gastrins and Colonic-Polyps

Topics: Barrett Esophagus; Carcinoma, Neuroendocrine; Colonic Polyps; Diagnosis, Differential; Diarrhea; Gastrinoma; Gastrins; Humans; Male; Middle Aged; Pancreatic Neoplasms; Recurrence; Vomiting; Weight Loss; Zollinger-Ellison Syndrome

In contrast to sessile serrated adenomas and traditional serrated adenomas which are associated with a significant cancer risk, the role of hyperplastic polyps (HP) in colorectal carcinogenesis as well as the molecular mechanisms underlying their development remain controversial and still need to be clarified. Several reports suggest that a subset of HP may represent precursor lesions of some colorectal cancers. However, biomarkers are needed to identify the subset of HP that may have a malignant potential. The hormone precursor, progastrin (PG) has been involved in colon carcinogenesis and is known to activate pro-oncogenic pathways such as the ERK or the STAT3 pathway. We therefore analyzed PG expression and the activation of these signaling factors in HP.. We retrospectively analyzed PG expression as well as the phosphorylation of ERK and STAT3 by immunohistochemistry in HP from 48 patients.. Mean percentages of epithelial cells positive for PG or phospho-ERK were respectively, 31% and 33% in HP and were significantly higher in these lesions compared to normal colon (3%, p=0.0021 and 7%, p=0.0008, respectively). We found a significant correlation between PG and phospho-ERK expression in HP with ERK activation significantly stronger in lesions with high progastrin expression (p=0.015). In contrast, STAT3 was not significantly activated in HP compared to normal colon and we did not observe a significant correlation with PG expression.. HP overexpressing PG that have the highest activation of the ERK pathway might reflect less latent lesions that might have a malignant potential.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Colonic Polyps; Extracellular Signal-Regulated MAP Kinases; Female; Gastrins; Humans; Hyperplasia; Intestinal Mucosa; Male; Middle Aged; Oncogene Proteins; Protein Precursors; Retrospective Studies; Risk Factors; Signal Transduction; STAT3 Transcription Factor

The most frequently occurring lesions in the colon are the hyperplastic polyps. Hyperplastic polyps have long been considered as lesions with no malignant potential and colonoscopy for these patients is not recommended. However, recent works suggest that hyperplastic polyps may represent precursor lesions of some sporadic colorectal cancers. Until now, no biomarker allows to identify the subset of hyperplastic polyps that may have a malignant potential. Because the hormone precursor progastrin has been involved in colon carcinogenesis, we investigated whether its expression in hyperplastic polyps predicts the occurrence of colonic neoplasm after resection of hyperplastic polyps. We retrospectively analyzed progastrin expression in hyperplastic polyps from 74 patients without history of colorectal pathology. In our study, 41% of patients presenting an initial hyperplastic polyp subsequently developed adenomatous polyps, recognized as precursor lesions for colorectal adenocarcinomas. Progastrin was overexpressed in the hyperplastic polyps in 40% of the patients. We showed a significant association between progastrin overexpression and shortened neoplasm-free survival (P = 0.001). Patients with high overexpression of progastrin had a 5-year neoplasm-free survival rate of 38% as compared with 100% for the patients with low progastrin expression. In addition, we established a predictive test on the basis of progastrin staining and patients' age that predicts occurrence of neoplasm after developing a first hyperplastic polyp with a sensitivity of 100% [95% confidence interval (CI), 79%-100%] and a specificity of 74% (51%-90%). We show that progastrin expression evaluation in hyperplastic polyps is an efficient prognostic tool to determine patients with higher risk of metachronous neoplasms who could benefit from an adapted follow-up.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cohort Studies; Colonic Neoplasms; Colonic Polyps; Disease-Free Survival; Female; Gastrins; Humans; Immunohistochemistry; Male; Middle Aged; Protein Precursors; Reproducibility of Results; ROC Curve

The relationship between plasma gastrin levels and colorectal cancer is controversial. When confounding factors which increase plasma gastrin levels are taken into account, it has been shown that gastrin levels are not elevated in patients with colorectal cancer. However, these studies only measured amidated gastrin. Total gastrin (which includes unprocessed, partially processed, and mature forms of gastrin) has been shown to be elevated in patients with colorectal cancer.. The aim of this study was to determine whether fasting plasma levels of progastrin, amidated gastrin, or glycine extended gastrin are elevated in patients with colorectal cancer or colorectal polyps compared with controls.. Progastrin, amidated gastrin, and glycine extended gastrin were estimated by radioimmunoassay using the following antibodies: L289, 109-21, and L2. Blood samples were analysed for Helicobacter pylori by an enzyme linked immunosorbent assay.. Median progastrin levels were significantly higher in the cancer group (27.5 pmol/l) than in the polyp (< or =15 pmol/l) or control (< or =15 pmol/l) group (p=0.0001 There was no difference in median levels of amidated gastrin between groups. Median levels of amidated gastrin were significantly higher in H pylori positive patients (19 pmol/l) than in H pylori negative patients (8 pmol/l) (p=0.0022). Median plasma progastrin levels were significantly higher for moderately dysplastic polyps (38 pmol/l) compared with mildly dysplastic (15 pmol/l) and severely dysplastic (15 pmol/l) polyps (p=0.05).. Plasma levels of progastrin, but not amidated gastrin or glycine extended gastrin, are significantly elevated in patients with colorectal cancer compared with those with colorectal polyps or controls, irrespective of their H pylori status. We conclude that measuring plasma progastrin levels in patients with colorectal cancer is warranted.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Biomarkers, Tumor; Carcinoma; Case-Control Studies; Colonic Polyps; Colorectal Neoplasms; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Protein Precursors

