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PubMed1992

Multiple colorectal neoplasms in a young adult with hypogammaglobulinemia. Report of a case.

We report on a 22-year-old man with congenital hypogammaglobulinemia who developed multiple colorectal neoplasms. An immunodeficiency had been diagnosed in the patient since two years of age, and this time many tumors of the sigmoid colon and rectum were detected by barium enema and fiberscopy. Abdominoperineal resection was performed, and the resected specimen revealed 29 polyps, including 9 adenocarcinomas and 20 adenomas. The carcinomas, measuring 0.8 to 11.0 cm in size, showed various depths of invasion, and the adenomas, measuring 0.2 to 1.5 cm in size, showed various degrees of epithelial atypia. DNA analysis demonstrated that the tumors were heterogeneous, showing different DNA index and ploidy patterns. The pathogenetic relation between malignancy and immunodeficiency is also reviewed.

Adenocarcinoma↗
PubMed2002

Cyclin A correlates with carcinogenesis and metastasis, and p27(kip1) correlates with lymphatic invasion, in colorectal neoplasms.

Cyclin A binds to CDK2 and plays critical roles when cells proliferate; staining for Ki67 can monitor the proliferation. The cyclin A expression pattern remains unclear in colorectal carcinogenesis and remote metastasis, however, and no one has reported on the association of its expression with key clinicopathologic factors in primary cancer. p27(kip1) protein-an extremely important inhibitor of CDK2-seems unchanged as colorectal cancers metastasize to the lymph nodes, a result contrary to that seen in gastric and prostatic cancers. To clarify the role of cyclin A in multistage colorectal neoplasms, cyclin A, CDK2, and Ki67 were immunohistochemically stained in 22 normal mucosa, 9 hyperplastic polyps, 61 adenomas, 197 primary carcinomas, 21 lymph node metastases, and 10 hepatic metastases. To clarify the alteration of p27(kip1) during lymphatic invasion, p27(kip1) was also stained in 21 primary cancers and paired lymph node foci. Situated in nuclei, cyclin A expression gradually increased from mild through moderate to severe dysplasia in adenomas and from normal tissue through hyperplasia to adenoma to early carcinoma. Expression was significantly decreased in the hepatic metastases and in the primary cancers showing venous invasion, deep infiltration, lymph node metastasis, mucinous type, advanced stage, or short postoperative survival time. Elevated cyclin A not only was linked with elevated CDK2 in primary cancers, but also was associated with increased Ki67 in both adenomas and primary carcinomas. Lymph node metastases lost more p27(kip1) than primary foci and hepatic lesions. Thus, dysregulation of cyclin A and its control mechanisms may contribute to colorectal carcinogenesis; abatement of overexpression of cyclin A is associated with hepatic metastasis and cancerous invasion. Loss of p27(kip1) may promote lymph node metastasis.

Aged↗
PubMed1999

Detection of colorectal neoplasms by the highly sensitive hemoglobin-haptoglobin complex in feces.

Screening for fecal occult blood by means of guaiac tests has an unsatisfactory sensitivity for the detection of colorectal neoplasms. The immunological determination of human hemoglobin in feces has a higher sensitivity and specificity, but hemoglobin is degraded during its transport through the gastrointestinal tract. We compared the hemoglobin test to a newly developed immuno-chemiluminometric (ILMA) assay for quantifying the hemoglobin-haptoglobin complex in feces which shows high stability against degradation. From each of 621 patients with gastrointestinal complaints before scheduled colonoscopy we collected two 1-ml samples from a single stool; there were no dietary restrictions. The sensitivity for detecting colorectal carcinomas proved 87% with hemoglobin. With the hemoglobin-haptoglobin complex it was 87% at a cutoff level of 1.5 microg/g feces, 83% at 2.0 microg/g feces, and 78% at 2.5 and 3.0 microg/g feces. The sensitivity for detecting large adenomatous polyps was 54% with hemoglobin, 76% with the hemoglobin-haptoglobin complex at a cutoff point of 1.5 microg/g feces, 73% with the hemoglobin-haptoglobin complex at 2.0 and 2.5 microg/g feces, and 65% with the hemoglobin-haptoglobin complex at 3.0 microg/g feces. The optimal cutoff point for the hemoglobin-haptoglobin complex was estimated to be 2.0 microg/g stool. The specificity for hemoglobin (99%) was significantly higher than that for the hemoglobin-haptoglobin complex at 2.0 microg/g feces (96%). Immunological determination of the hemoglobin-haptoglobin complex in feces has a comparable sensitivity as the fecal hemoglobin assay for colorectal carcinomas and a significantly higher sensitivity for adenomatous polyps but a significantly lower specificity. Its use for colorectal cancer prevention is currently being evaluated in a screening study.

