRP含量对比有差异（P<0.05）。血清CEA、CA19-9联合CRP诊断为阳性113例,在健康组中诊断为阳性3例,血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断敏感性与特异性分别为75.3 %（113/150）和98.0 %（147/150）。结论：消化道恶性肿瘤患者多伴随有血清CEA、CA19-9、CRP的高表达,病理特征与血清CEA、CA19-9、CRP含量存在相关性,血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断敏感性与特异性都比较好。     

Evaluation of specific antigen and prostatic acid phosphatase specificity. Study of false values

We assayed prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) serum levels in 1305 subjects without malignant prostatic pathology by double antibody RIA I125 to evaluate their specificity. When we set a second upper normal limit of 10 ng/ml for PSA and 2.5 ng/ml for PAP there was a significant increase of specificity. There were 2 and 3.7% false positive results in non-prostatic benign pathologies, 1.8 and 7.9% in non-prostatic malignant, 3.5 and 4.7% in non-complicated benign prostatic hypertrophy (BPH) and 3.3% for both in chronic prostatitis. In patients with complicated BPH and acute prostatitis the results were 64.8 and 24% for PSA and 20 and 16% for PAP. In conclusion, PSA is more specific than PAP in patients without acute inflammatory pathology of the prostate; the high rate of false positive values in the latter excludes its usefulness in these patients as diagnostic tumoral markers.     

Immunophenotyping of Mesothelial Cells and Carcinoma Cells With Monoclonal Antibodies to Cytokeratins, Vimentin, Cea and Ema Improves the Cytodiagnosis of Serous Effusions

This paper presents an immunocytochemical study performed on cytocentrifuged deposits from 109 peritoneal and pleural effusions including 20 transudates, 43 malignant metastatic effusions and 46 effusions containing atypical cells, unidentifiable as reactive mesothelial or malignant epithelial cells on the classical morphological criteria. A panel of four monoclonal antibodies (MAb) was used, including KL1 directed to cytokeratins (KER), V9 to vimentin (VIM), NEO 723 to carcinoembryonic antigen (CEA) and E29 to epithelial membrane antigen (EMA). In most transudates the reactive mesothelial cells coexpressed VIM and KER with a ring-like pattern for the latter proteins. In contrast, they were unreactive to anti-CEA and weakly and inconsistently reactive to anti-EMA. In malignant effusions, most carcinoma cells coexpressed EMA, CEA and KER with a predominant diffuse cytoplasmic pattern for the latter. Only a few malignant epithelial cells from five metastatic adenocarcinomas weakly expressed VIM. When used on the 46 effusions with unidentifiable cells, the panel of MAb allowed reactive mesothelial cells and malignant epithelial cells to be distinguished from each other in 39 of 46 cases (85%).     

CEA serum levels in non-neoplastic disease.

Several non-neoplastic conditions, i.e., acute and chronic inflammations, benign tumors, renal or hepatic insufficiency, are associated with elevated plasma levels of Carcinoembryonic Antigen (CEA). Usually, CEA elevation in these pathologies is less than 10 ng/ml. CEA values in non-malignant disease can be affected by many factors, which can be classified into five main categories: a) tissular, b) physiological, c) metabolic, d) circulating and e) methodological factors. Synthesis, expression and release are the most important tissular factors. Among the metabolic ones liver, biliary and renal functions play a primary role in the determination of CEA concentrations. In addition, other factors such as the presence of circulating CEA-like substances, autoantibodies and immunocomplexes or the characteristics of the assay method can influence the diagnostic value of the CEA test. All these factors must be carefully considered when the marker is used in clinical practice.     

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients

The schistosomal parasite plays a critical role in the development of malignant lesions in different organs. The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for disease detection. The objective of this paper is to evaluate certain biochemical parameters as diagnostic tools to efficiently differentiate between colonic carcinoma and colonic carcinoma associated with schistosomal infection among Egyptian patients. The parameters under investigation are interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α), carcinoembryonic antigen (CEA) levels, tissue telomerase, pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase (LDH) enzyme activities. The results revealed a significant elevation in the level of the tumour markers IL-2, TNF-α and CEA as well as the activities of LDH, telomerase and G-6-PD among non-bilharzial and bilharzial colonic cancer groups, with a more potent effect in bilharzial infection-associated colonic cancer. A significant inhibition in PK activity was recorded in the same manner as compared to normal tissues. The efficacy of this biomarker was also evaluated through detecting sensitivity, specificity, negative and positive predictive values. In conclusion, schistosomal colonic carcinoma patients displayed more drastic changes in all parameters under investigation. The combination of the selected parameters succeeded in serving as biomarkers to differentiate between the two malignant types.     

Morphometric differences between cytologically benign and malignant serous effusions

The morphometric differences between benign and malignant serous effusions, as diagnosed by standard cytologic criteria in 95 unselected cases (50 benign and 45 malignant), were studied using the IBAS semi-automated image analysis system, which calculates various parameters from tracings of cellular and nuclear outlines. Fourteen cases were also stained for cytokeratin proteins (with the CAM 5.2 antibody) by the immunoperoxidase technique and reanalyzed for positive cells. Significant differences were found for mean values between cytologically benign and malignant cases for cellular and nuclear areas, perimeters and maximum diameters, but not for two form factors. Some differences were enhanced in the CAM 5.2-stained cases. Real morphometric differences in samples of cells from benign and malignant cases are the basis of cytologic diagnosis. Fully automated diagnostic systems could operate on arbitrary threshold values, but there is considerable overlap in specimen means for all parameters between benign and malignant cases.     

The value of the immunoperoxidase slide assay in the diagnosis of malignant pleural effusions in breast cancer

Whether immunocytochemical studies of malignant pleural effusions due to breast cancer would increase the diagnostic yield as compared with conventional effusion cytology was examined in 30 cases with biopsy-proven metastatic spread to the pleura. Conventional cytology was performed on air-dried smears as well as on cytocentrifuge preparations stained with the May-Grünwald-Giemsa stain. Immunocytochemistry was performed with monoclonal antibodies against carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and human leukocyte antigen (HLA) and the peroxidase-antiperoxidase technique on glass slides after Ficoll-Hypaque centrifugation. By conventional cytology, 13 cases (43%) were positive for malignant cells, 6 cases (20%) were suspicious, and 11 cases (37%) were negative. In marked contrast, all 30 cases were immunocytologically positive for malignancy. Tumor cells in all cases demonstrated a positive reaction for EMA. Some mesothelial cells were also positive for EMA, but their reaction pattern was clearly distinguishable from that of the tumor cells. Twenty-one cases (70%) also showed CEA-positive tumor cells; mesothelial cells never reacted with CEA. Some tumor cells showed a loss of HLA expression. In conclusion, this immunocytologic method can be recommended as a routine procedure for greatly increasing the diagnostic yield of cytology in pleural effusions due to breast cancer.