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C M Fenoglio-Preiser

Publications and source records attributed to C M Fenoglio-Preiser.

At least 19 recordsLinked to original sources
PubMed2000

American Joint Committee on Cancer Prognostic Factors Consensus Conference: Colorectal Working Group.

BACKGROUND: The American Joint Committee on Cancer (AJCC), which regularly reviews TNM staging systems, established a working party to develop recommendations for colorectal carcinoma. METHODS: A multidisciplinary consensus conference using published literature developed an arbitrary classification system of prognostic marker value (Category I, IIA, IIB, III, and IV), which forms the framework for this report. RESULTS: The working party concluded that several T categories should be subdivided: pTis into intraepithelial carcinoma (pTie) and intramucosal carcinoma (pTim); pT1 into pT1a and pT1b corresponding to the absence or presence of blood or lymphatic vessel invasion, respectively; and pT4 into pT4a and pT4b according to the absence or presence of tumor involving the surface of the specimen, respectively. The working party also recommended that TNM groups be stratified based on the presence or absence of elevated serum levels of carcinoembryonic antigen (CEA) (>/= 5 ng/mL) on preoperative clinical examination. In addition, the working party also concluded that carcinoma of the appendix should be excluded from the colorectal carcinoma staging system because of fundamental differences in natural history. CONCLUSIONS: The TNM categories and stage groupings for colorectal carcinoma published in the current AJCC manual have clinical and academic value. However, a few categories require subdivision to provide increasing discrimination for individual patients. The serum marker CEA should be added to the staging system, whereas multiple other factors should be recorded as part of good clinical practice. Although many molecular and oncogenic markers show promise to supplement or modify the current staging systems eventually, to the authors' knowledge none have yet been evaluated sufficiently to recommend their inclusion in the TNM system.

Adenocarcinoma↗
PubMed2000

Microsatellite instability and K-ras mutations in patients with ulcerative colitis.

Patients with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), have an increased incidence of colorectal carcinoma. The underlying mechanism is unknown, but we postulated that microsatellite instability (MSI) might predispose the colonic mucosa of UC patients to mutations, thereby increasing their cancer risk. We also sought to determine the frequency of K-ras mutations, to determine whether MSI predisposed to K-ras mutations and to compare the molecular phenotype of biopsy and resection specimens in the same patient. We also sought to determine whether molecular alterations found in biopsy specimens presaged their presence in subsequent resection specimens. Two hundred fifty-eight specimens from 52 patients were examined for K-ras mutations by direct sequencing. Seventy-one of the specimens were neoplastic. MSI was evaluated after polymerase chain reaction (PCR) amplification using primers directed at 8 microsatellite loci. Of the patients, 18.2% had K-ras mutations, and 30.8% had MSI in at least 1 locus. Of K-ras mutations, 81.8% were G to A substitutions involving the second nucleotide of codons 12 or 13. Only 0.7% of the samples showed a high level of MSI. No relationship existed between MSI and K-ras mutations, even in the 2 samples with high-level MSI. The numbers are small, but it appeared that MSI in biopsies failed to predict its presence in resection specimens. In contrast, K-ras mutations present in biopsy specimens tended to predict their presence in resections. K-ras mutations were found predominantly in neoplastic mucosae, whereas MSI was found predominantly in regenerative mucosae. The lack of any relationship between MSI and K-ras mutations suggests that MSI in the UC replicative mucosa does not predispose to colonic neoplasia via a K-ras-mediated pathway. This is probably related to the fact that the MSI is generally low-level MSI.

Adolescent↗
PubMed2000

The Vienna classification of gastrointestinal epithelial neoplasia.

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

Adenoma↗
PubMed1999

A germline hMSH2 alteration is unrelated to colonic microsatellite instability in patients with ulcerative colitis.

