Immunoperoxidase Staining For Carcinoembryonic Antigen Research Articles

An immunohistochemical study of the incidence and significance of carcinoembryonic antigen in malignant endometrium.

In an immunohistochemical study of the presence of carcinoembryonic antigen (CEA) in endometrial carcinomas, it was found that CEA was detectable in 92 of 171 neoplasms, an incidence of 53.8%. The antigen was unrelated to important prognostic variables, both clinical and histopathologic, and overall there was no difference in survival rates between CEA-positive and CEA-negative endometrial neoplasms during the 10-year follow-up period. CEA-negative carcinomas did, however, confer longer survival in certain subgroups of patients: those with adenocarcinomas arising from a hyperplastic endometrium, those with neoplasms of poor differentiation, and those who, in addition to surgery, received irradiation treatment. It is suggested that immunoperoxidase staining for CEA may provide an independent method for predicting radiosensitivity in endometrial carcinomas, and also may be indicative of prognosis within some forms of this malignancy.

Restaging of colorectal cancer based on the identification of lymph node micrometastases through immunoperoxidase staining of CEA and cytokeratins

The present study was performed to identify tumor cells in lymph nodes from colorectal adenocarcinomas considered free of disease by the classic hematoxylin-eosin stain, based on the detection of the carcinoembryonic antigen (CEA) and cytokeratins in neoplastic epithelial cells. For this purpose, 603 lymph nodes from 46 lesions were stained by the peroxidase-antiperoxidase technique. Tumor cells were detected in 22 nodes from 12 patients, mainly in the subcapsular sinuses, permitting a restaging of these patients into two groups: those now considered to have metastatic disease and those free of metastases. However, the 5-year follow-up showed no statistical differences in survival between the two groups.

Carcinoembryonic antigen in basal cell neoplasms in black patients: An immunohistochemical study

The development of skin cancer in black persons is rare, and basal cell epitheliomas are the most uncommon. Eight tumors were evaluated by routine histochemistry examination and immunoperoxidase staining for carcinoembryonic antigen (CEA). Our results demonstrate that half these tumors showed a positive reaction to this antigen, supporting the adnexal origin/differentiation of these lesions. Sixteen (16/18) similar tumors from white patients failed to show equivalent features. In addition, some of these CEA-positive tumors seem to demonstrate less aggressive behavior.

Xenografting of normal colonic mucosa in athymic mice

Colonic mucosa was implanted subcutaneously into nude mice in order to investigate the potential use of xenografts as an in vivo model system for the study of colonic epithelial proliferation and differentiation. The xenografts were followed for 5 weeks. Proliferation was studied by bromodeoxyuridine (BrdU) incorporation followed by visualization of the DNA-synthesizing cells with an anti BrdU monoclonal antibody. Differentiated cells were visualized by histochemical staining of goblet- and enterochromaffin cells and of columnar cells by immunoperoxidase staining for carcinoembryonic antigen (CEA), secretory component, and serotonin. In different strains of mice different observations were made. Less immunocompetent strains (Balb c nu/nu, NMRI nu/nu) developed abscesses at the site of the xenograft as well as wasting disease. These phenomena almost never occurred in CD-1 nu/nu mice. The success rate was highest in CD-1 nu/nu mice. After about 1 week, only crypt base cells remained vital and started to repopulate crypts with epithelial cells showing normal colonic differentiation features such as CEA, secretory component, and serotonin immunoreactivity and mainly sulphomucin production. After longer periods of time, crypts started to form cyst-like structures due to accumulation of secretion products and dead cells. DNA-synthesizing cells were seen in the basal areas of recognizable crypts and in the cyst-like structures in a random distribution. These results indicate that normal colon mucosa xenografted into nude mice maintains its proliferative and differentiating capacity for at least 5 weeks.

Amiodarone-Associated Pulmonary Toxicity: A Clinical and Pathologic Study of Eleven Cases

The new anti-arrhythmic agent, amiodarone, is increasingly recognized as a cause of pulmonary toxicity (APT). In the present series, 11 of 171 patients (6.4%) receiving the drug had APT develop. Clinical symptoms varied from mild cough and dyspnea to acute respiratory failure. Chest x-rays demonstrated alveolar and/or interstitial opacities in all 11 patients. The microscopic appearance of APT resembled that seen in lung injury from other drugs. The features were those of diffuse alveolar damage, ranging from the early acute to the organizing phase. Mural and intraalveolar foam cells were a prominent component. The epithelial origin of these cells was confirmed by positive immunoperoxidase staining for carcinoembryonic antigen. They were further identified as type II pneumocytes by electron microscopic examination. These findings support the concept that amiodarone is responsible for a drug-induced phospholipidosis. APT was clinically reversible in all patients; however, five patients (45%) died of arrhythmia shortly after discontinuation of amiodarone.

