Positive Carcinoembryonic Antigen Research Articles

Prospective validation of quantitative CEA mRNA detection in peritoneal washes in gastric carcinoma patients

Prediction of peritoneal relapse is extremely important for gastric cancer patients after curative surgery. The present study prospectively validates the prognostic ability of quantifying carcinoembryonic antigen (CEA) mRNA in peritoneal washes by real-time reverse transcriptase–polymerase chain reaction. Based on a retrospective study of 197 curatively resected gastric cancer patients (training set), we determined a cutoff value of CEA mRNA using receiver-operating characteristic curve. We used this cutoff value to validate the risk of peritoneal recurrence in a new cohort of 86 gastric cancer patients (validation set) between July 2000 and December 2002 in a prospective study. During the median 30 months of postoperative surveillance, 20 of the 86 patients died, and 13 of the 20 developed peritoneal metastases. Peritoneal recurrence-free survival as well as overall survival was significantly worse in patients with positive CEA mRNA (P<0.0001). Multivariate analysis with the Cox proportional hazards model showed that positive CEA mRNA was a significant independent risk factor with both survival (P=0.0130) and peritoneal recurrence-free survival (P=0.0006) as end points. These results indicate that quantitation of CEA mRNA in peritoneal washes is a reliable prognostic indicator of peritoneal recurrence in the clinical setting.

Phenotypic diversity of intrahepatic and extrahepatic cholangiocarcinoma on aspiration cytology and core needle biopsy

Cholangiocarcinoma (CC) represents approximately 10% of primary liver malignancies and can mimic metastatic adenocarcinoma. The authors retrospectively reviewed the cytopathology files at the University of Texas Medical Branch to identify patients who were diagnosed with intrahepatic or extrahepatic CC by aspiration cytology between 1995 and 2004. Brush cytology specimens of extrahepatic CC were excluded. All diagnoses were confirmed as CC by clinical, imaging, and histopathologic findings and by chart review. Cytopathology files from 13 patients with CC diagnosed by FNA were retrieved. The male:female ratio was 5:8, and the patients ranged in age from 29 years to 74 years (mean age, 59 years). In 12 of 13 patients, aspirates were obtained by ultrasound guidance; and, in 1 patient, computed tomography guidance was used. Three patients had aspirates only, 10 patients also had core biopsies, and 1 patient had cell block preparations. The phenotypic distribution of CC according to the World Health Organization (WHO) histologic classification was 9 adenocarcinoma (intrahepatic), not otherwise specified (NOS) (69%); 2 gastric foveolar type (extrahepatic) CCs (15%); 1 intestinal type (extrahepatic) CC (8%); and 1 sarcomatous/spindle cell type (intrahepatic) CC (8%). One adenocarcinoma, NOS was well differentiated CC with bland tubular architecture, and one was pleomorphic. Ancillary histochemical and immunochemical stains were performed on 5 of 13 specimens, which included 4 core biopsies and 1 aspirate with Mucicarmine positivity (3 specimens), carcinoembryonic antigen positivity (3 specimens), and a cytokeratin 7 (CK7)-positive/CK20-negative pattern (2 specimens). The 1 sarcomatous/spindle cell type CC was chromogranin-negative and low molecular weight keratin (cell adhesion molecule 5.2)-positive, which excluded metastatic carcinoid. Classification of intrahepatic and extrahepatic CC in aspiration cytology specimens was achieved in a reliable manner concordant with the WHO histologic classification. Special types of CC with bland nuclear features posed a diagnostic challenge on cytologic evaluation, particularly the well differentiated CC with tubular architecture and the gastric foveolar type CC with mucin-producing tumor cells. The addition of core biopsy and/or ancillary studies, such as histochemical and immunochemical stains, were helpful in reaching the correct diagnosis.

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.

Tumour-associated trypsin inhibitor, carcinoembryonic antigen and acute-phase reactant proteins CRP and α1-antitrypsin in patients with gastrointestinal malignancies

Objectives: Elevated serum tumour-associated trypsin inhibitor (TATI) levels have been observed in association with malignancy or inflammation. The aim of our study was to evaluate the role of TATI in gastric and colorectal cancer. Design and methods: In preoperative serum samples, we measured TATI, carcinoembryonic antigen (CEA), C-reactive protein (CRP) and α 1-antitrypsin (AAT). Results: Elevated levels of TATI were observed in 50% and 41.7% of patients with gastric and colorectal cancer. Elevated levels of TATI were observed only in 8% of patients with benign gastrointestinal malignancies (92% specificity). Elevated levels of CEA were observed in 25% and 24.4% of patients, respectively. The total positivity of CEA and TATI (with at least one marker positive) was 62.5% and 57%, respectively. Spearman's test has shown a statistically significant correlation among serum TATI, CRP and AAT levels ( P < 0.01). Conclusions: In gastrointestinal cancer, TATI can be used as a complementary tumour marker in addition to CEA. Regulation of TATI synthesis resembles that of acute-phase reactant proteins.