Recently, a polymorphism in the hMSH2 DNA mismatch repair gene has been associated with the development of dysplasia in ulcerative colitis (UC) patients. This polymorphism is of interest because DNA mismatch repair defects result in alterations in microsatellite stability. The current study was designed to determine whether this hMSH2 polymorphism associates with the development of microsatellite instability and dysplasia in UC patients. The hMSH2 genotype of 96 UC patients was determined by direct DNA sequencing. In addition, we examined 363 samples of colonic mucosa from 93 of these UC patients for microsatellite mutation by polymerase chain reaction (PCR) at eight loci. Three cases had insufficient DNA for microsatellite instability studies. The hMSH2 polymorphism was identified in 13 of the 96 patients examined (13.5%). The polymorphism was observed in 7 of 46 patients with dysplasia (15.2%), and in 6 of 50 patients without dysplasia (12.0%). Microsatellite instability was identified in 35 tissue samples (25 regenerative, one indefinite for dysplasia, eight dysplasias, and one invasive carcinoma) from 26 patients. Two patients with microsatellite instability had the hMSH2 alteration. The 11 remaining patients had the hMSH2 polymorphism, but no evidence of microsatellite mutations with any of the markers tested. We were unable to confirm the previously reported findings that the specific germline hMSH2 alteration represents a marker for increased risk of dysplasia in patients with UC, nor is it responsible for the development of microsatellite instability in these patients.

Carcinoma↗
PubMed1999

Microsatellite instability is absent in liver and biliary mucosa of patients with primary sclerosing cholangitis.

Microsatellite instability occurs in the colonic mucosa of patients with inflammatory bowel disease and may predispose the mucosa to neoplastic transformation. It is unknown whether microsatellite instability also plays a role in the neoplastic risk associated with primary sclerosing cholangitis. We examined 134 tissue samples from 21 patients with sclerosing cholangitis for microsatellite instability at eight loci. All tissues were also stained immunohistochemically using an antibody to the proliferation marker Ki-67. Microsatellite instability did not occur in any samples from the intrahepatic or extrahepatic biliary system, although one patient demonstrated instability in the colon. Ki-67 indices ranged from 0 to 2.5 in nondysplastic biliary epithelium and from 1.5 to 29.4 in areas of dysplasia. The absence of microsatellite instability in sclerosing cholangitis suggests that the genetic basis of neoplastic progression in chronic inflammatory disease of the bile ducts differs from that of intestinal cancers arising in the setting of chronic inflammatory bowel disease and may relate to differences in the microenvironment in these two sites.

Adult↗
PubMed1999

Carboxyl ester lipase activity in milk prevents fat-derived intestinal injury in neonatal mice.

Carboxyl ester lipase (bile salt-stimulated lipase) is a pancreatic enzyme capable of hydrolyzing esters of cholesterol and fat-soluble vitamins. It also efficiently digests triglycerides (TG) into free fatty acids and glycerol and is abundant in the milk of humans and several other species. We used the mouse as a model to test the hypothesis that milk-derived carboxyl ester lipase (CEL) digests milk TG and that without its activity milk lipids and their digestion intermediates can disrupt the intestinal epithelium of neonates. CEL protein and enzymatic activity were shown to be abundant in mouse milk. After 24-h administration of the CEL-specific inhibitor, WAY-121,751-5, the small intestines of treated and control neonates were analyzed histologically for signs of fat malabsorption and injury to their villus epithelium. In vehicle-fed controls, TG were digested and absorbed in the duodenum and jejunum, whereas, in inhibitor-fed littermates, large intracellular neutral lipid droplets accumulated in enterocytes of the ileum, resulting in damage to the villus epithelium. Similar results were observed in neonates nursed by CEL knockout females compared with heterozygous controls. The results suggest that lack of CEL activity causes incomplete digestion of milk fat and lipid accumulation by enterocytes in the ileum of neonatal mice.

Administration, Oral↗
PubMed1999

p53 immunoreactivity and single-strand conformational polymorphism analysis often fail to predict p53 mutational status.