A case of clear cell adenocarcinoma of the uterine cervix in pregnancy

An extremely rare case of clear cell adenocarcinoma of the uterine cervix in pregnancy is reported. The primary lesion was first found at 34 weeks of pregnancy in a 34-year-old patient, and was cytologically suspected to be malignant. At 39 weeks of pregnancy, the patient underwent abdominal cesarean section concomitantly with removal of huge right ovarian tumor (3050 g) and delivered a normal male baby weighing 3590 g. Histological findings for cone biopsy at 22 days postpartum revealed invasive adenocarcinoma, and abdominal radical hysterectomy and pelvic lymphoadenectomy were performed at 36 days postpartum. Microscopically, the tumor tissue was composed of clear and hobnail-type cells. It showed a considerable amount of PAS-positive diastase-labile glycogen but was only weakly positive for immunoperoxidase staining of carcinoembryonic antigen.

Immunoperoxidase staining of carcinoembryonic antigen as a prognostic indicator in colorectal carcinoma.

Immunoperoxidase staining for carcinoembryonic antigen (CEA) was performed on 192 colorectal carcinomas to determine: whether tissue staining can be substituted for preoperative serum CEA levels, and whether patient survival can be predicted by these parameters. The overall incidence of positive tissue staining was 75 percent, which was similar to the elevated serum level percentage of 73 percent. Both the serum CEA level and the CEA tissue stain correlated with patient survival in Dukes' stage C patients. There was no correlation between tissue CEA stain and tumor differentiation. Positive tissue stain and elevated preoperative serum CEA identified patients with poor prognosis in Dukes' stage D only. This study shows that tissue staining with immunoperoxidase may be substituted for preoperative serum levels for CEA. The combination of these two parameters, however, does not identify patients at greater risk for recurrence than either procedure alone.

Immunoperoxidase staining of carcinoembryonic antigen with monoclonal antibodies in adenocarcinoma of the colon.

Mouse monoclonal antibodies to carcinoembryogenic antigen (CEA) obtained by the somatic cell hybridization technique of Köhler and Milstein were used in a modified enzyme bridge immunoperoxidase staining method. Both high and low affinity antibodies were tested and their staining properties compared with those of a commercial polyvalent rabbit antiserum. The staining pattern of neoplastic epithelial cells in all seven antibodies in samples of primary adenocarcinoma of the colon was similar, indicating that no gross differences were found in the exposure of the different antigenic determinants of CEA in formalin fixed tissue. The background staining of the monoclonal antibodies are negligible. It is concluded that monoclonal antibodies are superior to conventional antisera in immunoperoxidase staining of CEA.

Immunoperoxidase staining for carcinoembryonic antigen in small cell carcinoma of the lung

Diagnostic pretreatment biopsies in 53 patients with small cell carcinoma of the lung (SCCL) were examined retrospectively for presence of carcinoembryonic antigen (CEA). The unlabelled antibody-enzyme (PAP) technique was utilized. All patients had been treated with intensive chemotherapy. The patients were divided into 3 groups according to the immunoperoxidase staining reactions of the biopsies. Thirteen (24.5%) patients had biopsies that were strongly positive for CEA while 22 (41.5%) had slightly positive and 18 (34%) had negative biopsies. The patients with biopsies strongly positive for CEA had a significantly longer survival as compared with patients with negative staining results ( P < 0.05). No significant correlation was observed between immunoperoxidase staining for CEA and morphological subtypes of SCCL according to the WHO 1977 classification.

Immunocytochemical localization of carcinoembryonic antigen in benign and malignant colorectal tissues. Assessment of diagnostic value.

Immunoperoxidase and immunofluorescence staining for carcinoembryonic antigen (CEA) was performed on paraffin and frozen sections, respectively, of colonic carcinomas (70), liver and lymph node metastases (20), mesenteric nodes (150), mucosa adjacent to carcinoma (40), colonic resection margins (20), normal colon (ten), and colorectal polyps (64) in order to assess its potential diagnostic value. On the basis of this study of the immunocytochemical localization of CEA in colorectal tissues, conclusions were as follows. (1) Localization of CEA to glycocalyx of surface epithelial cells is a normal finding in the colon and is similar in normal colon and mucosa distant and adjacent to infiltrating carcinoma. (2) Although strongly positive cell surface and intraluminal staining frequently correlates with the presence of carcinoma in neoplastic polyps, it is not by itself a reliable diagnostic criterion. (3) Failure to demonstrate CEA in a gland-forming carcinoma makes a diagnosis of colorectal carcinoma unlikely. (4) Poorly differentiated colorectal carcinoma usually contains much less demonstrable surface CEA, but may occasionally stain cytoplasm strongly. (5) Although lymph node micrometastases from colorectal carcinoma are readily demonstrated by immunoperoxidase staining for CEA, screening of hematoxylin and eosin-stained sections by a competent pathologist appears to be adequate for their detection.

