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PubMed1994

Application of the crypt-isolation technique to flow-cytometric analysis of DNA content in colorectal neoplasms.

BACKGROUND/AIMS: Conventional flow-cytometric analysis of colorectal tumor DNA content includes both tumor and stromal cell DNA. To improve the method, we evaluated the DNA content of purified epithelial cells using the crypt-isolation technique. METHODS: Normal and neoplastic crypts were isolated from fresh resected colorectum nonenzymatically. Isolated crypts were digested into single nuclei suspensions and examined by flow cytometry (FCM). Internal controls from normal crypts were used to define diploidy. The neoplastic nuclei in the same individual and mixtures of both normal and neoplastic nuclei in various ratios were analyzed. RESULTS: Tumors having both diploid and aneuploid stemlines were found more frequently than that reported using conventional FCM. Near-diploid DNA stemlines with DNA indices ranging between 0.90 and 1.10 were detectable. The cases of advanced cancer in which the DNA index was between 0.90 and 0.95 were associated significantly with Dukes' stage C. CONCLUSIONS: This is the first reported analysis of the DNA content of "pure" neoplastic colorectal epithelia using FCM. Multiploid and near-diploid stemlines were more accurately analyzed than that using conventional FCM.

Adenocarcinoma↗
PubMed1996

Alterations of transforming growth factor-beta 1 receptor type II occur in ulcerative colitis-associated carcinomas, sporadic colorectal neoplasms, and esophageal carcinomas, but not in gastric neoplasms.

BACKGROUND & AIMS: Gastric cancers, sporadic colorectal cancers, and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias manifest microsatellite instability (MI); however, esophageal carcinomas rarely exhibit MI. Recently, a transforming growth factor-beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in primary colorectal carcinomas demonstrating MI. No previous studies of TGF-beta 1RII have addressed mechanisms of inactivation other than MI in human tumors; furthermore, MI-negative tumors have not been examined for TGF-beta 1RII mutation. We evaluated 138 primary human neoplasms for mutation in the poly-A microsatellite tract of TGF-beta 1RII. Additionally, a group of esophageal tumors was evaluated for the expression of TGF-beta 1RII messenger RNA (mRNA). METHODS: First, we determined whether MI was present at other chromosomal loci in these lesions. The poly-deoxyadenine (poly-A) microsatellite tract within the TGF-beta 1RII coding region was then PCR-amplified. In a group of MI-negative esophageal tumors, RT-PCR was performed to determine the expression of TGF-beta 1RII mRNA. RESULTS: Among 17 MI+ UC specimens, 3 (18%) demonstrated TGF-beta 1RII poly-A tract mutation (2 cancers and 1 dysplasia), while 2 (4%) of 44 MI-negative UC specimens (1 dysplasia and 1 tumor), and 13 (81%) of 16 MI+ sporadic colorectal cancers, contained TGF-beta 1RII poly-A mutation. No gastric or esophageal tumors contained TGF-beta 1RII mutation. Among 21 MI-negative esophageal carcinomas. 6 cases (28.5%) had TGF-beta 1RII transcripts that were low or undetectable by RT-PCR. CONCLUSIONS: Mutation within the poly-A microsatellite tract of TGF-beta 1RII occurs early in a subset of UC-neoplasms and commonly in sporadic colorectal cancers, but may be rare in MI+ gastric tumors. Diminished expression of TGF-beta 1RII mRNA in esophageal tumors suggests that mechanisms of inactivation in this gene other than MI play a role in esophageal carcinogenesis.

Colitis, Ulcerative↗
PubMed1995

Colorectal neoplasms. Screening can save lives.

Colorectal cancer is a very important cause of death and disability throughout the world. In the future, it may be possible to reduce the risk of this disease through such measures as dietary modification or use of aspirin or other nonsteroidal anti-inflammatory drugs, but this remains to be proved. It may also be possible to detect persons at high risk or those with early lesions by using noninvasive studies, such as genetic tests or detection of trace markers in the stool, but these approaches either are not yet available or are not proved in clinical trials. However, through careful and systematic clinical history taking and appropriate screening studies, neoplasms can be detected early or in the precancerous stage. Mortality from colon cancer could be reduced dramatically by applying currently available methods as part of a health maintenance program. Fecal occult blood testing and flexible sigmoidoscopy must be integrated into practice routines in the same way that Pap smears and mammography have been accepted by physicians and patients as a way to save lives.