The intent of this study was to investigate the ability of p53 expression and single-strand conformational polymorphism analysis (SSCP) to predict p53 mutational status in archival, paraffin-embedded tissues of gastric cancer. We evaluated paraffin-embedded tissues from 78 patients with advanced gastric cancer. The mutational status of the p53 gene (exons 5-9) was examined by SSCP analysis and by direct sequencing. These results were compared with p53 expression as assessed by immunohistochemical analysis (IHC). We graded p53 expression on a scale from 0 to 8 on the basis of both the intensity and the number of cells staining. Overall, we detected p53 immunoreactivity in 75.6% of the gastric cases; 19 (32.2%) of these cases scored from 1 to 4, and 40 (67.8%) cases scored from 5 to 8. p53 gene mutations were detected in 18 cases (23.1%) by SSCP and in 28 cases (36%) by direct sequencing. Thus, SSCP failed to detect 38% of the mutations found by sequencing. The majority of missed mutations involved exons 7 and 8. The concordance between IHC and SSCP was 37%, and the concordance between IHC and direct sequencing was 50%. Forty-five percent of cases positive by IHC failed to show mutations in exons 5 through 9. Five percent of cases negative by IHC (4 cases) contained mutations. One had a 1-base pair insertion; one had a mutation that resulted in a stop codon; the third had a mutation in exon 8; and the fourth had a mutation in both exons 5 and 8. Our findings indicate that p53 immunoreactivity correlates with the presence or absence of gene mutations in 50% of advanced gastric cancers when exons 5 through 9 are examined and that IHC cannot be reproducibly used as a marker of mutation in the most commonly mutated exons of the p53 gene. Furthermore, the sensitivity of SSCP for detecting mutations is only 62%. Thus, SSCP analysis cannot be used reliably to screen for p53 mutations.

Base Sequence↗
PubMed1998

Multifocal neoplasia involving the colon and appendix in ulcerative colitis: pathological and molecular features.

A patient with ulcerative colitis, extensive dysplasia, multifocal colon cancer, and an appendiceal cystadenoma is described. A 48-year-old man with a 26-year history of ulcerative colitis (UC) had extensive dysplasia involving nearly the entire colon and four dysplasia-associated mass lesions (DALMs). Four invasive adenocarcinomas were present. This case is the first documentation of a DALM (mucinous cystadenoma) arising in the appendix in the setting of UC. The genetic alterations present in the various lesions were analyzed. The molecular profiles of the neoplastic lesions differed. Mutations were found in p53 and ras genes, and one site showed microsatellite instability in a single genetic locus. These molecular abnormalities develop before invasive cancer develops, and may undergo clonal expansion to create large mucosal patches containing certain cells with genetic alterations. The diversity of the early changes suggests that the recurrent inflammation characteristic of long-standing UC randomly damages genes known to participate in colon carcinogenesis and that it affects multiple target genes. The findings also support a multiclonal origin of synchronous tumors because the molecular phenotypes of the preinvasive lesions differed at various sites.

Appendiceal Neoplasms↗
PubMed1998

Adenoma-carcinoid tumors of the colon.

OBJECTIVE: Neoplastic lesions containing both an adenomatous component and a carcinoid component are rare. To our knowledge, only two such lesions have been reported previously in the large intestine. We report two additional cases to further delineate the histologic features of these lesions and discuss their possible origin. DESIGN: Cases from the surgical pathology files, including consultation material, of the University of Cincinnati (Ohio) were reviewed. PATIENTS: One patient refused repeat colonoscopy at 6 months and subsequently was lost to follow-up. The other patient died 26 months after a hemicolectomy without evidence of recurrence. RESULTS: One lesion represents a collision tumor in which the two histologic components lay adjacent to one another without intermingling. The other is a composite tumor in which the components intermingled in such a way that in some areas the two components were difficult to distinguish from one another. CONCLUSIONS: Although both lesions contain dual components, we believe they are fundamentally different and that they arose from different mechanisms. Definite conclusions regarding prognosis cannot be made owing to the rarity of these lesions; however, there is no evidence to suggest they behave aggressively.

Adenoma↗
PubMed1998

Increased cell proliferation characterizes Crohn's disease.

