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Correlation of CD44v6 expression with disease progression in locally excised T1 colorectal adenocarcinoma (CRC)
April 2000
AGAA513
2737
2739
INCREASED PLASMA GASTRIN LEVEL IN PATIENTS WITH COLORECTAL CANCER (CC) DECREASE AFTER TUMOR RE· SECTION.
DETECTION OF DISSEMINATED TUMOR CELLS IN BONE MARROW AND CIRCULATING BLOOD SAMPLE ISOLATED FROM ADENOCARCINOMA PATIENTS BY CEA·SPECIFIC RT· PCR.
Grzegorz Bombski, Daria Orszulak-Michalak, Beata Neneman, Ewa Malecka-Panas, Gastroenterology Ward, Regional Hosp, Piotrkow Tryb., Poland; Dept of Biopharmacy, Med Univ of Lodz, Lodz, Poland; Dept of Digest Tract Dis & Metab Dis, Med Univ, Lodz, Poland. Many studies have demonstrated that gastrin stimulates mucosal growth of much of the G.I. tract, and has also been implicated in promoting growth of colonic tumors. Inhibition of growth of human colorectal cancer (cq by gastrin receptor antagonists has been reported. However, the role of gastrin in colorectal carcinogenesis remains controversial. The aim of the study was to estimate fasting serum gastrin levels before and after surgery for CC and dependently on the clinical stage of the disease in order to investigate the possible prognostic role of this measurement. The study population comprised 50 patients with CC (22 men and 28 women, aged 46-85, mean 64 ± 8,7) and 10 well matched healthy controls. Among cancer patients 7 were of Dukes stage A, 12- of stage B, 10- of stage C and 21 of stage D. Fasting RIA gastrin levels (GASK-PR, CIS Bio) as well as Ca19-9 and CEA were measured before and 1-2 months after surgery for CC. H. pylori status was also assessed, since it causes significant hypergastrinemia. The mean gastrin level in control group was 40.3± 13.9 J.LUlml, which was significantly lower (p
2738 ANALYSIS OF SURVIVAL OF PATIENTS WITH METASTATIC (M:l) PANCREATIC ADENOCARCINOMA (PCA) FOUND ONLY ON ECHOENDOSCOPY (EUS). Khalid M. Moussa, Harry Snady, Howard Bruckner, Yale Univ - Norwalk Hosp, Norwalk, CT; Pancreatobiliary Treatment Group, New York, NY; St Luke's-Roosevelt Hosp Ctr, New York, NY. OBJECTIVE: Little information is known about EUS scanning criteria for metastatic PCa. As PCa extends out of the gland, survival usually decreases. This study was conducted to determine survival of patients with PCa who fulfilled EUS criteria for metastases compared to localized diseased, but with invasion of major regional vessels visible on computerized tomography (CT). METHODS: EUS was performed on 539 patients for evaluation of pancreatic disease. Of patients with presumed non metastatic PCa based on a CT which did not show distant disease, 29 were found to have M:1 disease based on the presence of at least one of the following: localized ascites (#7), hyperechoic splenic lesion (#1), hypo- or hyperechoic hepatic lesions (#20), granular hepatic pattern (#7), distant lymph nodes (#5), and peritoneal seeding (#3). All 29 patients had a clinical course consistent with progressi ve M: I disease and developed metastases that could be visualized on subsequent CT. During the same time interval, 17 patients referred with presumed regional PCa had invasion of major vessels that was visualized on CT. All patients were referred for chemotherapy. Survival was analyzed by the Kaplan-Meier method. RESULTS: Median survival of patients with regional PCa on initial CT, but metastases on EUS, was 8 months. Median survival of patients with regional, but unresectable, PCa based on CT, was 15mo. CONCLUSION: When EUS is positive for one of the above indicators for metastases, long term survival was poor, and worse than for patients with a CT showing invasive, nonmetastatic PCa. Further data is needed to determine whether the usefulness of these EUS criteria as prognostic indicators are limited by low sensitivity.