Comparison of immunohistochemistry and real-time reverse transcription-polymerase chain reaction to detect expression of carcinoembryonic antigen in lung cancer

Real-time reverse transcription-polymerase chain reaction (RT-PCR) can detect mRNA of carcinoembryonic antigen (CEA) quantitatively. We compared the serum concentration, localization, and mRNA expression of CEA to determine the relationship between these three factors in patients with lung cancer. Tumors from ten patients who underwent surgery were analyzed. The serum concentration of CEA was measured before initiating therapy using a quantitative latex agglutination reaction. Immunohistochemical staining of pathologic specimens of resected tumors was performed to localize CEA. Real-time RT-PCR to detect mRNA of CEA was performed for isolating RNA from a piece of fresh-frozen tumor. Positivity for CEA production was 20% for serum, 60% for immunohistochemistry, and 80% for real-time RT-PCR. Thus, the percentage of mRNA and protein positivity of CEA in lung cancer was much higher than for the serum CEA concentration. No statistically significant correlation between the serum CEA concentration and the amount of mRNA expression was found (p=0.0932). Real-time RT-PCR is useful to quantify specific mRNA expression from a small piece of tissue.

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.

Significance of Follow-up Examination of Tumor Markers after a Radical Gastrectomy in Gastric- cancer Patients

Purpose: The prognostic significance of peri-operative serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 determination in patients with gastric cancer has been controversial. This study was performed to evaluate the significance of CEA and CA19-9 as clinical predictors of prognosis. Materials and Methods: The correlations between peri-operative serum CEA/CA19-9 levels and clinicopathologic factors were evaluated retrospectively in gastric cancer patients who had undergone curative surgery during the period from January 1995 to December 1998 at the Department of Surgery, Yonsei University College of Medicine. Results: The positive rates for CEA and CA19-9 were and , respectively. The CEA positivity was related to the depth of invasion (P=0.040), lymph-node metastasis (P=0.000), and stage (P=0.001). The CA19-9 positivity was significantly related to the depth of invasion (P=0.000), lymph-node status (P=0.000), and stage (P=0.000). The positive rate of combined assay of pre-operative CEA and CA19-9 was There were statistically significant correlations with stage, depth of invasion, or degree of lymphnode metastasis in the combined assay. The survival rates according to the positivity of CEA and to the positivity of CA19-9 were clearly different (P=0.000). Conclusion: It should be stressed that even a simple blood test prior to surgery could be useful in establishing the depth of invasion, the status of lymph-node involvement, and the prognosis. For improved survival, an aggressive lymphadenectomy and adjuvant chemotherapy should be considered for patients with positive levels of pre-operative CA19- 9.

Quantitative detection of CEA expressing free tumor cells in the peripheral blood of colorectal cancer patients during surgery with real-time RT-PCR on a LightCycler

We applied novel real-time reverse transcriptase-polymerase chain reaction (RT-PCR) with a LightCycler for quantitative detection of carcinoembryonic antigen (CEA) mRNA expressing tumor cells in the peripheral blood of colorectal cancer patients. Analysis of peripheral blood samples from 99 potentially curative colorectal cancer patients revealed a significantly higher mean CEA mRNA value in post-operative bloods (18.71) than in pre-operative blood (1.03) (P=0.003). Kaplan–Meier analysis demonstrated disease free survival of patients with positive CEA mRNA in post-operative blood to be significantly shorter than in cases negative for CEA mRNA (P=0.03). These results suggest that tumor cells could be shed into the bloodstream during surgical procedures, and these free tumor cells are accompanied by a poor patient outcome. Real-time quantitative RT-PCR is a useful technique for quantitative assessment of free tumor cells in the peripheral blood of colorectal cancer patients.