Adenocarcinoma↗
PubMed1999

Prognostic evaluation of metallothionein expression in human colorectal neoplasms.

AIM: To investigate the role of metallothionein in colorectal tumours and the possible relation with other factors associated with tumour progression: expression of cathepsin D (CD), CD44, p53, Rb, bcl-2, c-erbB-2, epidermal growth factor receptor (EGFR), proliferation indices (Ki-67, proliferating cell nuclear antigen (PCNA)), and conventional clinicopathological variables. METHODS: The immunohistochemical expression of metallothionein was investigated in 23 cases of colorectal adenoma and 94 adenocarcinomas. Metallothionein expression was examined by the avidinbiotin peroxidase immunoperoxidase (ABC) using the monoclonal mouse antibody E9, on formalin fixed, paraffin embedded tissue. RESULTS: Positive metallothionein expression (> 5% of neoplastic cells) was observed in 30.4% of adenomas and 25.5% of adenocarcinomas, while 8.7% of adenomas and 14.9% carcinomas showed focal metallothionein positivity. In contrast, 60.9% of adenomas and 59.6% of carcinomas almost completely lacked metallothionein expression. In the series of adenocarcinomas, metallothionein expression was inversely correlated with CD44 in neoplastic cells (p = 0.01). There was no statistically significant difference of metallothionein expression, or the other variables examined, between adenocarcinomas and adenomas. CONCLUSIONS: Metallothionein expression does not seem to indicate aggressive biological behaviour in colorectal adenocarcinomas, in comparison with the other types of carcinoma. The inverse correlation with CD44 could suggest that the decreased metallothionein expression may contribute to the metastatic spread of the lymph node involvement in colorectal cancer. Metallothionein expression does not seem to represent an independent prognostic marker in colorectal cancer.

Adenocarcinoma↗
PubMed2001

[Prognostic factors in colorectal neoplasm. Multivariate analysis in 224 patients].

BACKGROUND: Staging of colorectal carcinoma has prognostic value and allows to take decisions about adjuvant therapy and follow up. Prognostic factors are not universally accepted and there are different staging classifications. AIM: To assess the prognostic value of clinical and pathological variables in 224 patients subjected to a curative resection of a colorectal carcinoma. PATIENTS AND METHODS: A retrospective analysis of 99 men and 125 women, aged 23 to 91 years old subjected to a curative resection of a colorectal carcinoma and followed up for a mean of 72 months. RESULTS: Global survival at 60 months was 72%. Univariate analysis showed that tumor localization, vascular permeation, wall infiltration and number of involved lymph nodes had an influence on survival. A Cox regression model disclosed tumor localization (colon versus rectum), a carcino-embryonic antigen over 30 ng/ml, vascular permeation, presence of 1 to 4 involved lymph nodes, or 5 or more lymph nodes and the presence of an apical lymph node as variables with significant prognostic value. CONCLUSIONS: Our series confirms the prognostic importance of lymph node involvement. This parameter is incorporated in Jass, GITSG (both modifications of Dukes classIfication) and TNM staging scores.

Adenocarcinoma↗
PubMed2006

Cytokeratin 7/20 and mucin core protein expression in ulcerative colitis-associated colorectal neoplasms.

Different histogenetic pathways have been suggested between ulcerative colitis (UC)-associated neoplasia and sporadic colorectal neoplasia. Little is known about the cytokeratin (CK) and mucin expression in UC-associated neoplasms. To clarify the characteristics of UC-associated colorectal carcinogenesis, we examined the immunohistochemical expression of CK7, CK20, MUC2, MUC5AC and MUC6 in 90 colorectal neoplasms, including 22 UC-associated adenocarcinomas (colitic cancer; CC), ten high-grade dysplasias (HGD) in UC, nine low-grade dysplasias (LGD) in UC, 24 sporadic tubular adenomas (TA) and 25 adenocarcinomas (AC). CK7 was positive in most of UC-associated neoplasms: 59% of CC cases, 80% of HGD and 89% of LGD, respectively, whereas, in non-UC associated neoplasia, 21% of TA and 12% of AC. The frequency of MUC6 expression in UC-associated neoplasia was 32% in CC, 30% in HGD and 44% in LGD, respectively, whereas, in non-UC associated neoplasia, 4.2% in TA and 0% in AC. MUC5AC expression in UC-associated neoplasia was detectable in 73% of CC, 90% of HGD and 89% of LGD, respectively; in non-UC associated neoplasia 67% in AC and 20% in TA. There were obvious differences in the expression of CK7 and MUC6 between UC-associated neoplasms and sporadic tumors. The incidence of MUC5AC expression in UC-associated neoplasms was also higher than sporadic tumors. These results suggest that gastric-type mucins play an important role in the initial step of CC-tumorigenesis, and CK7 and gastric-type mucins may be useful in the differential diagnosis between UC-associated neoplasms and sporadic ones.

