No loss of sst receptors gene expression in advanced stages of colorectal cancer. (33/13490)

As demonstrated by several studies, the pan-inhibitory peptide somatostatin (SS) is implicated in a large variety of physiological processes in the gastrointestinal tractus. SS inhibits hormonal and gastric acid secretions, and decreases gastric and intestinal motility, mesenteric blood flow and intestinal absorption. In vitro and in vivo studies showed also that the antiproliferative potency of SS analogs may be a target to improve the prognosis of colorectal cancer. Here we report the expression profile of the five SS receptor subtypes (hsst1-5) mRNAs in a large set of tumoral and normal colon. Using reverse transcription-PCR, we showed that hsst5, hsst1 and hsst2 mRNA subtypes were the most frequently expressed hsst mRNA subtypes in normal and pathological colon. Interestingly, we found that the frequency of hsst5 mRNA expression in the left colon was significantly higher in tumors than in normal samples: 81. 2% (13/16) and 36.4% (4/11) respectively (0.025>P>0.01, chi2 test with Yates' correction). We did not find any influence of Dukes' stage on hsst mRNAs expression. Of interest, no loss of hsst2 and hsst5 mRNA expression in advanced stages was noted. Some differences in the frequency of expression of hsst mRNAs according to the origin of the tissue (left or right colon) were evident. The expression of hsst5 and hsst2 mRNA in advanced colorectal carcinoma associated with the development of new SS analogs boost the relevance of colorectal cancer treatment by somatostatin analogs.  (+info)

FasL is more frequently expressed in liver metastases of colorectal cancer than in matched primary carcinomas. (34/13490)

Colorectal carcinoma cells have recently been shown to express Fas ligand (FasL). This ligand could allow the tumour cells to evade activated tumour-infiltrating lymphocytes (TILs) by inducing their apoptosis and would thus promote tumour survival and possibly metastasis formation. To test this hypothesis in vivo we analysed the expression of FasL mRNA and protein in paired tissue samples of normal colonic mucosa (N), primary colorectal carcinomas (T) and their metastases (M) from a total of 21 patients by four different methods. Additionally, the presence and activation status of infiltrating lymphocytes, which might contribute to the total amount of FasL in the tissue, was determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in the same samples. The frequency of FasL detection was 30-40% in T and was 60-100% in M, depending on the sensitivity of the method. Simultaneously, the amount of CD25 mRNA, used as a measure of the number of activated TILs, was in 90% of patients lower in M than in T. The increased frequency of FasL detection in liver metastases was therefore not due to the presence of activated TILs. We conclude that metastasizing subpopulations of colorectal tumour cells express FasL more frequently than the primary carcinomas and may be able to eliminate activated TILs in vivo via Fas/FasL-induced apoptosis or other hitherto unknown mechanisms.  (+info)

Immuno-histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumor and non-tumor tissue sections. (35/13490)

Human telomerase is expressed in germ tissues and in the majority of primary tumors. Cell renewal tissues and some pre-cancerous tissues also have weak telomerase activity. Yet, neither the exact location and frequency of telomerase-positive cells nor the changes in telomerase expression during differentiation or carcinogenesis of individual cells are known. This paper reports on the expression of hTERT (telomerase reverse transcriptase) protein in tumor and non-tumor colorectal tissues by Western blotting and tissue sections by immunohistochemistry using antibodies raised against partial peptides of hTERT. Though telomerase activity and hTERT expression at both mRNA and protein levels were generally higher in tumor part than in non-tumor part, these two were not always correlated: expression of hTERT did not always give rise to high telomerase activity. Colonic carcinoma cell nuclei were stained with anti-hTERT antibodies but not with antigen-preabsorbed antibodies. In normal mucosa, hTERT protein was expressed, though weaker than in carcinoma, in all colonic crypt epithelial cells except those at the tip; the expressing-cell distribution was much wider than that of Ki-67 positive cells which were located at the bottom of the crypt. Isolated crypt contained a significant level of hTERT protein revealed by Western blotting, while having very weak telomerase activity. Telomerase activity was detected in epithelial cells only at the bottom half of the crypt. Specific hTERT-staining was positive in tissue lymphocytes but negative in almost all other stromal cells. It is of interest to see whether a significant level of hTERT expression with low telomerase activity is characteristic of physiologically regenerating tissues containing stem cells. In situ detection of the hTERT protein will permit further analysis of cancer diagnosis and stem cell differentiation.  (+info)

