Positive Staining For Carcinoembryonic Antigen Research Articles

Hypertrophic plaques on the vulva

An otherwise healthy woman in her 40s presented with a 2-year history of itching of the vulva. She had been diagnosed with dermatitis and prescribed topical corticosteroids, but to little effect. She denied high-risk sexual contacts or exposure to potential contact allergens. Physical examination revealed well-demarcated white-red and hypertrophic plaques, with scattered dotlike erosions. As shown in Figure 1, vulvar skin changes were visualized as the patient retracted the surrounding tissues. Histopathologic examination revealed a proliferation of Paget cells within the surface squamous epithelium (Figure 2), with the Paget cells displaying positive staining for carcinoembryonic antigen and cytokeratin (CK) 7, and negative staining for AE1/AE3, CK20, and melan-A.

Relations of carcinoembryonic antigen (CEA) staining of cancer tissue and serum CEA levels to histologic response in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemoradiotherapy (nCRT).

790 Background: Neoadjuvant chemoradiotherapy (nCRT) is a standard of care for LARC. The serum CEA level is a predictor of the response to nCRT; however, the relation between CEA production immunohistochemically evaluated in cancer tissue and treatment response remains unclear. Methods: The study group comprised 145 patients with clinical Stage II/III rectal cancer who received nCRT followed by surgery from 2005 through 2013. The radiation dose was 40 to 45 Gy. UFT- or S-1-based chemotherapy was given concurrently. Surgery was performed 6 to 8 weeks after the completion of radiotherapy. Immunohistological CEA staining patterns in biopsy tissue obtained before nCRT were evaluated. Specimens in which the luminal cell membrane or the cytoplasm was strongly stained were defined as staining positive. The histologic response was evaluated on the basis of the pathological complete response (ypCR) rate, T downstaging, tumor regression grade (TRG), and tumor shrinkage rate on MRI. Results: CEA staining in biopsy specimens and serum CEA levels were both negative in 17 patients (11.7%) and both positive in 72 patients (49.7%). There was no relation between the groups (p = 0.174). In patients with negative CEA staining, the rates of ypCR, T downstaging, marked regression, and mean tumor shrinkage were 24.3%, 51.4%, 45.9%, and 72.3%, respectively. In patients with positive CEA staining, these rates were 11.1%, 48.1%, 37.0%, and 72.8%, respectively. CEA staining of cancer tissue was not significantly related to the ypCR rate, T downstaging, a marked regression rate, or the tumor shrinkage rate on MRI (p = 0.060, p = 0.849, p = 0.436, and p = 0.874, respectively). Patients with negative serum CEA levels before nCRT had significantly higher rates of ypCR, T downstaging, marked regression, and tumor shrinkage on MRI than did patients with positive serum CEA levels (p = 0.014, p = 0.006, p = 0.002, and p = 0.014, respectively). Conclusions: Serum CEA levels before nCRT were a significant predictor of the histologic response to nCRT; in contrast, tissue CEA staining before nCRT was unrelated to the histologic response to nCRT.

Relation between carcinoembryonic antigen (CEA) production in colorectal cancer (CRC) tissue and serum CEA levels: Comparison between the time of recurrence and initial diagnosis.

561 Background: Because serum CEA often becomes positive before the diagnosis of recurrence, CEA is widely used for postoperative surveillance. Serum CEA is negative at initial diagnosis as well as at recurrence in some patients. We examined the relation between serum CEA levels and tissue CEA staining status both at initial surgery and at recurrence. Methods: Between 1998 to 2012, 1,306 patients (pts) with colon cancer (CC) underwent curative resection. Serum CEA levels were measured at initial surgery and at recurrence and immunohistochemical staining for CEA in primary and metastatic lesions was performed in 46 pts. Serum CEA levels of 10ng/mL or more were regarded as positive. Results: Serum CEA were positive in 17 pts (37%) at initial surgery and in 20 (43%) at recurrence. CEA staining was positive in primary lesions in 24 pts (52%) and metastatic lesions in 33 (72%). The positive rate was higher in metastatic lesions (p=0.053). Among pts in whom serum CEA was positive at initial surgery, CEA staining in primary lesion was positive in 12 pts (71%) and negative in 5 (29%). Among pts in whom serum CEA was negative, CEA staining in primary lesion was positive in 12 pts (41%) and negative in 17 (59%). Serum CEA at initial surgery was not related to CEA staining in primary lesion(p=0.0722). Among pts positive for serum CEA at recurrence, CEA staining in metastatic lesions was positive in 19 pts(95%) and negative in 1(5%). Among pts negative for CEA at recurrence, CEA staining in metastatic lesions was positive in 14 pts (54%) and negative in 12 (46%). Serum CEA at recurrence was significantly related to CEA staining in metastatic lesions (p=0.0026). Among 33 pts in whom CEA staining was positive at recurrence, serum CEA was negative in 14 (42%). Conclusions: In pts with recurrence of CC, there was no relation between the staining CEA status and serum CEA level at initial diagnosis. In contrast, these variables were significantly related at recurrence. However, 42% of pts with positive staining for CEA in metastatic lesions had negative serum CEA levels. Our findings suggest that factors besides the production of CEA by cancer cells are related to serum CEA levels.