Akihiro Nakajo, Shoji Natsugoe, Keiichiro Uchikura, Futoshi Miyazono, Sumiya Ishigami, Hiroyuki Shinchi, Shuichi Hokita, Sonshin Takao, Takashi Aiko, Kagoshima Univ, Kagoshima, Japan. Purpose: Hematogenous metastasis is one of the important prognostic factors in patients with gastrointestinal carcinoma. The aim of this study was to clarify the incidence and clinical significance including outcome in the patients with disseminated tumor cells in bone marrow and blood. Materials and Methods: Samples of bone marrow and blood were obtained from fifty-one patients with adenocarcinoma (31 gastric cancer, 11 bile duct cancer, 9 pancreatic cancer). Blood samples collected from 20 patients with benign disease and 10 healthy volunteers were used as a control. Bone marrow samples were aspirated from anterior upper iliac crest, just before the laparotomy. Blood samples were obtained at two times during operation (after skin incision, and tumor resection) from peripheral artery, portal vein, and superior vena cava through the inserted catheters. In order to detect the disseminated tumor cells, these samples were analyzed by carcinoembryonic antigen (CEA) -specific nested reverse transcription polymerase chain reaction (RT-PCR). MKN-45 human gastric cancer cell lines were used to test the sensitivity of CEA specific RT-PCR. Results: CEA-mRNA was detected at the concentration as low as 10 tumor cells diluted among 106 normal lymphocytes. No signs of CEA-mRNA were detected either in the blood from patients with benign disease or healthy volunteers. In bile duct cancer patients, CEA-mRNA was detected in 3 of 11(27%) bone marrow and 7 of 11(64%) blood samples isolated during the operation. The detection rates of CEA-mRNA for bone marrow and blood in pancreatic cancer patients were 11% (1/9) and 78% (7/9), respectively. The number of positive findings in gastric cancer patients was 2 of 31(6.4%) in bone marrow and 15 of 31(50%) in blood samples. Almost patients with positive findings in bone marrow had advanced tumor. While, 7 patients with positive results in blood have already recurred in the mode of blood borne metastasis in spite of the short follow-up period. The significant relationship was found between the detection of circulating cancer cells and hematogenous tumor recurrence. Conclusions: Since some patient with CEA-mRNA positivity in bone marrow and blood had early tumor recurrence, the molecular detection of circulating cancer cells using CEA-specific RT-PCR may be useful for predicting hematogenous recurrence in patients with adenocarcinoma.
2740 CORRELATION OF CD44V6 EXPRESSION WITH DISEASE PRO· GRESSION IN LOCALLY EXCISED T 1 COLORECTAL ADENOCARCINOMA (CRC). Adrian H. Ormsby, Guy Cj Harris, Ian C. Lavery, THE CLEVELAND Clin Fdn, Cleveland, OH. Background: The ability to assess the risk of disease progression in patients with T [ colorectal adenocarcinoma treated primarily by local excision (that is, endoanal resection or colonoscopic polypectomy) would be useful in patient management. The cell adhesion molecule CD44 isoform 6 (CD44v6) has been associated with metastases in several human carcinomas. The aim of this study was to correlate the presence of CD44v6 expression and other pathologic parameters with disease progression, that is, tumor recurrence or death from colorectal disease, in locally excised T [ colorectal adenocarcinoma. Design: All patients with T[ colorectal adenocarcinoma treated primarily by local excision (n=38) at The Cleveland Clinic Foundation from 1980-1998 were identified. All cases (n=16) with adequate histologic material were immunostained for CD44v6 (clone: VFF7) and classified as positive (> 10% cytoplasmic staining of neoplastic cells) or negative, in blinded fashion. CD44v6 staining was correlated with the presence of pathologic features on matching Hematoxylin and Eosin stained histologic sections and included tumor grade (based on average) and the presence of angiolymphatic tumor invasion. Results: Mean patient age was 68.1 years (range:44-93 years) and 63% of the patients were male. Mean patient follow-up was 57 months (range: 17-117 months). 11 of 16 patients (69%) were CD44v6 positive. 3 of 16 patients (19%) had either recurrent colorectal adenocarcinoma (n=2) or died of colorectal carcinoma (n= 1) and all 3 cases were CD44v6 positive. 2 of 16 patients (12%) had high grade (poorly differentiated) colorectal adenocarcinoma, however, only 1 of these 2 cases had disease progression (died of colorectal carcinoma at 62 months). The sensitivitiy and specificity of CD44v6 expression for disease progression was 100% and 39%, respectively. Angiolymphatic invasion was not identified in any case. Conclusion: CD44v6 immunoreactivity is sensitive but not specific for disease progression in T[ locally resected colorectal adenocarcinoma. This may have application to surgical intervention of early colorectal adenocarcinoma in respect to local excision versus curative resection.