Incompleteness and retrieval of case notes in a case note audit of colorectal cancer. (36/13490)

Hospital case notes are a crucial source of data but are subject to two major biases: incompleteness of data and non-retrieval. To assess these biases in relation to colorectal cancer a study was performed of all cases of colorectal cancer listed in the Thames cancer registry in patients resident in one of four districts in South Thames regions with a diagnosis in 1988. Five medical record sites were involved. Retrieval rate for all case notes for districts combined was 80%. In two districts the rates were too high for further investigation; in the other two respectively patient survival and whether treatment was given were positively associated with retrieval. Among the four districts incompleteness of notes ranged from 38% to 62% for staging, 8% to 40% for treatment, and 70% to 25% for diagnostic tests. Information about treatment was missing in 3% to 20%; survival data were omitted in less than 5%. In all districts completeness of case notes was inadequate and in some non-retrieval compounded the problem. Missing data reduce the quality of cancer registry data and potentially undermine interpretation of epidemiological studies and evaluation of care. Further research is warranted into the standards and resourcing of medical records departments and their effects on retrieval and data quality. Structured proformas could be applied across specialties to identify missing items in case notes, to identify areas where standards are required, or to audit notes where standards have already been agreed. A staging protocol to set standards for colorectal cancer has been adopted in one district, and a prospective audit is being established.  (+info)

Reliability of data of the Thames cancer registry on 673 cases of colorectal cancer: effect of the registration process. (37/13490)

OBJECTIVE: To measure the reliability of data collected by the Thames cancer registry and to identify factors in the registration process affecting reliability. DESIGN: A retrospective study of data from the registry, including death certificate only registrations, and hospital case notes on cases of colorectal cancer diagnosed in 1983 or 1988. SETTING: Four districts in South Thames region. SUBJECTS: 673 cases of colorectal cancer in resident patients. MAIN MEASURES: Dates of birth, diagnosis of cancer, and death; sex; tumour site; whether treatment was given; type of treatment; and district of residence. RESULTS: Among the 416 (62%) case notes retrieved, including 66 death certificate only registrations, full or high agreement between registry data and hospital notes was recorded for sex, district of residence, and dates of birth and death. Only 12% of cases had the same date of diagnosis, which may be due to failure of registry policy. Lower agreement rates occurred for tumour site (87%), whether treatment occurred (84%), and treatments administered (80%, 1983; 72%, 1988). 20% of surgical treatments and 37% of adjuvant therapy, radiotherapy, and chemotherapy were not recorded by the registry. Disagreements were common among death certificate only registrations. Such registrations accounted for 16(32%) disagreements over tumour site, 33(41%) major disagreements over date of diagnosis (difference > 30 days), and 47(44%) disagreements over treatment. In 65 cases the registry failed to capture all treatments carried out within the six month follow up period, 38(58%) of which were for death certificate only registrations. In 36% of death certificate only registrations the patients survived more than one year from diagnosis, indicating a failure of registry policy over retrospective follow up. CONCLUSIONS: Registry data on district of residence; sex; dates of birth, diagnosis, and death are highly reliable, but treatment and tumour site data are less so. Lack of follow up in death certificate only registrations and failure to monitor treatments during follow up period seemed to be associated with disagreements.  (+info)

Increasing compliance with colorectal cancer screening: the development of effective health education. (38/13490)