Adenocarcinoma↗
PubMed1989

Association between tumor DNA aneuploidy and in vitro tetraploidy of skin fibroblasts in patients with colorectal neoplasms.

In vitro tetraploidy (IVT) in cultures of skin fibroblasts was compared with tumor DNA ploidy, as determined by flow cytometry on paraffin-embedded material, in 99 patients with colorectal neoplasm. In 63 patients with non-heritable carcinoma we found a significant correlation between the number of aneuploid stemlines in the tumor and IVT in the fibroblast culture. Furthermore, tumor aneuploidy was significantly correlated to the size of the tetraploid subpopulation in the fibroblasts. There was no correlation between aneuploidy and Dukes's stage or the degree of differentiation. In 36 patients with adenoma no correlation between tumor aneuploidy and fibroblast IVT was demonstrated, whereas the number of tumor stemlines was significantly correlated to histopathologic stage and grade of dysplasia. IVT in cultured skin fibroblasts, which has been reported to reflect a genetic predisposition to colorectal cancer in heritable colon cancer syndromes, thus seems to be relevant also for the understanding of tumor formation and progression in the 'non-heritable' type of colorectal cancer.

Adenoma↗
PubMed1990

Double contrast barium enema and flexible rectosigmoidoscopy: a reliable diagnostic combination for detection of colorectal neoplasm.

The efficiency of double contrast barium enema and flexible rectosigmoidoscopy (to 60 cm) in the assessment of patients with a positive Hemoccult II test in a randomized screening study for colorectal neoplasms was evaluated. A positive test was present in 625 patients, of whom 530 had a complete enema and rectosigmoidoscopic assessment. A carcinoma was diagnosed in 26 and an adenoma greater than or equal to 1 cm in diameter in 71. As a control, 323 patients with a negative assessment repeated the Hemoccult II test and of these 67 had a positive second test, of whom 55 underwent colonoscopy. One carcinoma (Dukes' A) and two adenomas greater than or equal to 1 cm in diameter were diagnosed. The efficiency of the assessment was also checked by rescreening the whole group 1-2 years after the first study and by continuing follow-up. It was found that two more carcinomas and one adenoma greater than or equal to 1 cm in diameter had been overlooked at the primary assessment. The sensitivity for neoplasms greater than or equal to 1 cm in diameter at the primary assessment was 72 per cent for double contrast barium enema and 86 per cent for rectosigmoidoscopy. The sensitivity for the combined methods was 94 per cent and the specificity was 99 per cent. The combination of double contrast barium enema and rectosigmoidoscopy in the primary assessment of patients with a positive Hemoccult II test gives an acceptable result and immediate retesting of those with a negative assessment is not necessary.

Adenoma↗
PubMed2006

Association of metabolic syndrome with proximal and synchronous colorectal neoplasm.

BACKGROUND & AIMS: Metabolic syndrome and its associated morbidities have become a major public health problem in both developed and developing countries. Insulin resistance, the core mechanism of metabolic syndrome, has been associated with the development of colorectal neoplasm, but the interrelation between metabolic syndrome and colon cancer is rarely addressed. Our study aimed to determine whether metabolic syndrome is associated with the risk and clinical presentation of colorectal neoplasia. METHODS: Consecutive 4277 ethnic Chinese who received complete total colonoscopy and thorough health checkups were enrolled. Both National Cholesterol Education Program's Adult Treatment Panel III and modified Asian criteria were used for defining metabolic syndrome. Logistic regression modeling was used to elucidate the association between colorectal neoplasia and metabolic syndrome. The impact of metabolic syndrome on distribution and number of colorectal neoplasia was also assessed. RESULTS: Of all those enrolled, 27.1% of men and 18.9% of women met the criteria of metabolic syndrome, and 9.8% had colorectal neoplasia. Metabolic syndrome was associated with odds ratio (OR) of 1.35 (95% confidence interval [CI], 1.05-1.73) for colorectal neoplasia. OR was 0.96 (95% CI, 0.67-1.38) for distal lesions, 1.62 (95% CI, 1.14-2.30) for proximal lesions, 2.15 (95% CI, 1.40-3.31) for synchronous lesions, and 2.30 (95% CI, 1.42-3.72) for synchronous lesions located at both sides of colon. CONCLUSIONS: Subjects with metabolic syndrome have a higher risk of colon neoplasia at the proximal colon and synchronous lesions at both sides of the colon. These findings will help future colon cancer screening and prevention in patients with metabolic syndrome.