Pathological and Immunohistochemical Studies of Choroid Plexus Carcinoma of the Dog

Choroid plexus carcinomas in four dogs (three male, one female) aged 2·5 to 10 years, were examined by light microscopy and immunohistochemistry. The dogs showed progressive neurological signs including ataxia, seizures, vestibular disease and cranial nerve deficits, lasting for several months in some cases. Primary tumours were localized in the lateral (one case), third (one case), and fourth (two cases) ventricles. Hydrocephalus was evident at post-mortem examination in one case. In two cases the neoplastic cells closely resembled the structure of normal choroid plexus, with a distinct papillary pattern, composed of well-differentiated columnar epithelium. In the other two cases, cellular pleomorphism, nuclear atypia, increased mitotic activity and necrosis were observed. In all cases, dissemination of neoplastic cell clusters was detected within the subarachnoid space or the ventricular cavity. Immunohistochemical examination showed a multifocal labelling pattern for pankeratin and cytokeratin AE1 and diffuse vimentin positivity in poorly differentiated tumours. Well-differentiated choroid plexus carcinomas showed multifocal immunoreactivity for cytokeratin AE3, multifocal to diffuse immunoreactivity for vimentin and occasional positivity for carcinoembryonic antigen. Epithelial membrane antigen, Ber EP4 and S-100 were negative in all cases. Glial fibrillary acidic protein labelling occurred only in a single, poorly differentiated tumour. Occasional reactions for proliferating cell nuclear antigen and MIB-1 were seen in two cases. It was concluded that at least two morphological and possibly phenotypic subtypes (well-differentiated and anaplastic) of choroid plexus carcinoma of the dog could be identified.

A panel of immunohistochemical stains, including carcinoembryonic antigen, vimentin, and estrogen receptor, aids the distinction between primary endometrial and endocervical adenocarcinomas.

The histological distinction between a primary endometrial and a primary endocervical adenocarcinoma is often difficult, especially in small biopsy specimens. A preoperative distinction is important because primary surgical management differs between the two tumors. Cases of primary endometrioid endometrial (n=30) and primary endocervical (n=26) adenocarcinoma of endocervical type were stained immunohistochemically with the monoclonal antibodies against carcinoembryonic antigen (CEA), vimentin, estrogen receptor (ER), and 34 beta E12. In all cases the origin of the adenocarcinoma was confirmed by examination of the definitive pathology specimen. There was diffuse positive nuclear staining for ER in 28 of 30 (93%) endometrial adenocarcinomas. ER was negative in 16 of 26 endocervical adenocarcinomas, and there was focal weak nuclear staining in the other cases. Vimentin was positive in 29 of 30 (97%) endometrial adenocarcinomas but in only 2 of 26 (8%) endocervical adenocarcinomas. CEA was positive in 25 of 26 (96%) endocervical adenocarcinomas, mostly with diffuse membranous and cytoplasmic staining. Positivity with CEA was present in 21 of 30 (70%) endometrial adenocarcinomas but was largely confined to squamoid areas with only 12 tumors exhibiting focal membranous staining of the glandular component. 34 beta E12 was diffusely positive in all except one cervical adenocarcinoma. In endometrial carcinomas, positivity was strongest in squamoid areas but there was positive staining, either focally or diffusely, of the glandular component in 27 cases. In summary, primary endometrioid endometrial adenocarcinomas are characterized by diffuse, strong, positive staining for vimentin and ER and negative or very focal, positive staining of the glandular component for CEA. In contrast, primary endocervical adenocarcinomas are characterized by CEA positivity, which is usually but not always diffuse, negativity for vimentin, and negativity or focal weak positivity for ER. 34 beta E12 is of no value in the distinction between endometrial and endocervical adenocarcinomas. A panel of immunohistochemical stains, comprising CEA, vimentin, and ER, generally allows confident preoperative distinction between a primary endometrial and endocervical adenocarcinoma.

Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study.

We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction.

Use of a panel of markers in the differential diagnosis of adenocarcinoma and reactive mesothelial cells in fluid cytology.