AGAA513
2737
2739
INCREASED PLASMA GASTRIN LEVEL IN PATIENTS WITH COLORECTAL CANCER (CC) DECREASE AFTER TUMOR RE· SECTION.
DETECTION OF DISSEMINATED TUMOR CELLS IN BONE MARROW AND CIRCULATING BLOOD SAMPLE ISOLATED FROM ADENOCARCINOMA PATIENTS BY CEA·SPECIFIC RT· PCR.
Grzegorz Bombski, Daria Orszulak-Michalak, Beata Neneman, Ewa Malecka-Panas, Gastroenterology Ward, Regional Hosp, Piotrkow Tryb., Poland; Dept of Biopharmacy, Med Univ of Lodz, Lodz, Poland; Dept of Digest Tract Dis & Metab Dis, Med Univ, Lodz, Poland. Many studies have demonstrated that gastrin stimulates mucosal growth of much of the G.I. tract, and has also been implicated in promoting growth of colonic tumors. Inhibition of growth of human colorectal cancer (cq by gastrin receptor antagonists has been reported. However, the role of gastrin in colorectal carcinogenesis remains controversial. The aim of the study was to estimate fasting serum gastrin levels before and after surgery for CC and dependently on the clinical stage of the disease in order to investigate the possible prognostic role of this measurement. The study population comprised 50 patients with CC (22 men and 28 women, aged 46-85, mean 64 ± 8,7) and 10 well matched healthy controls. Among cancer patients 7 were of Dukes stage A, 12- of stage B, 10- of stage C and 21 of stage D. Fasting RIA gastrin levels (GASK-PR, CIS Bio) as well as Ca19-9 and CEA were measured before and 1-2 months after surgery for CC. H. pylori status was also assessed, since it causes significant hypergastrinemia. The mean gastrin level in control group was 40.3± 13.9 J.LUlml, which was significantly lower (p
2738 ANALYSIS OF SURVIVAL OF PATIENTS WITH METASTATIC (M:l) PANCREATIC ADENOCARCINOMA (PCA) FOUND ONLY ON ECHOENDOSCOPY (EUS). Khalid M. Moussa, Harry Snady, Howard Bruckner, Yale Univ - Norwalk Hosp, Norwalk, CT; Pancreatobiliary Treatment Group, New York, NY; St Luke's-Roosevelt Hosp Ctr, New York, NY. OBJECTIVE: Little information is known about EUS scanning criteria for metastatic PCa. As PCa extends out of the gland, survival usually decreases. This study was conducted to determine survival of patients with PCa who fulfilled EUS criteria for metastases compared to localized diseased, but with invasion of major regional vessels visible on computerized tomography (CT). METHODS: EUS was performed on 539 patients for evaluation of pancreatic disease. Of patients with presumed non metastatic PCa based on a CT which did not show distant disease, 29 were found to have M:1 disease based on the presence of at least one of the following: localized ascites (#7), hyperechoic splenic lesion (#1), hypo- or hyperechoic hepatic lesions (#20), granular hepatic pattern (#7), distant lymph nodes (#5), and peritoneal seeding (#3). All 29 patients had a clinical course consistent with progressi ve M: I disease and developed metastases that could be visualized on subsequent CT. During the same time interval, 17 patients referred with presumed regional PCa had invasion of major vessels that was visualized on CT. All patients were referred for chemotherapy. Survival was analyzed by the Kaplan-Meier method. RESULTS: Median survival of patients with regional PCa on initial CT, but metastases on EUS, was 8 months. Median survival of patients with regional, but unresectable, PCa based on CT, was 15mo. CONCLUSION: When EUS is positive for one of the above indicators for metastases, long term survival was poor, and worse than for patients with a CT showing invasive, nonmetastatic PCa. Further data is needed to determine whether the usefulness of these EUS criteria as prognostic indicators are limited by low sensitivity.
