Polyclonal Carcinoembryonic Antigen Research Articles

The value of polyclonal carcinoembryonic antigen immunostaining in the diagnosis of microvillous inclusion disease

Microvillous inclusion disease is a specific disorder recognized as a cause of intractable diarrhea of infancy. We studied three cases by light microscopy, electron microscopy, and immunostaining for polyclonal carcinoembryonic antigen (CEA). Histologically, all cases had villous atrophy and abnormal accumulation of periodic acid-Schiff-positive material in surface enterocytes. Ultrastructurally, poorly developed brush-border and intracytoplasmic inclusions lined by intact microvilli were present in surface enterocytes. Crypt cells showed well-preserved surface microvilli. Carcinoembryonic antigen immunostaining showed prominent intracytoplasmic reactivity in surface enterocytes and linear brush-border reactivity in crypt cells. Normal and diseased small bowel biopsy specimens used as controls revealed linear brush-border reactivity without intracytoplasmic staining. Intracytoplasmic positivity for carcinoembryonic antigen in microvillous inclusion disease is explained by its presence in the glycocalyx within the microvillous inclusions. The demonstration of a distinct staining pattern for polyclonal carcinoembryonic antigen in routinely processed small bowel biopsy specimens provides a new useful criterion that complements other established techniques for accurate diagnosis of microvillous inclusion disease.

A Case of Idiopathic Vulvar Calcinosis: The First in Japan

Idiopathic calcinosis of the scrotum is a rare condition of unknown etiology. As counterparts of this male disorder, only two female cases have been reported. We report a third case, the first of its kind, in Japan. Histochemical stains revealed acid mucopolysaccharide (acid-MPS) within the calcinosis and many infiltrated mast cells near it; these might histogenese the calcium deposition. Immunohistochemically, polyclonal carcinoembryonic antigen (CEA) and keratin stains revealed no positive cells near the calcium depositions.

Glassy Cell Features in Adenosquamous Carcinoma of the Uterine Cervix Histologic, Ultrastructural, Immunohistochemical, and Clinical Findings

Glassy cell features (GCF) were identified as composing a predominant pattern (more than 85% of histology) in six cases and a focal pattern (33-85% of histology) in 10 cases of a series of 53 adenocarcinomas (AC) and adenosquamous carcinomas (ADSQ) of the uterine cervix. In three cases examined ultrastructurally, GCFs correlated with many cytoplasmic polyribosomes and abundant rough endoplasmic reticulum, but Golgi complexes and tonofilaments were scant and intracytoplasmic lumina were absent. Intracellular mucin was present in the areas showing GCFs of four ADSQs with predominant GCFs and six ADSQs with focal GCFs. Two of three cases examined ultrastructurally showed intracellular electron-dense material that corresponded to mucin secretory material. Immunohistochemical studies of the six ADSQs with predominant GCF cases showed the following pattern of reactivity: monoclonal carcinoembryonic antigen (CEA), 2 of 6 cases; polyclonal CEA, 3 of 6; CA 125, 0 of 6; CA 19-9, 0 of 6; placental alkaline phosphatase, 0 of 6; and vimentin, 1 of 6. Focal GCF areas showed monoclonal CEA, 4 of 9 cases; polyclonal CEA, 3 of 9; vimentin, 4 of 9; while CA 125, CA 19-9, and placental alkaline phosphatase were negative in areas of GCFs. One of three patients with ADSQ with predominant GCFs and five of nine patients with ADSQ with focal GCFs with at least 1 year of follow-up were disease free. No association between GCFs (combined focal and predominant) and recurrent disease was present when compared to the other 29 AC and ADSQ patients with follow-up. Recurrent disease in our series of AC and ADSQ was only associated with stage III or IV disease at presentation (P less than 0.001). There was no association with adenosquamous histology, histologic grade, lymphatic invasion, or age. There were insufficient cases of ADSQ with predominant GCFs with follow-up to evaluate fully prognostic significance of this subgroup. Our study suggests that GCFs are part of the spectrum of differentiation in ADSQ of the cervix rather than a distinct histologic type of carcinoma with unique clinical significance.