The ability of a health education leaflet to raise awareness of the frequency of colorectal cancer and its asymptomatic nature and to increase intention to participate in screening with faecal occult blood testing (FOBT) was investigated. One hundred subjects were interviewed before and after reading the leaflet. The number of men stating bowel cancer was 'very common' increased significantly from 20 to 60% (chi 2 = 16.7, P < 0.0001) and those understanding its asymptomatic nature form 64 to 92% (chi 2 = 11.4, P < 0.001). The leaflet significantly increased the percentage of women reporting bowel cancer as 'very common' from 30 to 70% (chi 2 = 16.0, P < 0.0001) and as being asymptomatic from 58 to 94% (chi 2 = 17.8, P < 0.0001). After reading the leaflet, 55% of men who initially declined screening reversed their decision (chi 2 16.5, P < 0.0001) and 50% of female non-adherers reversed their decision (chi 2 = 17.3, P < 0.0001). Reasons most frequently given for declining colorectal cancer screening were feeling well (77% of subjects declining), concern about further tests (38%), unpleasantness of FOBT (13%) and illness (6%). This leaflet successfully educates people about colorectal cancer and increased intention to participate in screening programmes.  (+info)

Flat adenomas exist in asymptomatic people: important implications for colorectal cancer screening programmes. (39/13490)

BACKGROUND: Flat adenomas are non-exophytic with a flat top or central depression and histologically the depth of dysplastic tissue is never more than twice the mucosal thickness. Flat adenomas frequently contain severely dysplastic tissue, and may progress rapidly through the adenoma-carcinoma sequence. Flat lesions have never been described in a British asymptomatic population. AIMS: To determine whether flat adenomas exist in an asymptomatic population participating in a large randomised controlled trial of flexible sigmoidoscopy screening. PATIENTS: A total of 3000 subjects (aged 55-64 years) underwent screening by flexible sigmoidoscopy. METHODS: All polyps were removed and sent for histology. The number of polyps with endoscopic and histological features of flat adenomas was recorded. RESULTS: Three subjects had a total of four flat lesions--that is, one per 1000 people screened. Three contained severely dysplastic tissue, one a focus of adenocarcinoma. Three of the four lesions were less than 5 mm in size and the fourth was 15 mm in diameter. CONCLUSIONS: Flat lesions with severe dysplasia exist in the asymptomatic population. This has major implications for gastroenterologists who should be trained to identify them. Their existence is of importance to molecular biologists and epidemiologists investigating the aetiology of colorectal cancer.  (+info)

Ki-67: a useful marker for the evaluation of dysplasia in ulcerative colitis. (40/13490)

AIMS: Evaluation of dysplasia in long standing ulcerative colitis is a difficult and often subjective task. Therefore, the aim of this study was to search for a more objective parameter to help distinguish regenerative changes from epithelial dysplasia. METHODS: A total of 97 sections from colectomy specimens from 12 patients with ulcerative colitis of more than 10 years duration were stained immunohistochemically with MIB 1 to detect differences in the frequency and pattern of nuclei positive for the proliferation marker Ki-67. All patients had epithelial dysplasia in one or more areas (high grade dysplasia, n = 16; low grade dysplasia, n = 15; indefinite for dysplasia, n = 16), and three patients had additional adenocarcinoma (one Dukes's C multifocal, mucinous carcinoma; one Dukes's C adenocarcinoma in the sigmoid; and one Dukes's A adenocarcinoma in the caecum). Two patients had adenomas--one had an 8 cm villous adenoma with intramucosal carcinoma, and the other had a 4 cm tubulovillous adenoma with high grade dysplasia. RESULTS: There were highly significant differences between the percentages of Ki-67 immunopositive cells in low grade and high grade dysplasia and carcinoma compared with regenerative epithelium. In high grade dysplasia and carcinoma, the distribution of Ki-67 positive cells was diffuse throughout the full length of the crypt, whereas low grade dysplasia and epithelium indefinite for dysplasia, as well as regenerative epithelium, showed an expanded basal zone. CONCLUSIONS: Assessment of the number of Ki-67 immunostained cells is of additional value in deciding whether the mucosa is regenerative or dysplastic, and the MIB 1 staining pattern is characteristic for most lesions with high grade dysplasia and carcinoma. Therefore, this technique could be combined with routine histological evaluation of colorectal epithelium being examined for dysplasia.  (+info)