Akihiro Nakajo, Shoji Natsugoe, Keiichiro Uchikura, Futoshi Miyazono, Sumiya Ishigami, Hiroyuki Shinchi, Shuichi Hokita, Sonshin Takao, Takashi Aiko, Kagoshima Univ, Kagoshima, Japan. Purpose: Hematogenous metastasis is one of the important prognostic factors in patients with gastrointestinal carcinoma. The aim of this study was to clarify the incidence and clinical significance including outcome in the patients with disseminated tumor cells in bone marrow and blood. Materials and Methods: Samples of bone marrow and blood were obtained from fifty-one patients with adenocarcinoma (31 gastric cancer, 11 bile duct cancer, 9 pancreatic cancer). Blood samples collected from 20 patients with benign disease and 10 healthy volunteers were used as a control. Bone marrow samples were aspirated from anterior upper iliac crest, just before the laparotomy. Blood samples were obtained at two times during operation (after skin incision, and tumor resection) from peripheral artery, portal vein, and superior vena cava through the inserted catheters. In order to detect the disseminated tumor cells, these samples were analyzed by carcinoembryonic antigen (CEA) -specific nested reverse transcription polymerase chain reaction (RT-PCR). MKN-45 human gastric cancer cell lines were used to test the sensitivity of CEA specific RT-PCR. Results: CEA-mRNA was detected at the concentration as low as 10 tumor cells diluted among 106 normal lymphocytes. No signs of CEA-mRNA were detected either in the blood from patients with benign disease or healthy volunteers. In bile duct cancer patients, CEA-mRNA was detected in 3 of 11(27%) bone marrow and 7 of 11(64%) blood samples isolated during the operation. The detection rates of CEA-mRNA for bone marrow and blood in pancreatic cancer patients were 11% (1/9) and 78% (7/9), respectively. The number of positive findings in gastric cancer patients was 2 of 31(6.4%) in bone marrow and 15 of 31(50%) in blood samples. Almost patients with positive findings in bone marrow had advanced tumor. While, 7 patients with positive results in blood have already recurred in the mode of blood borne metastasis in spite of the short follow-up period. The significant relationship was found between the detection of circulating cancer cells and hematogenous tumor recurrence. Conclusions: Since some patient with CEA-mRNA positivity in bone marrow and blood had early tumor recurrence, the molecular detection of circulating cancer cells using CEA-specific RT-PCR may be useful for predicting hematogenous recurrence in patients with adenocarcinoma.
2740 CORRELATION OF CD44V6 EXPRESSION WITH DISEASE PRO· GRESSION IN LOCALLY EXCISED T 1 COLORECTAL ADENOCARCINOMA (CRC). Adrian H. Ormsby, Guy Cj Harris, Ian C. Lavery, THE CLEVELAND Clin Fdn, Cleveland, OH. Background: The ability to assess the risk of disease progression in patients with T [ colorectal adenocarcinoma treated primarily by local excision (that is, endoanal resection or colonoscopic polypectomy) would be useful in patient management. The cell adhesion molecule CD44 isoform 6 (CD44v6) has been associated with metastases in several human carcinomas. The aim of this study was to correlate the presence of CD44v6 expression and other pathologic parameters with disease progression, that is, tumor recurrence or death from colorectal disease, in locally excised T [ colorectal adenocarcinoma. Design: All patients with T[ colorectal adenocarcinoma treated primarily by local excision (n=38) at The Cleveland Clinic Foundation from 1980-1998 were identified. All cases (n=16) with adequate histologic material were immunostained for CD44v6 (clone: VFF7) and classified as positive (> 10% cytoplasmic staining of neoplastic cells) or negative, in blinded fashion. CD44v6 staining was correlated with the presence of pathologic features on matching Hematoxylin and Eosin stained histologic sections and included tumor grade (based on average) and the presence of angiolymphatic tumor invasion. Results: Mean patient age was 68.1 years (range:44-93 years) and 63% of the patients were male. Mean patient follow-up was 57 months (range: 17-117 months). 11 of 16 patients (69%) were CD44v6 positive. 3 of 16 patients (19%) had either recurrent colorectal adenocarcinoma (n=2) or died of colorectal carcinoma (n= 1) and all 3 cases were CD44v6 positive. 2 of 16 patients (12%) had high grade (poorly differentiated) colorectal adenocarcinoma, however, only 1 of these 2 cases had disease progression (died of colorectal carcinoma at 62 months). The sensitivitiy and specificity of CD44v6 expression for disease progression was 100% and 39%, respectively. Angiolymphatic invasion was not identified in any case. Conclusion: CD44v6 immunoreactivity is sensitive but not specific for disease progression in T[ locally resected colorectal adenocarcinoma. This may have application to surgical intervention of early colorectal adenocarcinoma in respect to local excision versus curative resection.