Adult↗
PubMedDate not supplied

[Colorectal neoplasms in patients with ulcerative rectocolitis. Their surgical treatment and follow-up].

Patients with ulcerative colitis (UC), especially those with a long-term standing or severe disease, show a higher incidence of colorectal neoplasms. Dysplasia represents the most important risk-factor for malignancy in patients with UC. From 1989 to 1999, 71 patients with UC, were surgically treated at our Institution. Indications for surgery were: non responding disease or refractory bleeding in 61; pathologic evidence of severe dysplasia during endoscopic surveillance in 5 patients, evidence of a neoplasm in the remaining 5 patients. Operative mortality was 1.4%. Infections of the surgical wound has been the most common postoperative complication. In 4 cases pouchitis has been reported. In 7 patients because of progression of the proctitis a second surgical treatment has been made. When surgical treatment is indicated in the course of ulcerative colitis, several operations may be performed. In the large majority of patients, total colectomy, mucosectomy and ileal pouch-anal anastomosis is the procedure of choice.

Adenocarcinoma↗
PubMedDate not supplied

Evaluation of the risk for metachronous colorectal neoplasms following intestinal polypectomy: a clinical, endoscopic and pathological study.

BACKGROUND/AIMS: Surveillance programs are recommended for patients with previous intestinal polypectomy because of the high rate of adenomatous recurrences and risk of subsequent colorectal cancer. The parameters to identify patients at higher risk and the length and schedules of follow-up have not yet been established. We considered some clinical, endoscopic and pathological parameters in order to assess the probability of developing new colorectal neoplasms and eventually to schedule proper surveillance programs. METHODOLOGY: Patients with removed adenomas were enrolled into a clinico-endoscopic follow-up, comprehensive of two colonoscopies the first at 1 year and the second at 3 years. We evaluated the risk of new neoplasms dividing the patients into four groups according to the number and size of the adenomas removed and the parameters considered. RESULTS: Of 164 patients enrolled 156 completed the study. We had an overall 21.3% of adenomatous recurrences at 1 year and 12.8% at 3 years. Most of the adenomas removed were tubular and small in size (< 1 cm). The percentage of patients who had adenomas with advanced pathological features was 1.82% at 1 year and 0.64% at 3 years. The increase in number and size of the adenomas removed on the initial colonoscopic examination was the only one parameter statistically significant, X(2)1 (trend) 5.11; p<0.05 at the first follow-up and X(2)1 (trend) 4.87; p<0.05 at the second follow-up. CONCLUSIONS: Patients with previous single adenoma showed few recurrences of extremely benign histological features. Since they do not require short-term endoscopic examination, it would be reasonable to defer the next colonoscopy for at least another 5 years. During follow-up, patients with multiple polyps had adenomas with advanced pathological features so it was useful to follow-up at 1 year. The tendency for advanced pathological features of removed polyps was not seen at 3 years, suggesting the importance of long-term follow-up, but with longer intervals.

Adenoma↗
PubMed2000

Preoperative evaluation of colorectal neoplasms by colonoscopic miniprobe ultrasonography.