Gastrin and the cholecystokinin type B/gastrin receptor (CCKBR) have been shown to be expressed in colorectal adenocarcinoma. Both exogenous and autocrine gastrin have been demonstrated to stimulate growth of colorectal cancer but it is not known if gastrin affects the growth of colonic polyps. The purpose of this study was to determine if gastrin and CCKBR are expressed in human colonic polyps and to determine at which stage of progression this occurs.. A range of human colonic polyps was assessed for gastrin and CCKBR gene and protein expression.. Normal colonic mucosa did not express gastrin or CCKBR. Gastrin and CCKBR reverse transcription-polymerase chain reaction products were detected and verified by specific hybridisation with an oligo probe on Southern blots. Gastrin and CCKBR were expressed in 78% and 81% of polyps, respectively. Both genes were coexpressed in 97% of cases. Immunohistochemistry identified progastrin in 91%, glycine extended gastrin 17 in 80%, and amidated gastrin 17 in only 47% of polyps. CCKBR was present in 96% of polyps. Expression of gastrin and CCKBR was seen in all histological types and sizes of polyps.. This study is the first to show widespread expression of both gastrin and its receptor in colorectal polyps. Their activation occurs early in the adenoma-carcinoma sequence. Gastrin may promote progression through the adenoma-carcinoma sequence.

Topics: Adenoma; Aged; Carcinoma; Colonic Neoplasms; Colonic Polyps; Disease Progression; Female; Gastrins; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Proteins; Precancerous Conditions; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Reverse Transcriptase Polymerase Chain Reaction

Whereas considerable experimental evidence suggests chronic hypergastrinemia can increase the occurrence of colonic neoplasia, the risks in man remain unclear. Zollinger-Ellison syndrome (ZES) is associated with marked plasma elevation of all forms of gastrin and, because of its prolonged course, has been shown to be an excellent model disease to study the effects of chronic hypergastrinemia in man. To determine whether profound chronic hypergastrinemia affects the occurrence of colonic dysplasia and neoplasia, 97 consecutive patients with ZES were studied. All patients underwent colonoscopic examination to the cecum, and the location, size, and type of polyps/tumors were determined. The patients had a mean fasting gastrin level 31 times above normal and a mean disease duration of 10 years; 17/97 (18%) had adenomatous polyps, 67/97 (69%) no adenomatous polyps, and 2/97 (2%) had colonoscopy and/or autopsy studies fo asymptomatic controls. Stratification by age or gender, presence of MEN-I, tumor extent, and duration of degree of hypergastrinemia did not increase prevalence. This study shows that despite prolonged, profound hypergastrinemia, no increased rate of colonic neoplasia (polyps or cancer) was noted. These data suggest that the development of hypergastrinemia secondary to continuous use of H+,K+-ATPase inhibitors for as long as 10 years is unlikely to cause an increased risk of developing colonic neoplasia in man.

Topics: Adenocarcinoma; Adenomatous Polyps; Age Distribution; Chronic Disease; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Fasting; Female; Gastrins; Humans; Incidence; Male; Middle Aged; Risk Factors; Sex Distribution; Zollinger-Ellison Syndrome

Confirmation of an association between elevated serum gastrin concentrations and presence of colorectal tumors would have important implications with regard to screening procedures and therapeutic strategies.. We compared fasting serum gastrin concentrations of patients with colorectal cancer (n = 91; mean age, 66 (range, 35-87) years), colorectal polyps (n = 89; mean age, 61 (range, 38-86) years), or a normal colonoscopy (n = 101; mean age, 62 (range, 34-82) years) in the period between 1983 and 1992.. Median serum gastrin concentrations were, respectively, 20, 20, and 21 pmol/liter (not significant). We were unable to find a relation with histology of the polyp, presence or severity of dysplasia, and extent of cancer.. This large study fails to show any difference in serum gastrin concentrations among the three studied groups.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Female; Gastrins; Humans; Male; Middle Aged; Neoplasm Staging; Retrospective Studies