To evaluate the use of a panel of markers to differentiate adenocarcinoma and the reactive/inflammatory process in fluid cytology, we stained 29 formalin-fixed, paraffin-embedded cell blocks of effusion fluid from patients with metastatic adenocarcinoma and 24 cell blocks from patients with benign effusion with mucicarmine and antibodies to carcinoembryonic antigen (CEA), B72.3, and calretinin. Positive staining with CEA, B72.3, and mucicarmine was seen in 22 (76%), 20 (69%), and 18 (62%) adenocarcinoma cases, respectively. All except 1 adenocarcinoma was negative for calretinin. No benign cases were positive for B72.3 and mucicarmine. In 1 benign case, scattered epithelial cells demonstrated weak positivity for CEA. The majority of combinations were 100% specific for adenocarcinoma. The highest sensitivity (86%) for adenocarcinomas was achieved with the staining combination of negative for calretinin and positive for any adenocarcinoma marker (CEA, B72.3, or mucicarmine). The use of a panel of markers that recognize adenocarcinoma and mesothelial cells is useful in the differential diagnosis between metastatic adenocarcinoma and the reactive/inflammatory process. The profile of positive staining with at least one of the adenocarcinoma markers and negative calretinin staining is highly specific and sensitive for identifying adenocarcinoma in fluid cytology.

Diagnostic value of preoperative RT-PCR-based screening method to detect carcinoembryonic antigen-expressing free cancer cells in the peritoneal cavity from patients with gastric cancer.

At present the most reliable method for the diagnosis of peritoneal micrometastasis of gastric cancer is peritoneal wash cytology, but the sensitivity of this method is low. The aim of the present study was to verify whether carcinoembryonic antigen (CEA) reverse transcriptase-polymerase chain reaction (RT-PCR) assay can enhance the sensitivity and specificity of conventional cytology, and to determine how this technique can improve the accuracy of peritoneal recurrence. The present study included 230 patients with gastric cancer. Preoperative peritoneal wash was done by a paracentesis, followed by conventional cytology, CEA measurement, and CEA RT-PCR of recovered fluid. The CEA RT-PCR assay yielded 40 (17%) positives, which included none of the 26 patients with benign disease. The incidence of positive cytology and CEA level in wash fluid was 19% and 15%, respectively. Logistic stepwise regression analysis revealed that lymph node status, depth of invasion, venous invasion, and the results of peritoneal cytological examination, and CEA RT-PCR assay were independently related to peritoneal recurrence. The CEA level in the wash fluid was not related to peritoneal recurrence. Peritoneal cytological examination was the most significant predictive factor for peritoneal recurrence with a sensitivity of 46%, specificity of 94% and accuracy of 73%, while the corresponding values of the CEA RT-PCR assay were 31%, 95%, and 73%. Combining cytological examination with CEA RT-PCR assay resulted in a sensitivity rate for peritoneal recurrence of 57%, an 11% improvement over that of cytology alone. The data indicate that the use of a combination of CEA RT-PCR and cytological assay is more likely to identify patients who will develop peritoneal recurrence. This may be useful for the classification of patients for the most suitable therapeutic trials.

Colorectal carcinoma liver metastases: clinical significance of preoperative measurement of serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels.

The clinical significance of preoperative levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) was evaluated in patients with colorectal carcinoma liver metastases. Preoperative serum CEA and CA 19-9 levels, the number and size of liver metastases, and survival data were analyzed retrospectively in 73 patients. Using the cutoff level of 5 ng/ml for CEA and 37 U/ml for CA 19-9, the positivity of these for detecting metastatic deposits were 81% and 56%, respectively. CEA level was correlated with the number (P = 0.0081) and size (P = 0.013) of liver metastases among patients with positive CEA level, while CA 19-9 level was correlated only with the number of liver metastases (P = 0.0072) among those with positive CA 19-9 level. In the overall series, preoperative CEA and CA 19-9 levels were correlated significantly with survival only at higher cutoff levels. In 46 patients undergoing curative hepatectomy, however, these levels were not correlated with survival, even at higher cutoff levels. In conclusion, the CEA level is closely associated with the extent of liver metastases, while the CA 19-9 level may reflect multiplicity of hepatic deposits. Preoperative measurement of serum CEA and CA 19-9 levels appears to be of some prognostic value.