OBJECTIVE: To investigate the value of colonoscopic miniprobe ultrasonography for preoperative staging of colorectal neoplasms. SUMMARY BACKGROUND DATA: Endoscopic ultrasonography is the most accurate technique for staging colorectal cancer. However, limitations of this technique include the inability to examine stenotic tumors and the difficulty of reaching tumors proximal to the rectum. METHODS: Miniprobe ultrasonography (12.5 MHz) was performed in 63 patients with tumors of the colon or rectum. The results of imaging were compared with endoscopic assessment of the lesions and histopathologic findings of the resected specimens. RESULTS: Miniprobe ultrasonography allowed high-resolution imaging of colorectal tumors during routine colonoscopy. The infiltration depth was correctly classified in 22 adenoma, 3 T1, 10 T2, and 22 T3 or T4 tumors. The accuracy for tumors of the rectum and colon was 86% and 92%, respectively (overall accuracy 90%). The small diameter of the probe allowed examination of 21 stenotic tumors with an accuracy of 86%. Miniprobe ultrasonography revealed carcinoma in 5 of 30 broad-based polyps, although adenomas were diagnosed by endoscopy. Correct assessment of lymph node involvement was obtained in 47 of 55 patients. Based on the findings of miniprobe ultrasonography, management was modified in 7 of the 63 patients. CONCLUSIONS: These preliminary results show that miniprobe ultrasonography improves preoperative staging of stenotic rectal cancer and colonic tumors. This technique can be easily performed during routine colonoscopy and may have considerable impact on surgical therapy.

Adult↗
PubMed2002

Loss of heterozygosity in the clonal evolution of flat colorectal neoplasms.

In contrast to invasive colorectal carcinomas that develop in typical exophytic adenoma-carcinoma sequences, some invasive cancers may evolve from flat mucosal dysplastic lesions. Despite their relatively small size, these flat colorectal lesions are often associated with high-grade dysplasia and may show an aggressive clinical course. To delineate the genetic pathways in the clonal evolution of these tumors, multiple foci were microdissected from 13 cases and the allelic deletions of 15 chromosomal arms were analysed. Loss of heterozygosity (LOH) was detected most frequently on 17p (77%), followed by 18q (69%), and 5q (54%). In five cases with concomitant low-grade adenomas, only one case showed LOH in low-grade adenoma foci. In high-grade dysplasia with/without submucosal invasion, early and homogeneous LOH of one to several chromosomal arms was detected. Overall, homogeneous and thus early LOH were most frequently detected on 17p (seven of 10 cases with 17p LOH), followed by 3p (two of three cases with 3p LOH), and 5q (four of seven cases with 5q LOH). In addition to homogeneous LOH, the LOH patterns observed in different portions of dysplasias and invasive cancers in individual cases identified several different genetic patterns of tumour progression, either with linear or branching (divergent) trees. Positive immunostaining for p53 was detected in 10 of the 13 cases; of these, five cases were concomitant with 17p LOH in all of the microdissected foci, four cases were concomitant with 17p LOH in a majority of foci and, one case showed retention of 17p. Except for the flat configuration and early 17p LOH, genetic heterogeneity in the flat high-grade dysplastic foci was found to be similar to genetic chaos in the late dysplastic and preinvasive stages of exophytic adenoma. These findings suggest a potentially aggressive course for these neoplasms.

Adenoma↗
PubMed1997

CT colonoscopy of colorectal neoplasms: two-dimensional and three-dimensional virtual-reality techniques with colonoscopic correlation.

OBJECTIVE: The aim of this study was to compare the diagnostic accuracy of two-dimensional (2D) CT colonography and three-dimensional (3D) virtual colonoscopy with conventional colonoscopy in patients who have suspected colorectal neoplasms. SUBJECTS AND METHODS: Twenty patients were studied (eight women and 12 men; mean age, 53 years; range, 42-85 years). All patients had findings on conventional colonoscopy suggestive of colorectal carcinoma and underwent colonic CT within 3 hr of endoscopy. Two-dimensional CT colonography and 3D virtual colonoscopy images were generated from the same data set that was obtained from thin-section helical CT of the abdomen and pelvis after rectal insufflation of room air. Three-dimensional virtual colonoscopy images were obtained by downloading CT data to a workstation equipped with commercially available software. Volume- and perspective-rendering techniques were used to achieve interactive, 3D virtual "fly-through" examinations of the colonic mucosa. The results of 2D CT colonography and 3D virtual colonoscopy were compared with the findings of conventional colonoscopy and correlated with surgical and pathologic outcome where possible. RESULTS: Twenty masses (defined as intraluminal projections 2 cm or larger in diameter) and 15 polyps (defined as projections smaller than 2 cm in diameter) were identified in our study group. All masses and 14 of 15 polyps were successfully shown on 2D colonography. Three findings of polyps on 2D colonography were false-positive, and one was false-negative. Three-dimensional virtual colonoscopy revealed 19 of 20 masses and 13 of 15 polyps. On conventional colonoscopy, all 20 masses and 13 of 15 polyps were identified, with one false-positive finding of a malignant stricture in a normal colon. Complete examination of the colon was possible in 18 of 20 patients using the 2D technique and in 17 of 20 patients using 3D virtual colonoscopy, whereas conventional colonoscopy showed the entire colon in only 12 of 20 patients. CONCLUSION: Two-dimensional CT colonography and 3D virtual colonoscopy are complementary and effective techniques for examining the colon in patients with suspected colorectal carcinoma. CT techniques offer several advantages over conventional colonoscopy including the ability to detect abnormalities proximal to obstructing carcinomas, accurate localization of abnormalities within the colon, and good patient tolerance. These CT techniques may play an important role in future diagnosis of colorectal cancer and for screening patients at risk.