Adenocarcinoma↗
PubMed1981

Hemoccult II test: routine screening procedure for colorectal neoplasm?

In October, 1978, the Hemoccult II Test was introduced as a screening procedure by the Sydney Hospital Heath Information and Screening Service. In the first two years, 4498 people were screened and 150 positive results were obtained. These people were referred for further investigation, with 114 choosing to attend the Edward Wilson Colon and Rectum Unit outpatient clinic at Sydney Hospital. Forty-four patients were found to have 59 colorectal neoplasms of which 13 were carcinomas. This represents a cancer incidence of 0.29% and corroborates the results of similar studies conducted overseas.

Australia↗
PubMed1998

[A role for cryosurgery in the treatment of non-resectable liver metastases of colorectal neoplasms].

Liver metastases occur in over 40% of patients with colorectal carcinomas. The best prospect of cure is achieved by resection of the metastases. However, only 10-15% of the patients with hepatic metastases are estimated to be candidates for resection. When curative resection cannot be performed the options for treatment are limited. Response rates to chemotherapy are around 40% and even then survival benefit is generally limited to a few months. Hepatic cryosurgery recently provided a new therapeutic approach for unresectable liver metastases. For cryosurgery tumour tissue is located by ultrasonography and then cooled by liquid nitrogen to a temperature of -196 degrees C, which results in necrosis of tumour tissue. In a limited number of series encouraging results of cryosurgery have been reported. One year and two year survival rates of respectively 70% and 50% were reported after cryosurgery for hepatic metastases. Disease free survival rate after 2 years varies from 20% to 28%. If recurrence of the disease occurred in the liver it was generally outside the areas treated by cryosurgery. Benefit in survival is only achieved when all tumour tissue is treated adequately. Hepatic cryosurgery is appropriate in those patients with unresectable metastatic disease in whom cryosurgery alone or in combination with resection is able to eradicate all metastatic disease in the liver.

Antineoplastic Agents↗
PubMed1979

Colorectal neoplasm: a rare complication of ureterosigmoidostomy.

A 24-year-old woman had a rectal neoplasm which occurred 20 years after she had undergone ureterosigmoidostomy for exstrophy of the bladder. Only 41 cases of bening or malignant tumours of the large bowel developing after ureterosigmoidostomy have previously been reported in the literature. Adenocarcinoma of the colon is most frequently found and can develop even after urine has been diverted away from the colon. The presenting symptoms are either those of ureteral obstruction or of colorectal neoplasm. This rare complication remains intriguing and the possible pathogenetic mechanisms are discussed.

Adult↗
PubMed2002

Down-regulation of drs mRNA in colorectal neoplasms.

The drs gene was originally isolated as a transformation suppressor gene against the v-src oncogene. Expression of drs mRNA is down-regulated by retroviral oncogenes such as v-src and v-K-ras in the rat cell line F2408. Expression of drs mRNA is also markedly reduced in a variety of human cancer cell lines, including those of carcinomas of the colon, bladder, and ovary, suggesting that down-regulation of drs mRNA is correlated with the development of human cancers. To clarify the correlation between down-regulation of the drs gene and malignant tumor formation in human colorectal neoplasms, we examined expression of drs mRNA in a variety of colon cancer tissues by in situ hybridization. A total of 53 morphologically distinct neoplastic specimens were divided into the following five groups according to morphology: low and high grade adenoma in 7 and 12 cases, respectively (groups A, B), protruded-type carcinoma in 16 (group C), superficial-type carcinoma with an adenomatous component in 10 (group D) or superficial-type carcinomas without any adenomatous component in 8 (group E). Expression of drs mRNA was detected in normal mucosa, low-grade adenoma and most superficial-type carcinomas without any adenomatous component. On the other hand, the rate of drs mRNA expression was significantly lower in protruded-type adenocarcinoma and superficial-type carcinoma with an adenomatous component. Our results indicate that down-regulation of drs mRNA is closely correlated with carcinomas which arise from adenomatous polyps in the course of the adenoma-carcinoma sequence, but that most carcinomas arising de novo are independent of the tumor suppressor function of the drs gene.