Clinical Importance of Preoperative Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 Levels in Gastric Cancer

Although serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are commonly measured before surgery for gastric carcinoma, this clinical significance is not fully understood. We evaluated a total of 549 patients with gastric cancer who underwent gastrectomy. Levels of CEA and CA19-9 were measured preoperatively in all patients. We retrospectively analyzed correlations between CEA or CA19-9 and clinicopathologic features, and estimated the prognostic utility of the tumor markers by analyzing clinicopathologic characteristics of the carcinoma as a function of seropositivity or negativity of the antigens in combination or by raising the levels. The positivity rates of CEA (> or =5 ng/mL) and CA19-9 (> or =37 U/mL) were 19.5% and 18%, respectively. Serum CEA and CA19-9 positivity significantly correlated with depth of invasion, hepatic metastasis, and curativity. Forty-nine patients positive for both CEA and CA19-9 had significantly higher frequencies of lymph node metastasis, deeper invasion by the tumor, lower rates of curative resection (p < 0.01), and higher rates of hepatic metastasis (p < 0.05) than 377 patients with normal levels of CEA and CA19-9. Surgical outcomes of patients who were CEA- and CA19-9-positive were poorer than those of patients with normal CEA and CA19-9 levels (p < 0.01). Significant correlation was found between serum CEA and CA19-9 level (p < 0.001, r = 0.24). Doubling the threshold level of serum positivity to 10 ng/mL (CEA) and 74 U/mL (CA19-9) improved the prognostic value of these factors. However, multivariate analysis using Cox's hazards model revealed that only CEA positivity using the doubled threshold value (10 ng/mL) (p = 0.04, hazard ratio = 1.7), nodal involvement (p = 0.01, hazard ratio = 1.9), and depth of invasion (p = 0.02 hazard ratio = 1.5) significantly predicted prognosis. Carcinoembryonic antigen positivity using the doubled threshold level (10 ng/mL) was an important prognostic factor in patients with gastric cancer.

Lung Cancer in Women: Sex-Associated Differences in Survival of Patients Undergoing Resection for Lung Cancer

The aim of this study was to analyze various characteristics and survival in female patients treated surgically for lung cancer. Retrospective clinical study. From 1,242 consecutive cases of primary non-small cell lung cancer treated with pulmonary resection between June 1984 and December 1998, 337 female patients (27.1%) were chosen. Female patients had the following characteristics: a significantly younger age at onset (62.5 +/- 0.56 years vs 64.1 +/- 0.31 years for men), a higher frequency of adenocarcinoma (86.0% vs 48.3% for men), and smaller tumors (32.7 mm vs 38.3 mm in diameter for men). Peripheral tumors were significantly more common in women than men (71.8% vs 50.6%, respectively). Among 686 patients with a history of smoking, the women smoked significantly less often (12.8% vs 91.4% for men). Complete resection was achieved significantly less often in women (79.6% vs 85.2% for men); however, women having complete resection survived significantly longer than their male counterparts. Women with a postoperative negative carcinoembryonic antigen (CEA) had a significantly better prognosis than men; however, women with a postoperative positive CEA did not. Women > or = 60 years old survived significantly longer than their male counterparts, while women < 60 years old did not. Once the tumor was resected completely, women survived longer, partly due to the influence of life expectancy. However, the incidence of malignant effusion was higher and the rate of complete resection was lower in women.

Impact of cytokeratin-20 and carcinoembryonic antigen mRNA detection by RT-PCR in regional lymph nodes of patients with colorectal cancer.

The reported rates for tumour cell involvement in the locoregional lymph nodes of colorectal cancer vary greatly, depending on the method used and case selection. In order to further evaluate the clinical value of molecular biologic detection of tumour cells we investigated 102 histologically tumour-free (pN0) regional lymph nodes from 51 consecutive, completely resected (UICC R0) colorectal carcinoma specimens for the presence of tumour cell mRNA by RT-PCR specific for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20). Two lymph nodes located nearest to the primary tumour were investigated in each case. CK-20 mRNA was found in 31 of 51 patients (60.8%) and CEA mRNA in 30 of 51 patients (58.8%), respectively. Identical transcription patterns of CK-20 and CEA mRNA (both positive or both negative) were found in 38 of 51 patients (74.5%). There was a significantly higher proportion of cases with CEA positivity in the lymph nodes of tubulopapillary than of mucinous adenocarcinomas (P< 0.03). Detection of CK-20 and CEA mRNA correlated in nine of 12 cases (75.0%) with the risk of tumour recurrence (not significant) and showed a tendency towards shorter disease-free survival by univariate analysis (not significant). Our data indicate that CK-20 and CEA mRNA detection by RT-PCR may prove useful for the prediction of tumour recurrence of patients with pN0 colorectal carcinoma, although neither reach statistical significance in this series of patients. © 2000 Cancer Research Campaign

Moc-31, fibronectin and CEA in the differential diagnosis of malignant effusions: an immunocytochemical study.