Metastatic Medullary Thyroid Cancer Presenting with Elevated Levels of CA 19-9 and CA 125

Calcitonin and carcinoembryonic antigen (CEA) are established markers of medullary thyroid cancer (MTC), used in the diagnosis and monitoring of disease and its progression. In clinical practice, various other tumor markers are utilized in the follow-up of different malignancies, although their utility has not been well described in MTC. CA 19-9 antigen, routinely used in the monitoring of pancreatic cancer, also has been detected in the tissue of approximately 6% of MTCs. However, its presence has never been reported in the serum of these patients. Elevation of CA 125 antigen, utilized as a tumor marker for ovarian cancer, has never been reported in MTC. We report a novel finding of metastatic MTC presenting with elevated CA 19-9 and CA 125 serum levels, with concurrent tissue staining for these antigens. A 56-year-old woman with multiple endocrine neoplasia 2B syndrome, post subtotal thyroidectomy for MTC in childhood, presented with extensive metastatic spread of MTC to the lungs and liver, 47 years after the original diagnosis. The patient's calcitonin level decreased from 2950 to 261 pg/mL (reference range: <20 pg/mL) over a 20-year period. The serum CEA level was elevated at 6800 ng/mL (reference range: <5.1 ng/mL). Because of a concern for an alternate malignancy, serum CA 19-9 and CA 125 tumor markers were measured and found to be significantly elevated, at 39,334 U/mL (reference range: <35.1 U/mL) and 96.2 U/mL (reference range: 7-41 U/mL), respectively. Immunostaining of the metastatic MTC tissue showed patchy staining for calcitonin, strongly positive staining for CEA and CA 19-9, and weakly positive staining for CA 125. Drawing from experience with CA 19-9 and CA 125 tumor markers in other malignancies, we propose that they may be associated with aggressive forms of MTC with significant metastatic potential.

Female para‐urethral adenocarcinoma: Histological and immunohistochemical study

Female urethral cancer with a diverticular form is assumed to originate from the para-urethral duct, which is embryologically homologous to the male prostate gland. The purpose of the present paper was to investigate the female para-urethral adenocarcinomas histologically and immunohistochemically. Surgical specimens obtained from six female patients with para-urethral adenocarcinomas were examined histologically, and an immunohistochemical study using antibodies against carcinoembryonic antigen (CEA), prostate specific antigen (PSA), and chromogranin A was performed. On histologic examination, the female para-urethral cancers were divided into five cases of mucin-producing-type adenocarcinoma and one case of clear cell-type adenocarcinoma. All five mucin-producing-type adenocarcinomas were positive with anti-CEA, and two of them showed neuroendicrine differentiation. One of them showed a focally positive area with anti-PSA. The clear cell-type adenocarcinoma had no positive reactions to these antibodies. On the basis of histologic structure, positive CEA staining, and the presence of focal neuroendocrine differentiation, mucin-producing-type adenocarcinomas may arise from the proximal part of the para-urethral duct.

Gamma-amino-butyric acid immunoreactivity in intramucosal colonic tumors.