Colonic Polyps↗
PubMed2005

Expression of phosphorylated Ser70 of Bcl-2 correlates with malignancy in human colorectal neoplasms.

PURPOSE: Bcl-2 is a model apoptosis suppressor postulated to promote tumorigenesis. Recently, it has been reported that Bcl-2 undergoes phosphoregulation of its Ser70 to substantially alter its molecular function. Previous studies further suggest that such phospho-Bcl-2 regulation may influence tumor progression in colorectal and other cancers; however, phosphorylation status of the Ser70 of Bcl-2 (pSer70) in vivo in tumors remains obscure. To elucidate this question that may suggest the biological role, we molecularly screened a panel of human colorectal adenomas and adenocarcinomas for endogenous expression of pSer70 Bcl-2. EXPERIMENTAL DESIGN: An antibody specific against pSer70 Bcl-2 was generated for thorough immunohistochemical examination of paraffin-embedded tumor specimens, allowing detection of the endogenously expressed antigen among a range of Bcl-2-positive colorectal neoplasms, including 75 tubular adenomas, 114 adenocarcinomas, and 15 cases of cancer in adenomas. RESULTS: Loss of pSer70 Bcl-2 expression was observed in adenocarcinomas in a differentiation-dependent manner (positivities: well differentiated 63%, moderately differentiated 52%, and poorly differentiated 12%), whereas tubular adenomas maintained their expression (positivity 88%). Interestingly, an inverse correlation was found between expression of pSer70 Bcl-2 and Ki-67 antigen in those cases of cancer in adenoma (P < 0.01). It was further observed that loss of pSer70 Bcl-2 expression was associated with significantly shorter survival (P < 0.05) and correlated with clinical stages and lymph node metastasis (P < 0.05 and P < 0.05, respectively). CONCLUSIONS: Loss of pSer70 Bcl-2 expression is closely linked to biological aggressiveness in colorectal tumors and represents a statistically significant molecular index for prognosis of patients with these tumors.

Adenocarcinoma↗
PubMed1997

Activation of the K-ras oncogene in colorectal neoplasms is associated with decreased apoptosis.

BACKGROUND: Recent in vitro data indicate that the oncogenic effects of activated ras genes may be mediated, at least in part, through inhibition of apoptotic cell death. To examine this proposition in vivo, the relationship between mutations of the K-ras gene and the frequency of apoptosis was studied in a series of 69 sporadic colorectal neoplasms (11 adenomas and 58 carcinomas). METHODS: Mutations in codon 12 of K-ras were determined by a single tube, enriched polymerase chain reaction. Apoptotic cells in tumor sections were identified by in situ end-labeling of fragmented DNA, whereas levels of bcl-2 and p53 proteins were determined by immunohistochemistry. RESULTS: Tumors with mutant K-ras had a significantly lower apoptotic index than those with the wild-type allele (P < 0.05). They were also more likely to exhibit positive bcl-2 staining (P < 0.05). Adenomas showed significantly greater bcl-2 positivity than carcinomas (89% and 51%, respectively; P < 0.05). The frequency of apoptosis in these tumors was not related to either bcl-2 positivity or p53 status. CONCLUSIONS: These findings suggest that activation of K-ras in colorectal carcinoma may inhibit apoptosis and thus favor tumor progression. Alternatively, this association may reflect an accumulation of K-ras mutations in cells in which normal apoptotic pathways have been impaired.

Adenoma↗
PubMed2000

[Melatonin and serotonin in inflammatory colon diseases and colorectal neoplasms].