Immunoperoxidase staining for carcinoembryonic antigen in colonic carcinoma, osteosarcoma, and chordoma.

An indirect immunoperoxidase method was used in an attempt to detect carcinoembryonic antigen (CEA) in 17 well-differentiated colonic adenocarcinomas, five osteosarcomas, and four chordomas. Fifteen of the adenocarcinomas were positive, and five of them had been fixed and embedded in 1952 and one in 1942. Two other adenocarcinomas from 1942 were not positive. CEA was not demonstrated in any of the osteosarcomas or chordomas.

Carcinoembryonic antigen in carcinoma of the uterine cervix2. Tissue localization and correlation with plasma antigen concentration

Immunoperoxidase staining for carcinoembryonic antigen (CEA) was performed on the tumors of 241 patients with invasive carcinoma of the cervix. Positive tissue staining indicative of a CEA concentration of at least 3 microgram/gm was present in 154 tumors (63%) as opposed to 0 of 30 specimens of normal cervix (p less than .001). Plasma CEA values were obtained at the time of tissue staining on all patients. Plasma CEA concentration was related more directly to total tumor burden (tumor CEA content x extent of disease) than to tumor CEA concentration alone. Progressively rising plasma CEA levels predicted recurrent disease in over 80% of patients whose tumors stained positively for CEA. In contrast, serial plasma CEA values correlated positively with clinical disease status in only 28% of patients whose tumors were devoid of CEA. Immunoperoxidase staining of tissue specimens identifies those patients whose tumors contain high levels of CEA and who therefore should benefit most from subsequent plasma antigen determinations.

Carcinoembryonic antigen in malignant and nonmalignant gynecologic tumors.Circulating levels and tissue localization

Carcinoembryonic antigen (CEA) was determined in the serum and tissues of patients with gynecologic tumors utilizing radioimmunoassay and immunoperoxidase techniques. Among 328 patients with gynecologic cancer the serum CEA concentration was elevated over the normal background level of 5 ng/ml in 32 cases (9.8%), and the frequency of elevated CEA levels increased with advancing clinical stage. Among 84 patients with benign tumors CEA was elevated in 5 cases (6%). Elevated levels were most commonly seen in patients with ovarian cancer (20%). In squamous cell carcinoma of the uterine cervix elevated levels occurred in 10%, and in cervical adenocarcinoma CEA elevation took place in 19% of the cases. In endometrial cancer CEA became less frequently elevated (7%). After radical surgery the CEA concentration decreased and remained low in 20 of 24 cancer patients (83%). Fifteen of these remained clinically tumor free during the follow-up period of 4–24 months. Three of four patients whose CEA concentration did not significantly decrease after operation were found to have residual tumor. Radiotherapy resulted in an increased CEA concentration in 3 of 5 patients with advanced cancer. Immunoperoxidase staining of CEA was carried out in formalin-fixed paraffin-embedded sections of 64 tumors and 33 specimens from normal genital tract. Tissue CEA was demonstrable in early as well as in advanced stages of malignant tumors. All normal tissue specimens from the genital tract were CEA-negative, but the brushborder of normal colon was CEA-positive. CEA activity in tissue was found in 11 of 14 squamous cell carcinomas of the cervix (79%) and in 7 of 9 cervical adenocarcinomas (78%). By contrast, endometrial adenocarcinoma showed CEA staining in one of 11 tumors only, and in ovarian adenocarcinoma positive CEA staining was never seen. CEA reactions were sometimes found in benign mucinous cystadenomas of the ovary, but not in serous cysts. The serum CEA concentration was normal or sometimes slightly elevated in cases where the tumor was CEA-negative, whereas normal or even highly elevated serum CEA concentrations were seen in CEA-positive tumors. On the basis of these results the following conclusions can be made: 1) Serum CEA measurement is likely to be more effective in cervical and ovarian than in endometrial cancer for the detection of recurrent CEA-positive tumors. 2) It is possible by immunoperoxidase technique to identify certain CEA-positive cervical carcinomas before the serum CEA concentration becomes elevated. 3) Some benign ovarian tumors apparently produce high amounts of CEA without any clinical evidence of malignancy.

Immunoperoxidase staining of carcinoembryonic antigen in urinary bladder cancer

An immunoperoxidase study of the presence of carcinoembryonic antigen (CEA) in primary cancers of the urinary bladder, metastases to the bladder, non-malignant diseased bladder, and normal bladder tissues revealed that approximately 10 percent of the urothelial carcinomas (transitional cell and squamous cell types) contained detectable quantities of this antigen. The other tissues were devoid of stainable CEA. It thus appears that the incidence of positive CEA by immunoperoxidase staining of formalin-fixed, paraffin-embedded tumour tissue sections is much less than the frequency of blood or urinary CEA elevations in patients with urothelial cancer.