The level of gamma-amino-butyric acid (GABA) is reported to be increased in colon cancer. Moreover, data suggests that GABA plays a role in the proliferation or maturation of some types of cells. We examined the expression of GABA in intramucosal colonic tumors to clarify the relation between GABA and the degree of atypia. Paraffin sections were prepared from 56 protruded-type colonic neoplasms, which were classified as intramucosal adenocarcinoma (AC), adenoma with severe atypia (ASA), or adenoma with mild to moderate atypia (AMA). Expression of GABA was investigated immunohistochemically, and GABA immunoreactivity was compared to the staining patterns of carcinoembryonic antigen (CEA) and cancer-associated antigen (CA19-9) which were classified into three categories. Intense GABA immunoreactivity was observed in 73.7%, 54.6%, 13.3%, and 5.4% of AC, ASA, AMA, and normal mucosa specimens, respectively. Kendall's correlation coefficient between GABA immunoreactivity and the degree of atypia was 0.447. Strong, positive CEA staining (pattern 3) was observed in 57.9%, 36.3%, and 13.3% of AC, ASA, and AMA specimens, respectively. Strong, positive CA19-9 staining was observed: 26.3%, 9.1% and 0%, respectively. In AC and ASA, the proportion of glands with strong GABA immunoreactivity was greater than the proportion of glands that were strongly positive for CA19-9. GABA may be useful as a tumor marker in combination with other tumor markers such as CEA and CA19-9.

Gastrointestinal metastasis to the breast

Background. Although primary breast cancer is common, metastatic disease to the breast, especially primary gastrointestinal cancer, is rare. Routine pathologic examination may be helpful in determining the true diagnosis, but can be misleading. Methods. To determine whether a signet ring carcinoma was a primary malignancy of the gastrointestinal tract metastatic to the breast or vice versa, histochemical analysis was performed for Her-2/NEU, gross cystic disease fluid protein-15, estrogen receptor, progesterone, carcinoembryonic antigen, cytokeratin 7, and cytokeratin 20. Results. Positive staining for carcinoembryonic antigen and cytokeratin 20 (and negative staining for the breast cancer antigens), and the clinical criteria favors the diagnosis of gastrointestinal carcinoma metastatic to the mammary gland. Conclusions. Because the prognosis of therapy for metastatic cancer to the breast differs from that of primary breast cancer, it is imperative that the correct diagnosis be established. Immunohistochemistry for carcinoembryonic antigen and cytokeratin 20 are particularly useful. Metastatic gastrointestinal carcinoma to the breast is a rare lesion but needs to be at least included in the differential diagnosis of breast masses, especially in patients with a history of gastrointestinal cancer. (Surgery 2002;132:889-93.)

Cea tissue staining in colorectal cancer patients - correlation with plasma cea, histology and staging

To study the expression of tissue carcinoembryonic antigen (CEA) by immunoperoxidase staining in colorectal adenocarcinomas and its relation with preoperative serum CEA and clinicopathological parameters, we studied 85 unselected patients who underwent resective surgery for colorectal adenocarcinomas and were followed up for a mean of 66 mths. All tumors except 2 showed positive staining for CEA. The staining pattern was classifiable into 4 types: apical, cytoplasmic, basolateral and stromal, according to the predominant sites of staining. We found a significant positive correlation between tissue CEA staining pattern and preoperative plasma CEA. Plasma CEA levels were higher when tumor cell staining extended to basolateral regions of the cells and into stromal tissues rather than restricted to apical and cytoplasmic regions (p = 0.012). Furthermore, tissue CEA staining also correlated positively with vascular invasion by tumor cells (p = 0.046), with basolateral and stromal types associated with more frequent vascular invasion than apical and cytoplasmic types. This was in contrast to the preoperative CEA which did not correlate with vascular permeation. We speculate that tissue CEA staining is useful in indicating possible vascular invasion even at early stage whereas vascular invasion by a larger tumor bulk or even tumor metastases may be necessary to produce an increased plasma CEA level that is detectable. On the other hand, preoperative plasma CEA had a strong, positive relationship with tumor stage and mortality (p < 0.001 for both). Preoperative CEA was higher in tumors showing moderate and poor differentiation, although it did not reach statistical significance (p = 0.068), whereas tissue CEA staining had no correlation with tumor differention.(ABSTRACT TRUNCATED AT 250 WORDS)

Squamous cell carcinoma of ureter extending into renal vein Positive immunohistochemical staining for carcinoembryonic Antigen

A case of squamous cell carcinoma of the ureter with extension into the renal vein is presented. Immunoperoxidase method revealed positive staining for carcinoembryonic antigen. The literature on ureteral tumors is reviewed with special reference to renal vein involvement and carcinoembryonic antigen.

Immunohistochemical Localization of Carcinoembryonic Antigen(CEA) in Squamous Cell Carcinoma of the Uterine Cervix: Prognostic Significance of Localization Pattern of CEA.