Patients with long-standing Crohn's disease (CD), a chronic inflammatory intestinal disease, are at increased risk for intestinal cancer. The neoplasia likely results, in part, from deregulated cell proliferation, which allows mutations to become fixed in the crypt progenitor cells. We postulated that tissues derived from patients with CD would exhibit increased mucosal proliferation. Therefore, we examined specimens from 27 consecutive patients with chronic CD with a monoclonal antibody directed against the proliferation marker, Ki-67. The tissues were evaluated histologically, and the Ki-67 immunostaining patterns were recorded. The antibody to Ki-67 stained the bases of the crypts in both the small and large intestines. The mean number of Ki-67 immunoreactive cells in the normal crypt was 34.1 versus 95.1 in the regenerative mucosa and O in areas of pyloric metaplasia (P < .00001). Ki-67 staining of the mucosa of patients with CD confirmed that cell proliferation is markedly increased and that the replicating compartment of each crypt during regeneration is expanded. We concluded that the increased cell proliferation might predispose the mucosa to mutational events, thereby increasing the cancer risk in these patients. The lack of proliferation in areas of pyloric metaplasia might represent a mucosal adaptive response of the lower crypt that decreases the number of cycling cells vulnerable to genetic damage. Furthermore, growth factors produced by these cells might promote healing of the damaged mucosa.

Adult↗
PubMed1997

Amplification and expression of the cyclin D1 gene in anal and esophageal squamous cell carcinomas.

Cyclin D1 is a cell-cycle regulator and candidate proto-oncogene implicated in the pathogenesis of numerous tumor types. Amplification of the cyclin D1 gene occurs commonly in esophageal squamous cell carcinomas. However, no studies have examined the role of cyclin D1 in anal carcinogenesis. We examined 20 esophageal squamous cell carcinomas and 24 anal carcinomas for cyclin D1 alterations. Protein expression was evaluated by immunohistochemistry using the cyclin DIGM antibody (Novocastra, Newcastle upon Tyne, UK). Cyclin D1 amplification was examined by fluorescent in situ hybridization (FISH), using a cyclin D1 probe obtained from Toshiya Inaba at St. Jude Children's Research Hospital, Memphis, TN. The FISH sections were analyzed using a Leica (Deerfield, IL) confocal microscope. By immunohistochemistry, 75% of esophageal carcinomas showed evidence of cyclin D1 expression. Cyclin D1 amplification was detected by FISH in 65% of esophageal cancers. There was good correlation between cyclin D1 protein expression and gene amplification, although some tumors showed protein overexpression in the absence of gene amplification. Among the 24 anal carcinomas studied, 8% showed weak cyclin D1 immunoreactivity in rare tumor cells. None of the anal tumors showed cyclin D1 amplification. We conclude that cyclin D1 alterations are common in esophageal carcinomas but do not appear to be important in anal carcinogenesis. Immunohistochemical detection of cyclin D1 protein overexpression is a good predictor of cyclin D1 amplification.

Anus Neoplasms↗
PubMed1997

Regenerative lesions in ulcerative colitis are characterized by microsatellite mutation.

An increased risk of colon cancer has been observed in individuals with long-standing ulcerative colitis (UC). In order to identify molecular genetic markers for the development of neoplasia in UC individuals, we isolated DNA from normal, regenerative, and dysplastic mucosa, as well as from colon carcinomas from UC patients, and evaluated it for the presence of mutations in microsatellite DNA sequences. DNAs isolated from regenerative mucosa displayed microsatellite mutation. These observations suggest that DNA mutation is an early event in the UC disease process.

Colitis, Ulcerative↗
PubMed1997

Aggressiveness of colon carcinoma in blacks and whites. National Cancer Institute Black/White Cancer Survival Study Group.

Black patients with colon cancer in the Black/White Cancer Survival Study were found to have a poorer survival than white patients. More advanced-stage disease at diagnosis was the primary determinant, accounting for 60% of the excess mortality. After adjusting for stage, factors such as poverty, other socioeconomic conditions, and treatment did not further explain the remaining survival deficit. This study examined the aggressiveness of colon tumors in blacks and whites to explore its role in the racial survival differences. Tumor characteristics of 703 cases of newly diagnosed invasive colon adenocarcinoma were centrally evaluated by a gastrointestinal pathologist, blinded in regard to the age, race, and sex of the patients. Blacks were less likely to have poorly differentiated (grade 3) tumors [odds ratio (OR), 0.44; 95% confidence interval, 0.22-0.88] and lymphoid reaction (OR, 0.49; 95% confidence interval, 0.26-0.90) when compared with whites. These black/white (B/W) differences remained statistically significant after adjusting for age, sex, metropolitan area, summary stage, socioeconomic status, body mass index, and health care access and utilization. In addition, blacks were less likely to have high-grade (grade 3) nuclear atypia, mitotic activity, and tubule formation, although these ORs did not reach a statistical significance level of 0.05. Similar B/W differences were observed for patients with advanced disease but not with early stage. Comparison by anatomical subsite showed that blacks had statistically significantly better differentiated tumors for cancers of the proximal and transverse colon but not for the distal. No racial differences were found for blood vessel and lymphatic invasion, necrosis, fibrosis, and mucinous type of histology. The findings, therefore, are the opposite of those hypothesized. After adjusting for stage, more aggressive tumor characteristics do not explain the adverse survival differential in blacks. This suggests that there may be racial differences in environmental exposure, and that the intensity and mode of delivery of carcinogen insult as well as host susceptibility may differ by race and anatomical subsite. Future studies should explore the B/W differences in tumor biology using molecular markers that precede the conventional histological parameters evaluated here.