Patients with inflammatory intestinal diseases and colorectal adenocarcinoma in sigmoid mucosa were examined using light and electron microscopy, immunohistochemical tests, radioimmunoassay and morphometry. Functional morphology of the general population of the endocrine cells and apudocytes producing melatonin and serotonin as well as urine excretion of 6-sulfatoxymelatonin changed in quality and quantity. The parameters showed specificity depending on clinicomorphological variant of colorectal pathology. The findings provide additional criteria in diagnosis and prediction of the course of different types of inflammatory and tumor affections of the colon.

APUD Cells↗
PubMed2001

Expression of lysosome-associated membrane proteins in human colorectal neoplasms and inflammatory diseases.

The lysosome-associated membrane proteins (LAMPs)-1 and -2 are major constituents of the lysosomal membrane. These molecules are known to be among the most glycosylated proteins of several types of cells and cancer cells, and their expression in cancer cells is marked by a distinct difference in the structures of the oligosaccharides as compared to nonmalignant cells. We analyzed by immunohistochemistry the intensity and distribution of LAMP-1 and LAMP-2 in 9 human colorectal cancer cases and in 16 control cases, including inflammatory diseases (diverticulitis, ulcerative colitis, and Crohn's disease). LAMP proteins were expressed more intensely in the epithelium of colorectal neoplasms than in normal mucosa (P < 0.05), and no significant differences were found between adenoma and cancer cells (P > 0.05) in the same tissue section. Further, in sites of inactive inflammatory diseases and nonneoplastic areas in cancer specimens, no significant increases in epithelial LAMP proteins were observed, even in the proliferative zone of the lower crypt epithelium. Northern blot analysis showed increased expression of LAMP-1 and LAMP-2A in two of three colorectal cancers examined and increased LAMP-2B in all three cancers. Our findings suggest that LAMPs are related to neoplastic progression, but there is no direct association between the expression of LAMP molecules and cell proliferation.

Adenocarcinoma↗
PubMed2005

Risk of colorectal neoplasm in patients with acromegaly and its relationship with serum growth hormone levels.

OBJECTIVES: Acromegalics have been reported to be at an increased risk of colorectal neoplasm. However, the magnitude of the risk is still controversial and the mechanism has not been fully investigated. In this study, we attempted to determine the magnitude of the association between acromegaly and colorectal lesions after taking into account age, gender, smoking status, and treatment status. In addition, we assessed the relationship between colorectal lesions and serum growth hormone (GH) levels in acromegalics. METHODS: We conducted a case-control study by using 19 consecutive untreated patients (male:female = 11:8) who were newly diagnosed with acromegaly between 1990 and 2000. All patients underwent colonoscopy and received a histological diagnosis of colorectal lesions. Prevalence of hyperplastic polyp, adenoma, and carcinoma were compared with the prevalence in 76 controls matched for gender, age, and smoking status. Serum GH levels were compared between acromegalic patients with and without each type of colorectal lesion. RESULTS: The prevalence of hyperplastic polyp, adenoma, and carcinoma were significantly higher in the acromegalic patients compared to the controls (p < 0.05, odds ratios; 8.3, 4.2, and 9.8, respectively). In acromegalics, the presence of hyperplastic polyps and carcinomas were significantly associated with higher serum GH levels after adjusting for the other lesions and age (p < 0.05). CONCLUSIONS: After controlling for age, gender, smoking status, and treatment status, acromegaly was associated with significantly higher prevalence of colorectal hyperplastic polyp, adenoma, and carcinoma. High serum GH levels may be associated with the presence of hyperplastic polyp and carcinoma.

Acromegaly↗
PubMed1985

Immunohistochemical detection of the ras oncogene p21 product in an experimental tumour and in human colorectal neoplasms.

The monoclonal antibody Y13 259 to the ras oncogene protein product p21 was used in an immunohistochemical study of ras expression in human colorectal neoplasms. The ability of the antibody to detect enhanced levels of ras expression was confirmed by its use with an experimental neoplasm known to express ras at high levels. Human colonic adenocarcinomas in general showed a similar staining intensity to that seen in normal mucosa. Adenomas however showed consistently high p21 expression as indicated by staining intensity. This suggests that elevated ras expression may be important in the development of adenomas, but that high levels need not be sustained in the conversion to invasive carcinoma.

Adenocarcinoma↗