Immunohistochemical localization of carcinoembryonic antigen (CEA) was investigated with 100 cases of invasive squamous cell carcinoma of the uterine cervix in order to evaluate the relationship of the positive pattern of CEA to the prognoses of patients with this neoplasm. Positive staining for CEA using peroxidase-antiperoxidase method was noticed in all tumors studied. The localization patterns of CEA were divided into the following four types depending on the location of CEA-positive areas in cancer nests: central type, surrounding type, diffuse type, and focal type. Survival curves based on calculation by the method of Kaplan-Meier showed that prognosis of patient was most excellent in the disease of central type, which was followed by surrounding type, diffuse type, and focal type, in this order. The survival curve for central type was significantly better than those for diffuse type and focal type (p less than 0.05) as assessed by Log rank test. In squamous cell carcinoma of the cervix, consequently, prognosis of patient might be favorable when CEA is demonstrated in the center part of cancer nests by an immunohistochemical technique.

Lung Carcinoma Metastatic to Microfollicular Adenoma of the Thyroid A Case Report

A 75-year-old woman with lung adenocarcinoma in whom autopsy revealed metastasis to microfollicular adenoma of the thyroid is described. A thyroid tumor specimen from this patient was initially interpreted as representing primary encapsulated follicular carcinoma of the thyroid associated with a component of poorly differentiated carcinoma of follicular cell origin. The widespread involvement of the lungs and other sites was also interpreted as metastases from the poorly differentiated carcinoma component within the encapsulated follicular carcinoma of the thyroid. Subsequent meticulous histologic examination revealed that the thyroid tumor was a microfollicular adenoma, and that the component of poorly differentiated carcinoma within it was the same as the lung carcinoma. Immunohistochemical investigation revealed that the poorly differentiated carcinoma cells within the thyroid tumor were stained positively with polyclonal and monoclonal antibodies against carcinoembryonic antigen (CEA) and negative for thyroglobulin and calcitonin. The carcinoma cells from the lungs and other sites also showed positive staining for CEA. These findings support the view that the component of poorly differentiated carcinoma was a metastatic lesion from the primary lung carcinoma to the microfollicular adenoma of the thyroid. The present study emphasizes that attention should be directed to thyroid metastasis, even if it is within a thyroid primary neoplasm.

Clear cell hidradenoma with whorl formation of squamoid cells: Immunohistochemical and electron microscopic studies

Many groups of squamoid cells arranged in whorls were found in a case of clear cell hidradenoma. These cells showed positive staining for carcinoembryonic antigen, but S-100 protein was not detected. Electron microscopic examination showed considerable amounts of tonofilarnents, but neither keratohyalin granules nor multivesicular dense bodies were present in these cells. These features suggest that the constituting cells of whorls differentiated toward the eccrine ductal cells, in particular the intraepidermal ductal cells.

Well-Differentiated Cholangiocarcinoma

In order to provide useful criteria for the histologic diagnosis of well-differentiated cholangiocarcinoma, we reviewed 62 cases of this type. We assessed the incidences of various cytological as well as structural atypia, positive staining for carcinoembryonic antigen, secretory component, or carbohydrate antigen 19-9. We also assessed alterations in mucin production in comparison with noncancerous bile duct epithelium (48 cases). Using a computer-assisted multivariate analysis, three indicators--including nuclear size variation, formation of a second gland (distended intracytoplasmic lumina or focal cribriform pattern), and positive reaction in carcinoembryonic antigen--were shown to be the most important histologic parameters for the diagnosis of cholangiocarcinoma. One of the three indicators was occasionally positive in noncancerous bile ducts, but two or three indicators were only found in cholangiocarcinoma (p less than 0.001). The majority of the cases of cholangiocarcinoma were indeed positive for two or three of these criteria (54/62; 87%). Among other atypical changes, irregular nuclear configurations, mitosis, and prominent nucleoli showed a high specificity for cholangiocarcinoma. In addition to the major criteria, combined application of these factors can also be helpful for the actual histologic assessment.

Characterization of cell types in human breast tumor primary cultures

Primary cultures of cells from breast carcinomas were attempted in 74 cases. Growth was observed in 46 cases. Using immunochemical demonstration of keratin proteins (KER), epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), three morphologically distinct cell populations were characterized and described. Two cell types (E- and E'-cells) were identified as epithelial by their positive staining for KER and EMA. The third type (F cells) displayed a negative staining for these two epithelial markers; they were considered as stromal cells (fibroblasts). More than 50% of the cultures consisted of pure epithelial cells. Positive CEA staining was observed only in KER- and EMA-positive cells. Out of the 30 cultures, 15 displayed positive staining for CEA. In 7 of these, 30-50% of cells displayed positive, diffuse staining for CEA. The other 8 cultures consisted of more than 50% CEA-positive cells. Strong and homogeneous positivity was restricted to the E-cells, while in the same cultures, E'-cells displayed heterogeneous and diffuse staining. Efficiency and value of this cell culture system are discussed, in comparison with other human breast tumor cell (HBTC) culture techniques. Identification of growing cells and cellular composition of primary cultures are emphasized.

