Detection of blood-borne cells in colorectal cancer patients by nested reverse transcription-polymerase chain reaction for carcinoembryonic antigen messenger RNA: longitudinal analyses and demonstration of its potential importance as an adjunct to multiple serum markers.

The use of reverse transcription-PCR (RT-PCR) to analyze cells in the blood of cancer patients for the detection of mRNA expressed in tumor cells has implications for both the prognosis and the monitoring of cancer patients for the efficacy of established or experimental therapies. Carcinoembryonic antigen (CEA) is expressed on approximately 95% of colorectal, gastric, and pancreatic tumors, and on the majority of breast, non-small cell lung, and head and neck carcinomas. CEA shed in serum is useful as a marker in only approximately 50% of colorectal cancer patients and rarely is shed by some other carcinoma types. RT-PCR has been used previously to detect CEA mRNA in cells in the blood and lymph nodes of cancer patients. Under the assay conditions validated in the studies reported here, 34 of 51 (67%) patients with different stages of colorectal cancer had blood cells that were positive by RT-PCR for CEA mRNA, whereas none of 18 patients with colonic polyps were positive; 2 of 60 apparently healthy individuals (who were age and sex matched with the carcinoma patients and were part of a colon cancer screening program as controls) were marginally positive. The results of CEA PCR in the blood of the carcinoma patients and the other groups showed strong statistical correlation with the disease (P2 < 0.0001). Analyses were carried out to detect both serum CEA protein levels and CEA mRNA in blood cells of colorectal carcinoma patients by RT-PCR. For all stages of disease, 18 of 51 patients (35%) were positive for serum CEA, whereas 35 of 51 (69%) were positive by RT-PCR. More importantly, only 5 of 23 (20%) of stage B and C colorectal cancer patients were positive for serum CEA, whereas 16 of 23 (70%) were positive by RT-PCR. The use of two other serum markers (CA19.9 and CA72-4) for colorectal cancer in combination with serum CEA scored two additional patients as positive; both were positive by RT-PCR for CEA mRNA. Pilot long-term longitudinal studies conducted before and after surgery identified some patients with CEA mRNA in blood cells that were negative for all serum markers, who eventually developed clinical metastatic disease. The studies reported here are the first to correlate RT-PCR results for CEA mRNA in blood cells with one or more serum markers for patients with different stages of colorectal cancer, and are the first long-term longitudinal studies to use RT-PCR to detect CEA mRNA in blood cells of cancer patients. Larger cohorts will be required in future studies to define the impact, if any, of this technology on prognosis and/or disease monitoring.

A re-evaluation of carcinoembryonic antigen (CEA) as a serum marker for breast cancer: a prospective longitudinal study.

PURPOSE: Carcinoembryonic antigen (CEA) is still a widely used test for monitoring breast cancer, although recent reports discourage its routine use because of low sensitivity. This is a prospective study evaluating the efficacy of CEA and CA 15.3 in monitoring breast cancer. EXPERIMENTAL DESIGN: Serum CEA and CA 15.3 were measured in 2191 patients with either benign (n = 738) or malignant (n = 1453) breast diseases. Five hundred and forty-nine patients were monitored during postsurgical follow-up for either a minimum of 5 years or until time of recurrence. Fifty-three patients with metastases were also monitored during chemotherapy. RESULTS: Elevated CEA and CA 15.3 levels were found in 16.7% and 33.0% of patients, respectively. CEA sensitivity rose to 41.3% and CA 15.3 sensitivity rose to 80.8% in metastatic patients. The adjunct of CEA increased the CA 15.3 sensitivity by 6% in the overall population and by only 2.1% for patients with metastases. During postsurgical follow-up, CEA was elevated in 38.0% and CA 15.3 in 70.2% of patients with recurrence. The combination of CEA and CA 15.3 increased the overall sensitivity by only 1.4%. Longitudinal monitoring of 53 metastatic patients undergoing chemotherapy demonstrated that, when positive, both CEA and CA 15.3 paralleled response to treatment, although CA 15.3 was a significantly more powerful marker for determining response to treatment. The cost effectiveness ratio of CEA was clearly less favorable than that of CA 15.3. CONCLUSIONS: CEA monitoring should be considered an expensive and inefficient method of follow-up evaluation for breast cancer patients, and it provides no additional value when used in combination with CA 15.3.

Colorectal Kaposi's sarcoma in an HIV-negative male in association with ulcerative rectocolitis: a case report.

A rare case and the first reported in Italy of a classic form of colorectal Kaposi's sarcoma, associated with ulcerative rectocolitis, is presented. Following a total proctocolectomy, the patient was disease-free at four years. Some epidemiological risk factors such as sex, age, place of birth and both advanced malaria and immunodepressive therapies have also been evaluated. Thus far, only five similar cases have been reported in the literature. However, the epidemiological, clinical and prognostic features of this form of Kaposi's sarcoma must still be investigated.

Comparative analysis of CA 242 and CA 19-9 serum tumor markers in colorectal cancer patients. A longitudinal evaluation.