Early detection and prevention of carcinoma of the colon in patients with ulcerative colitis

Ulcerative colitis, particularly when there is total colonic involvement, is a premalignant lesion of the colon. We review the available methods for the early detection and prevention of colonic carcinoma in patients with ulcerative colitis. These methods include detection of precancer (carcinoma in situ) in rectal and colonic biopsies, with and without immunoperoxidase staining for carcinoembryonic antigen; detection of persistently elevated serum carci-noembryonic antigen; roentgenologic detection; colonoscopic detection; cytologic detection; and simple recommendation of total colectomy in all patients with continuously active, extensive colitis after 10 years of disease. Currently, of these methods available, only detection of precancer (carcinoma in situ) in rectal and colonic biopsies holds promise for the early detection of colonic carcinoma, and there are many pitfalls with this method. Precancer, when analyzed in total colectomies, is absent in 12% of patients with carcinoma complicating ulcerative colitis and is found in the rectum in only 66% of these patients. Thirteen percent of patients with severe ulcerative colitis requiring colectomy have precancer in the absence of cancer. Precancer, when analyzed in rectal biopsies of patients with ulcerative colitis, is found in 5.7% of the patients. Thirty-two percent (17/53) of those patients with precancer in rectal biopsy were found to have colonic carcinoma, while two-thirds of these patients did not have colonic cancer. The role of colonoscopy at regular intervals with the collection of multiple biopsies throughout the colon is currently being evaluated in hopes that this method will more accurately and consistently permit early detection of precancer and cancer in patients with ulcerative colitis of 10 or more years' duration.

The prognostic significance of carcinoembryonic antigen in the plasma and tumors of patients with endometrial adenocarcinoma

Carcinoembryonic antigen (CEA) levels in plasma and the immunocytochemical detection of tumor CEA were studied in patients with endometrial adenocarcinoma treated at the University of Kentucky Medical Center from 1973 to 1976. The incidence of CEA elevation in a group of 60 patients varied directly with uterine size, histologic differentiation, and stage of disease. Immunoperoxidase staining for CEA was performed on 42 specimens, and four were positive, indicating a tissue concentration of CEA of at least 5 μg per gram. Following operation, CEA levels returned to normal within eight weeks in all but two patients, both of whom were later shown to have persistent or recurrent cancer. These data suggest that serial plasma CEA determinations may be useful in predicting occult recurrence of endometrial cancer in patients in whom the plasma or tumor initially contains elevated concentrations of this antigen.

Carcinoembryonic antigen in histopathology: immunoperoxidase staining of conventional tissue sections.

A triple-bridge, indirect peroxidase-antiperoxidase method for demonstrating carcinoembryonic antigen (CEA) in frozen, ethanol-fixed or formalin-fixed, paraffin-embedded specimens was evaluated. Examination of 359 tissue specimens--234 malignant tumors, 37 benign neoplasms, 41 nonneoplastic diseased tissues, and 47 normal specimens--showed that CEA could usually be demonstrated in a group of cancers. We could detect CEA in carcinomas of the stomach, colon, rectum, pancreas, lung, and cervix. However, malignant tumors of the breast, prostate, kidney, larynx, brain, lymphoreticular system, soft tissues, and skin proved negative for CEA by the immunoperoxidase test. CEA could be detected in ethanol- or formalin-fixed sections. The only nonmalignant specimens showing CEA staining were a few benign tumors, the mucosae of some cases of colitis, and the resection margins of 2 cases of colon cancer; however, these were commonly very weak reactions. Measurement of tumor CEA content by radioimmunoassay revealed two causes for this relative specificity of the immunoperoxidase test for CEA:1) a quantitative difference existed in tissue CEA among the various specimens, and 2) the threshold for CEA staining in malignant specimens was usually above that in nonmalignant specimens. An analysis of the formalin-paraffin-treated sections showed that immunoperoxidase-tested CEA positivity reflected CEA levels in tissue of at least 3.0-5.0 mug/g; this permitted retrospective estimates of minimal tissue CEA concentrations in older histopathologic specimens by the immunoperoxidase reaction method. Formalin-paraffin-treated sections as old as 10 years still had demonstrable CEA. Although tumor CEA concentration correlated well with immunoperoxidase staining for CEA, plasma CEA titer did not necessarily reflect tumor CEA content. CEA positivity in primary and secondary tumors was strongly correlated; it was less strongly correlated with level of tumor differentiation.