Symptomatic C-cell Hyperplasia Associated With Chronic Lymphocytic Thyroiditis

A 58-year-old euthyroid man with episodic flushing and a 2-year history of progressive wheezing was found to have a hypoechoic lesion in one lobe of his thyroid and hypercalcitoninemia in response to pentagastrin stimulation. Thyroidectomy revealed bilateral C-cell hyperplasia unexpectedly associated with chronic lymphocytic thyroiditis. The C-cells exhibited positive immunohistochemical staining for calcitonin and polyclonal carcinoembryonic antigen (CEA). Postoperatively, the wheezing and flushing subsided and the serum calcitonin level was not elevated with pentagastrin stimulation. The substance or substances responsible for the wheezing and flushing were not specifically identified. Nine other specimens of chronic lymphocytic thyroiditis were examined for C-cell hyperplasia and two had small hyperplastic foci, but of a lesser degree than the index case. These patients did not exhibit wheezing and flushing. The development of C-cell hyperplasia in chronic lymphocytic thyroiditis is uncommon and the mechanism for its occurrence is unexplained. This patient appears to be the first reported case of symptomatic C-cell hyperplasia associated with chronic lymphocytic thyroiditis. The substance or substances responsible for the clinical symptoms remain to be identified.

Homogeneous penetration but heterogeneous binding of antibodies to carcinoembryonic antigen in human colon carcinoma HT-29 spheroids.

The monoclonal antibodies 38S1, directed against the carcinoembryonic antigen (CEA), were tested for penetration and binding in human colon carcinoma HT-29 spheroids. Penetration was studied with a method which has not previously been used in immunological investigations. The method, which allows unbound substances to be visualized, is based on freeze drying, vapour fixation, dry sectioning and dry autoradiography. The antibodies penetrated easily and all parts of the HT-29 spheroids seemed to be reached within 15 min. The penetration was even faster than in control glioma U-118MG spheroids that did not express CEA. Binding of the 38S1 antibodies was demonstrated after processing with conventional histology and autoradiography. The binding in the HT-29 spheroids was, after a 1-h incubation period, extremely heterogeneous and occurred mainly in the peripheral parts. More cells were binding the antibodies after 8-h and 32-h incubations and these cells were arranged in peripheral clusters. No binding at all was seen in the CEA-negative glioma spheroids. The distribution of CEA antigens in monolayers and in frozen sections of spheroids of HT-29 cells was analysed with immunohistochemical staining using polyclonal CEA antibodies. The CEA antigens were heterogeneously distributed in both spheroids and monolayers and were as heterogenous as the binding of the monoclonal antibodies in the living spheroids. Thus, the heterogeneous binding in the living spheroids was not due to penetration barriers, but instead to the heterogeneity in the CEA antigen expression.

Immunocytochemical reactivity of breast cancer tissue with antibodies to neuron-specific enolase and an adenocarcinoma-associated glycolipid antigen

The immunocytochemical reactivity of breast cancers to antibodies raised against neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and an adenocarcinoma-associated glycolipid antigen (IR-14) was studied in relation to the long-term outcome of the neoplastic disease. The patients whose tumours exhibited reactivity with the IR-14 and anti-NSE antibodies had a considerably better 5-year and long-term survival than those without such reactivity. Assessment of DNA-ploidy of the tumour cells was also relevant for long-term prognosis, immunohistochemistry giving additional prognostic information among aneuploid tumours. Reactivity with polyclonal CEA antibodies was of no prognostic value. It is suggested that tumours carrying the IR-14 reactive epitope, which was originally isolated from circulating antigen-antibody complexes, might evoke a favourable immune response and thus improve the survival of the patient.

Carcinoembryonic Antigen and Nonspecific Cross-Reacting Antigen in Thyroid Cancer An Immunocytochemical Study Using Polyclonal and Monoclonal Antibodies

The expression of carcinoembryonic antigen (CEA) and related antigens in formalin-fixed paraffin-embedded tissues of 200 primary thyroid carcinomas and 22 nonmalignant thyroid lesions was studied immunocytochemically by using three monoclonal antibodies recognizing different epitopes on CEA and related antigens. The monoclonal antibody 431/31 defined epitope (present only on CEA) was found exclusively on 77% of the medullary thyroid carcinomas and on 100% of hyperplastic C-cell nodules adjacent to infiltrating C-cell carcinomas. The monoclonal antibodies 374/14 and 250/183, defining epitopes present on CEA and the nonspecific cross-reacting antigens 95 or 55, reacted with 88% and 82%, respectively, of the medullary carcinomas, but labelled also many nonmedullary thyroid carcinomas (follicular 34% and 18%, papillary 42% and 30%, anaplastic 18% and 13%), follicular adenomas, and nonneoplastic follicle-cell lesions. Similar results were obtained by using a polyclonal CEA antiserum preabsorbed with lyophilized spleen tissue. The findings suggest that nonspecific cross-reacting antigens can be expressed by all types of thyroid carcinoma, while CEA is present only in C-cell tumors of this organ.