Carcinoembryonic antigen in mucoceles of oral mucosa

Immunohistochemical detection of carcinoembryonic antigen (CEA) was reported in mucocele and associated minor salivary glands of oral mucosa. Higher levels of staining for CEA occurred in salivary glands with attached mucoceles, in which acinar cells and ductal segments in the gland displayed concentrations of CEA higher than those in normal minor salivary glands. Floating cells also gave positive CEA staining, whereas epithelial fragments and connective tissue in the mucocele wall were lacking in CEA. It was suggested that mucoceles in oral mucosa accumulated CEA in associated minor salivary glands.

Secretory Meningioma

Six meningiomas with abundant hyaline inclusions (pseudopsammoma bodies) were studied. As seen by light and electron microscopy, hyaline inclusions are composed of material of varying structures located in intracellular lumina lined by microvilli. A remarkable pericytic proliferation within the vessel walls was found in five cases. In all six cases, immunohistochemical examination for multiple antigens showed positive staining for carcinoembryonic antigen and epithelial membrane antigen in inclusions and surrounding cells. Weak positivity was found for keratin and secretory component in five cases and for alpha-1-antitrypsin and IgM in four cases. It is concluded that secretory meningioma is a distinct type of meningioma, usually meningothelial in type. It shows characteristic light-microscopic, ultrastructural, and immunohistochemical features of epithelial and secretory differentiation with accumulation of secretory material in the form of hyaline inclusions; marked vascular pericytic proliferation is also frequently present.

Epithelial markers in primary skin cancer: an immunoperoxidase study of the distribution of epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA) in 65 primary skin carcinomas.

Sixty-five primary malignant skin tumours have been stained for carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) using rabbit polyclonal affinity-purified antibodies and an indirect immunoperoxidase technique. The tumours consisted of 15 invasive squamous carcinomas, 23 basal cell carcinomas, 16 malignant eccrine poromas (porocarcinomas), and 11 sebaceous carcinomas. The basal cell carcinomas were negative for CEA and EMA except where there was keratotic or sebaceous differentiation. All the sebaceous and squamous carcinomas and 15/16 porocarcinomas contained EMA. 12/15 squamous carcinomas were positive for CEA. The malignant poromas were negative for CEA except on the ulcerated surface of two. In tumours classified as sebaceous carcinomas there was positive staining for CEA in some cells, cyst contents and/or keratotic foci. These findings have implications for the use of immunoperoxidase localization of epithelial markers in the differential diagnosis of primary and metastatic skin cancer.

Calcitonin and Carcinoembryonic Antigen as Tumor Markers in Medullary Thyroid Carcinoma

DeLellis, Ronald A., Rule, Allyn H., Spiler, Ira, Nathanson, Larry, Tashjian, Armen H., Jr., and Wolfe, Hubert J.: Calcitonin and carcinoembryonic antigen as tumor markers in medullary thyroid carcinoma. Am J Clin Pathol 70: 587–594, 1978. Six patients with locally advanced and/or metastatic medullary thyroid carcinoma, of both familial and non-familial types, had markedly elevated serum concentrations of calcitonin and carcinoembryonic antigen (CEA). The highest serum CEA concentrations were found in those patients with the most extensive disease and correlated with the extent of serum calcitonin elevation. Immunocytochemical studies revealed positive staining for CEA and calcitonin in tumor cells, and these results were confirmed by correlative radioimmunoassays of tumor extracts for CEA. Patterns of calcitonin and CEA immunoreactivity in tissue sections were similar but not identical. While most tumor cells contained both CEA and calcitonin, some groups of tumor cells that were strongly stained for calcitonin did not stain for CEA. In contrast to the granular staining pattern for calcitonin, CEA immunoreactivity tended to be diffusely distributed throughout the cytoplasm or was concentrated at the plasma membranes. Normal and hyperplastic C cells, on the other hand, showed strong staining for calcitonin but did not contain immunoreactive CEA. It is concluded that CEA is a useful tumor marker in patients with locally advanced or metastatic medullary thyroid carcinoma and that CEA and calcitonin can be produced by the same neoplastic cell populations.

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.