OBJECTIVE: Following the encouraging results obtained on CA 242 as an adjunctive marker for colorectal cancer this study was designed to compare the clinical behavior of CA 242 to that of its related marker CA 19-9. PATIENTS AND METHODS: Sera from 630 patients with benign (n = 201) or malignant (n = 429) colorectal diseases were evaluated. Moreover, 50 patients with colorectal cancer were longitudinally monitored during. post-surgical follow-up for either a minimum of 5 years or until time of recurrence. Serum CEA, CA 19-9 and CA 242 levels were determined before treatment and at each scheduled follow-up. RESULTS: The distribution of CA 242 levels in colorectal cancer patients demonstrated a similar positivity rate (32.9%) compared to that of CA 19-9 (29.8%), although both sensitivities were lower than that of CEA (43.8%). Moreover, elevated CA 242 serum levels were found in metastatic disease (58.2%). A longitudinal evaluation demonstrated that serum CEA, CA 19-9 and CA 242 levels were elevated in 63.9%, 63.9% and 66.7% of recurrences. Combined evaluation of CEA, CA 19-9 and CA 242 serum levels in the overall population demonstrated a complementarity of CEA with the latter two markers. Conversely, a highly significant correlation was observed, suggesting that the two assays might recognize the same macromolecular complex. CONCLUSION: CA 242 determination does not seem to offer a particular advantage over CA 19-9, while CEA remains the marker of choice in monitoring colorectal cancer patients.

Evaluation of the CA 242 tumor antigen as a potential serum marker for colorectal cancer.

OBJECTIVE: The present study was designed to define the performance of serum CA 242 as a marker in colorectal cancer patients. PATIENTS AND METHODS: Serum samples from 1,013 subjects (440 healthy volunteers, 384 patients with primary or recurrent colorectal carcinoma and 189 with benign colorectal diseases) were evaluated. RESULTS: The measurement of serum CA 242 levels in the population of healthy subjects demonstrated the presence of positive levels in approximately 5% of the cases. Interestingly, similar results (5.8%) were obtained in patients with benign colorectal disease, demonstrating the high specificity of CA 242. When serum samples from colorectal cancer patients were analyzed, a sensitivity of 34.9% was observed. Moreover, 18.6% Stage A and B patients had positive CA 242 levels, compared to 33.3% and 58.8% of Stage C and D patients, respectively, indicating a correlation with the stage of disease. A comparison between preoperative and immediate postoperative CA 242 levels showed a consistent relationship between the efficacy of surgery and the reduction in serum CA 242 levels; further, elevated CA 242 levels were present in the immediate postsurgical follow-up of patients undergoing palliative surgery. A longitudinal evaluation of serum CA 242 levels demonstrated that this marker was indicative of the status of disease. CONCLUSIONS: The results obtained suggest the possible utility of CA 242 in monitoring the disease status, providing a rationale for future studies focusing on the longitudinal monitoring of colorectal cancer patients.

Effects of isolated limb perfusion with tumor necrosis factor-alpha on circulating levels of proinflammatory cytokines.

Hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor-a (TNFalpha) and cytotoxic drugs is currently used for treatment of melanoma and sarcoma of the limbs. Tumor necrosis factor-alpha is involved in the systemic inflammatory response syndrome as a result of activation of inflammatory cells and production of bioactive substances. The goal of this study was to determine the circulating levels of proinflammatory cytokines and soluble adhesion molecules in 19 patients with limb melanoma or sarcoma undergoing ILP with (n = 9) or without TNFalpha (n = 10). The results obtained demonstrated that ILP with TNFalpha was responsible for a leakage of TNFalpha in the systemic circulation, followed by a rise in interleukin (IL)-6 and IL-8 levels within I h. Elevated soluble (s)P-selectin levels were found 1-3 h after ILP. Plasma sE-selectin peaked 6-9 h after ILP, and soluble vascular cell adhesion molecule (sVCAM) levels reached a maximum after 24 h. Significant correlations were observed among these variables, confirming the interdependence of all changes observed. On the other hand, ILP with cytotoxic drugs alone induced only a modest release of TNFalpha, which was not followed by an immediate rise in IL-6 and IL-8. Four of the 9 patients undergoing ILP with TNF had severe systemic toxicity. No association was found between systemic TNF levels and the clinical outcome, whereas elevated TNF perfusion levels as well as systemic IL-6 and IL-8 levels were constantly elevated in patients with severe toxicity. These results are suggestive of an important role of TNFalpha levels in the perfusion system (more than leakage of perfusate) in causing postoperative toxicity, although other ILP-related factors should not be excluded.

Serum tissue polypeptide specific antigen (TPS): a complementary tumor marker to CA 15-3 in the management of breast cancer.

The efficacy of CEA and CA15-3 tumor markers in monitoring breast cancer was evaluated in 1365 patients with either benign (n = 534) or malignant (n = 831) breast diseases. Thirty-nine breast cancer patients were monitored before and after neoadjuvant chemotherapy. Three hundred forty-nine patients were monitored during post-surgical follow-up for either a minimum of 5 years or until time of recurrence. Twenty-one patients with metastases were also monitored during chemotherapy. Elevated CA 15-3 and TPS levels were found in 28.6% and 30.0% of patients. CA 15-3 and TPS sensitivities rose to 71.9% and 66.3% in metastatic patients, respectively. The addition of TPS to CA 15-3 increased the sensitivity up to 44.4% in the overall population, and to 87.6% in patients with metastases. During post-surgical follow-up CA 15-3 was elevated in 65.7% and TPS in 61.3% of patients with recurrence. The combination of TPS and CA 15-3 increased the overall sensitivity by 12.7%. Longitudinal monitoring of metastatic patients undergoing chemotherapy demonstrated that, when positive, both CA 15-3 and TPS paralleled response to treatment. TPS monitoring may provide additional value when used in combination with CA15-3 during post-surgical follow-up of breast cancer patients.