Adult↗
PubMed1996

The pattern of cell proliferation in neoplastic and nonneoplastic lesions of ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by repeated episodes of inflammation and epithelial regeneration. Patients with long-standing UC have an increased risk for the development of dysplasia and subsequent colon carcinoma. Because dysplasia likely results from deregulatec cell proliferation, the authors examined Ki-67 immunoreactivity in tissues from UC patients to examine patterns of proliferation in neoplastic and nonneoplastic lesions. METHODS: One hundred and eighty-seven specimens were obtained from 41 patients with UC and each lesion evaluated according to the International Classification for Dysplasia in Inflammatory Bowel Disease. All sections were stained with a monoclonal antibody directed against the proliferation marker Ki-67, and evaluated by three observers. RESULTS: Statistically significant differences in the pattern of Ki-67 immunoreactivity were observed between nonneoplastic and neoplastic lesions. In regenerative mucosa, Ki-67 immunoreactivity localized to the bases of the crypts, and the proliferative zone appeared expanded. In dysplasia, Ki-67 staining was prominent in cells in the superficial mucosa, as well as in cells at the crypt bases. In some dysplasias and all invasive carcinomas, Ki-67 staining was diffusely distributed throughout the crypts, suggesting complete deregulation of normal cell proliferation. CONCLUSIONS: Cell proliferation is markedly increased in patients with UC, and appears abnormally regulated in neoplastic lesions. Furthermore, Ki-67 staining helps delineate areas of dysplasia in cases in which the distinction from regenerative mucosa is unclear. The increased cell proliferation that occurs in patients with UC may predispose the mucosa to mutational events, thereby increasing cancer risk in these patients.

Adult↗
PubMed1996

Detection of human papillomavirus in esophageal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV) DNA has been identified in esophageal carcinomas. However, the incidence of HPV varies significantly in different geographic locations. In the current study, neoplasms from two separate geographic regions were analyzed for the presence of HPV DNA: METHODS: One hundred and ten esophageal squamous cell carcinomas, 83 from Beijing, China and 27 from Cincinnati, Ohio, were examined for the presence of HPV DNA: In situ hybridization and polymerase chain reaction (PCR) using both consensus primers for the HPV L1 gene and type specific primers for the E6 gene of HPV types 6, 16, and 18 were performed. RESULTS: In situ hybridization failed to demonstrate any HPV type (6, 11, 16, 18, 31, 33, or 35) in any tumor specimen. Likewise, PCR using consensus primers for the HPV L1 gene was negative in all samples. Three of the Chinese specimens (4.29%) were positive for HPV using E6 type specific primers. One tumor contained HPV type 6 DNA, whereas the other 2 contained HPV type 16 DNA. One Cincinnati tumor (4.35%) was positive for HPV 16 by type specific primer. None of the specimens contained HPV 18 DNA. CONCLUSIONS: The incidence of HPV DNA in esophageal carcinoma specimens from Beijing, China and Cincinnati, Ohio is similar. The incidence of HPV in tumors from Beijing is significantly lower than that reported for those from other regions of China where the incidence of esophageal cancer is higher. Thus, although HPV may play a role in esophageal carcinogenesis, this role may be more pronounced in those regions of the world with a high incidence of the disease, and may be less important in areas with moderate or low risks for esophageal cancer.

Adult↗