During the last years interest has focused on the trophic effect of gastrin in colorectal carcinomas. Some reports indicated an increased serum level of gastrin in patients with colorectal adenomas or carcinomas. In a prospective study in 261 patients submitted to colonoscopy fasting serum gastrin concentrations were determined. 91 patients served as control, 89 patients had one or more adenomas, 55 patients suffered from a colorectal carcinoma, 17 had a benign, postoperative stenosis of the colon, and 9 had a chronic inflammatory bowel disease. All patients fulfilled the following criteria: No regular drug intake, no previous gastric or small bowel operation, no known ulcer disease, no abnormalities in serum calcium, creatinine, triglycerides, cholesterol and blood urea. Mean gastrin level was 86.63 +/- 23.8 pg/ml in the control, 84.57 +/- 25.1 pg/ml in the adenoma group and 84.6 +/- 24.4 pg/ml in the carcinoma group. No difference of serum gastrin levels were observed regarding sex, age, tumor stage and localisation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Colonic Diseases; Colonic Polyps; Colorectal Neoplasms; Female; Gastrins; Humans; Inflammatory Bowel Diseases; Intestinal Obstruction; Male; Middle Aged; Postoperative Complications

Topics: Adenocarcinoma; Colonic Neoplasms; Colonic Polyps; Gastrins; Humans

Gastrin stimulates the growth of some human colon adenocarcinomas grown in vitro or as xenografts in nude mice. To evaluate the possibility of elevated plasma gastrin levels in patients with adenomatous polyps or colorectal cancer, we carried out a radioimmunoassay in subjects fasting overnight and undergoing colonoscopy. The study included 190 patients who were divided into three groups: controls (n = 65), those with benign adenomas (n = 63), and those with adenocarcinomas (n = 62). The mean values of plasma gastrin in the cancer group (112.71 +/- 16.65 pg/ml) were significantly higher than those of the control group (40.41 +/- 1.88 pg/ml) as well as those of the polyp group. Mean plasma gastrin values in the polyp group (54.27 +/- 5.29 pg/ml) were also significantly higher than those of the control group. In the cancer group, 32 of 62 patients (51.6%) had gastrin levels greater than the control mean +2 SD, as opposed to only 10 of 63 (15.9%) in the polyp group. The number, size, histologic type, and presence of dysplasia in the polyp group and the location or Dukes' stage in the cancer group had no significant influence on gastrin levels in this study. Preliminary results in cancer patients with elevated preoperative gastrin levels show a postoperative reduction in six of seven patients. The exact cause and role of hypergastrinemia in tumor growth in such patients remains to be determined. Measurements taken both before and after colectomy coupled with a systematic search for specific gastrin receptors would be useful.

Topics: Adenocarcinoma; Aged; Colonic Neoplasms; Colonic Polyps; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Rectal Neoplasms

The trophic effect of gastrin in the intestine has been shown. Fasting gastrin levels of patients with adenomatous polyps or adenocarcinoma and in control subjects were determined (n = 141). The mean value of fasting gastrin of control subjects (n = 75) was 47.1 pg/ml +/- 17.8, of patients with adenomatous polyps (n = 49) 49.8 pg/ml +/- 20.7, of patients with carcinoma (n = 17) 50.1 pg/ml +/- 23.3. Neither in the group of patients with adenomatous polyps nor in the group of patients with carcinoma, fasting gastrin levels were elevated compared to control subjects. Our study indicates that there is no significant difference in fasting gastrin between either group (control subjects, colon polyps and carcinoma).

Topics: Aged; Carcinoma; Colonic Polyps; Colorectal Neoplasms; Fasting; Female; Gastrins; Humans; Male; Middle Aged

Topics: Colonic Polyps; Colorectal Neoplasms; Gastrins; Humans

Gastrin has been shown to stimulate the growth of carcinogenic-induced colon cancer in animals, and some human colon cancers grown in vitro or as xenografts in nude mice. We determined fasting plasma gastrin levels in control subjects and patients with adenomatous polyps or adenocarcinoma of the colon to determine whether abnormal levels occurred in either patient group. Blood samples were obtained from 73 patients undergoing colonoscopy, primarily for evaluation of Hemoccult-positive stools. Fasting plasma gastrin was significantly greater in patients with adenomatous polyps (24.2 +/- 5.7 pM, N = 25) or colon cancer (84.5 +/- 28.5 pM, N = 20) than in controls (9.9 +/- 0.9 pM, N = 28). Elevations were due to gastrin values greater than control mean + 2 SD in nine patients with polyps (19.5-150.2 pM) and eight with cancer (20.7-403.2 pM). None of the patients had identifiable causes (drugs, prior surgery) for elevated gastrin levels. Our results indicate that elevated plasma gastrin occurs in subgroups of patients with adenomatous polyps or adenocarcinoma of the colon. The cause and potential role of elevated gastrin for polyp and tumor growth in these patients is not known.

Topics: Adenocarcinoma; Aged; Colonic Neoplasms; Colonic Polyps; Fasting; Female; Gastrins; Humans; Male; Middle Aged