Adenoma↗
PubMedDate not supplied

[Clinical-experimental models for the identification of immunologic parameters to be integrated in traditional staging systems of colorectal neoplasms].

The Authors evaluate new possible models for the staging of colorectal cancer based on clinico-morphological, histo-pathological and bio-immunological parameters. Particularly, they evaluate the possibility of studying host's immunological response against tumor spread by the examination of the "in situ" cellular responses. This study was performed by cytotoxic test and immunohistochemical evaluation of the lymphocytes. The latter seems to give better results compared to the first in the evaluation of the host's immunological response.

Colorectal Neoplasms↗
PubMed1995

1,25-Dihydroxyvitamin D3 and retinoid X receptor expression in human colorectal neoplasms.

Epidemiological studies suggest that 1,25-dihydroxyvitamin D3 (D3) protects against colorectal carcinogenesis. Animal and in vitro studies show an antiproliferative effect of D3 in a variety of tumours including those of large bowel origin. D3 actions are mediated by D3 receptors (VDR) alone or by VDR in conjunction with retinoid X receptors (RXRs) in all D3 responsive tissues. The expression of mRNAs encoding VDR and RXRs in normal and malignant human colorectum was determined. Full length VDR (4.6 kB), RXR alpha (5.5 kB), and RXR gamma (3.5 and 7 kB) mRNAs were expressed in all tissues, but RXR beta mRNA was not expressed in any. VDR expression was reduced in 12 carcinomas relative to paired normal mucosa, and RXR alpha expression was reduced in nine. There was no correlation between VDR or RXR alpha expression and the site, grade of differentiation, or Dukes's staging of the tumour. The finding of persistent VDR and RXR coexpression in all colorectal tumours provides a rational basis for exploring a role for D3 in the treatment of colorectal malignancy.

Blotting, Northern↗
PubMed1996

[Detection of liver metastases in colorectal neoplasms: use of intraoperative echography].

Fifty patients were consecutively operated on for colorectal cancer. Preoperative ultrasonography and intraoperative palpation were compared to intraoperative ultrasonography to determine their relative capacities in the detection of liver metastases. Preoperative ultrasonography detected metastases in three patients (6%), intraoperative palpation in four (8%) and intraoperative ultrasonography in 5 (10%). The number of metastases detected were 7, 19 and 19 respectively. The comparison failed to yield significant differences. From statistical viewpoint, both preoperative ultrasonography and intraoperative palpation were found to be as effective as intraoperative ultrasonography in detecting liver metastases.

Aged↗
PubMed1986

Colorectal neoplasms and Barrett's esophagus.

Prospective colonoscopic study of 36 patients with Barrett's esophagus found colorectal adenomas in 33% of patients. Of patients aged less than 60, four of 17 (24%) had adenomas, while patients aged 60 or more had adenomas in eight of 19 (42%) cases. All adenomas were less than or equal to 10 mm diameter. No colorectal malignancies were found in these patients. This prevalence of neoplasms is consistent with results of autopsy studies. It is concluded that no increased risk of colorectal neoplasms was found in this group of patients with Barrett's esophagus.

Adenoma↗
PubMedDate not supplied

[Intestinal obstruction caused by colorectal neoplasms].

The Authors report their ten-year experience in 85 cases of colorectal carcinoma presenting with large bowel obstruction. They underline the high morbidity and mortality of such condition related to the late diagnosis and the poor general conditions of the patients. After reviewing the literature they point out that the best treatment consists in dealing both with the intestinal obstruction and its cause during the same operative time. The post-operative mortality after radical treatment is acceptable especially when compared to derivative procedures.

Adult↗