In discriminating benign and malignant origins of cytologically suspicious effusion smears a panel of antibodies against carcinoembryonic antigen (CEA), Fibronectin (F) and MOC-31 was used with immuno-cytochemical techniques. One hundred and thirty seven effusions were studied of which 107 had a malignant and 30 a benign aetiology as determined by clinical and histological examination. Cytologically 24 were diagnosed as benign, 97 as malignant and 14 as suspicious. Staining for F was positive in all effusions of benign and 3 of malignant origin. MOC-31 was positive in 95 (88.8%) of effusions of malignant origin but none of benign origin. Positive CEA was observed in 43% of effusions of malignant origin and in 10 of benign origin. The combination of MOC-31 positivity measured the sensitivity and specificity of the cytological examination in cases where the cytological examination result was suspicious as did F positivity improve the sensitivity for a benign origin of the effusion. Positivity or negativity for CEA is less valuable than the other parameters.

Transitional cell carcinomas of the ovary and bladder are immunophenotypically different.

Transitional cell carcinoma (TCC) of the ovary is a subtype of ovarian cancer whose main characteristic is its histological resemblance to TCC of the bladder. Thrombomodulin (TM), a surface glycoprotein commonly expressed in normal and neoplastic urothelium, has been proven to be a good marker for TCC of the bladder. To better define the phenotype of TCC of the ovary, we investigated TM, cytokeratin 20 and carcinoembryonic antigen (CEA) expression in 15 TCCs of the ovary and compared their phenotype with that of 20 TCCs of the bladder, and 20 serous and 10 endometrioid carcinomas of the ovary. Immunostaining was performed on formalin-fixed, paraffin-embedded tissue sections using the avidin-biotin-peroxidase complex method. All 20 TCCs of the bladder stained for TM and cytokeratin 20, and 13 stained for CEA. None of the TCCs of the ovary reacted for TM or cytokeratin 20, and only two expressed CEA. All of the serous and endometrioid carcinomas were negative for TM and cytokeratin 20. CEA positivity was observed in two of the serous carcinomas, but in none of the endometrioid carcinomas. The immunophenotype of TCC of the ovary is similar to that of other surface carcinomas of the ovary, but differs from that of TCC of the bladder. Since immunohistochemical procedures are often used in the diagnosis and classification of both primary and metastatic tumours, it is important to be aware of these differences in immunophenotype.

Time-dependency of the prognostic effect of carcinoembryonic antigen and p53 protein in colorectal adenocarcinoma.

This study examined the prognostic information regarding the risk of postoperative tumor recurrence obtained by simultaneous determination of preoperative serum carcinoembryonic antigen (CEA) and immunohistochemical expression of p53 protein in tumor tissue from patients with colorectal carcinoma. A retrospective study of 174 patients (AJCC/UICC Stages I, II and III) was conducted. Serum CEA levels were determined by an enzyme-linked immunoadsorbent assay. Immunohistochemical expression of nuclear p53 protein was assessed in formalin fixed, paraffin embedded archival tumor tissue. The results of both factors were categorized by clinical and histopathologic variables. The relative prognostic significance of all factors with regard to disease free survival was assessed by Cox proportional hazards regression analysis. The stability of the predictive value of both markers was assessed: 1) by splitting the follow-up into three intervals and performing separate analyses for each period and 2) graphically by plotting the corresponding cumulative hazards ratio along the follow-up. Eighty-two (47%) tumors manifested overexpression of p53 protein and 60 tumors (34.4%) exhibited elevated serum CEA levels (cutoff value of 5 ng/mL). p53 positive immunostaining and elevated CEA levels were associated with low cumulative disease free survival at 60 months' of follow-up, and proved to have independent prognostic significance. Analysis performed in different time periods of follow-up showed that the prognostic effect of both markers was not stable over time. The predictive significance of CEA and p53 changed along the study periods. An elevated preoperative CEA level was an indicator of a high risk of recurrence only during the first 2 years after surgery (hazards ratio, 3.26; 95% confidence interval 95% CI, 1.65-6.42). The presence of p53 immunoreactivity in the primary tumor was an indicator of a high risk of recurrence only after the first year of follow-up (hazards ratio, 4.02; 95% CI, 1.68-9.6). The serum CEA level and expression of p53 protein provide complementary prognostic information. Time-dependency of the prognostic influence of both parameters should be taken into consideration when establishing postoperative predictive estimations.