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P Chaubert

Publications and source records attributed to P Chaubert.

At least 19 recordsLinked to original sources
PubMed2001

Myocardial angiogenesis induction with bone protein derived growth factors (animal experiment).

Myocardial angiogenesis induction with vascular growth factors constitutes a potential strategy for patients whose coronary artery disease is refractory to conventional treatment. The importance of angiogenesis in bone formation has led to the development of growth factors derived from bovine bone protein. Twelve pigs (mean weight, 73 +/- 3 kg) were chosen for the study. In the first group (n = 6, growth factor group) five 100 micrograms boluses of growth factors derived from bovine bone protein, diluted in Povidone 5%, were injected in the lateral wall of the left ventricle. In the second group (n = 6, control group), the same operation was performed but only the diluting agent was injected. All the animals were sacrificed after 28 days and the vascular density of the left lateral wall (expressed as the number of vascular structures per mm2) as well as the area of blood vessel profiles per myocardial area analysed were determined histologically with a computerised system. The growth factor group had a capillary density which was significantly higher than that of the control group: 12.6 +/- 0.9/mm2 vs 4.8 +/- 0.5/mm2 (p < 0.01). The same holds true for the arteriolar density: 1 +/- 0.2/mm2 vs 0.3 +/- 0.1/mm2 (p < 0.01). The surface ratios of blood vessel profiles per myocardial area were 4900 +/- 800 micron 2/mm2 and 1550 +/- 400 micron 2/mm2 (p < 0.01) respectively. In this experimental model, bovine bone protein derived growth factors induce a significant neovascularisation in healthy myocardium, and appear therefore as promising candidates for therapeutic angiogenesis.

Animals↗
PubMed2001

A novel highly informative polyA microsatellite on the telomeric side of the INK4a/ARF locus.

The INK4a/ARF locus encodes two cell cycle-regulatory proteins, p16(INK4a)and p14(ARF). Inactivation of the p16(INK4a)(MTS1) tumor suppressor gene by mutations, promoter methylation or gene deletions is a common event in the development of many different human tumors. The present report describes a novel polyA mononucleotide repeat situated 7.2 kb on the telomeric side of the INK4a/ARF locus. This highly polymorphic microsatellite marker (heterozygote frequency: 0.78) proved to be efficient for p16 allele loss and microsatellite instability analyses in human colon cancer.

Adenocarcinoma↗
PubMed2001

Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location.

PURPOSE: The aim of this study was to determine whether tumor location proximal or distal to the splenic flexure is associated with distinct molecular patterns and can predict clinical outcome in a homogeneous group of patients with Dukes B (T3-T4, N0, M0) colorectal cancer. It has been hypothesized that proximal and distal colorectal cancer may arise through different pathogenetic mechanisms. Although p53 and Ki-ras gene mutations occur frequently in distal tumors, another form of genomic instability associated with defective DNA mismatch repair has been predominantly identified in the proximal colon. To date, however, the clinical usefulness of these molecular characteristics remains unproven. METHODS: A total of 126 patients with a lymph node-negative sporadic colon or rectum adenocarcinoma were prospectively assessed with the endpoint of death by cancer. No patient received either radiotherapy or chemotherapy. p53 protein was studied by immunohistochemistry using DO-7 monoclonal antibody, and p53 and Ki-ras gene mutations were detected by single strand conformation polymorphism assay. RESULTS: During a mean follow-up of 67 months, the overall five-year survival was 70 percent. Nuclear p53 staining was found in 57 tumors (47 percent), and was more frequent in distal than in proximal tumors (55 vs. 21 percent; chi-squared test, P < 0.001). For the whole group, p53 protein expression correlated with poor survival in univariate and multivariate analysis (log-rank test, P = 0.01; hazard ratio = 2.16; 95 percent confidence interval = 1.12-4.11, P = 0.02). Distal colon tumors and rectal tumors exhibited similar molecular patterns and showed no difference in clinical outcome. In comparison with distal colorectal cancer, proximal tumors were found to be statistically significantly different on the following factors: mucinous content (P = 0.008), degree of histologic differentiation (P = 0.012), p53 protein expression, and gene mutation (P = 0.001 and 0.01 respectively). Finally, patients with proximal tumors had a marginally better survival than those with distal colon or rectal cancers (log-rank test, P = 0.045). CONCLUSION: In this series of Dukes B colorectal cancers, p53 protein expression was an independent factor for survival, which also correlated with tumor location. Eighty-six percent of p53-positive tumors were located in the distal colon and rectum. Distal colon and rectum tumors had similar molecular and clinical characteristics. In contrast, proximal neoplasms seem to represent a distinct entity, with specific histopathologic characteristics, molecular patterns, and clinical outcome. Location of the neoplasm in reference to the splenic flexure should be considered before group stratification in future trials of adjuvant chemotherapy in patients with Dukes B tumors.

Adenocarcinoma↗
PubMed2001

Is the GraftConnector a valid alternative to running suture in end-to-side coronary arteries anastomoses?

BACKGROUND: An animal study was carried out to compare long-term patency rates of coronary anastomoses performed with the GraftConnector versus running suture technique. METHODS: 10 sheep, 45 to 55 kg, underwent off-pump coronary artery bypass grafting (right internal mammary artery to left anterior descending artery). In 5 animals, the anastomosis was performed with a GraftConnector and in 5 animals with 7-0 running suture. Intraoperative fluoroscopy and a fluoroscopic control at 6 months were performed. After 6 months, the animals were sacrificed and the anastomoses were examined histologically. RESULTS: All animals survived at 6 months with 100% anastomosis patency rates in both groups. In the GraftConnector group, the anastomosis diameter at 6 months fluoroscopy was 118% of native left anterior descending artery versus 97% of the control group. Luminal anastomotic width at histology was 1.7 +/- 0.2 mm in the device group versus 1.6 +/- 0.1 mm in the control group. Mean intimal hyperplasia thickness was 0.21 +/- 0.1 mm in the device group versus 0.01 mm in the control group. CONCLUSIONS: The GraftConnector provides a consistent and reproducible coronary artery anastomosis and reduces technical demand and manual dexterity in coronary operations. Long-term results demonstrate that off-pump coronary artery bypass grafting performed with the GraftConnector had the same patency rate and luminal width as those performed with running suture.

Anastomosis, Surgical↗
PubMed2001

Intrachannel versus interchannel application of angiogenic factors in transmyocardial laser revascularization.

BACKGROUND AND OBJECTIVE: Theoretically myocardial angiogenesis of laser injury can be further enhanced by the addition of angiogenic growth factors. The influence of the way of administration of these factors on vascular growth around the channels is still unclear. MATERIALS AND METHODS: 18 pigs (mean weight 72 +/- 5.2 kg) were randomized to either triads of transmyocardial laser revascularization (TMLR) channels (group 1, n = 6) or isolated channels (group 2, n = 6), or a control group (n = 6). The animals had injections of bovine bone derived growth factor mixture either in the center of the triads in group 1 or within the channels themselves in group 2. Animals were sacrificed one month later for histological analysis. RESULTS: The vascular densities of myocardial areas within the triads of group 1 and around the channels in group 2 were significantly larger than in the control group: 15.2 +/- 3.7/mm2 and 14.2 +/- 3.5/mm2 respectively vs 5.3 +/- 1.6/mm2 (p < 0.001 for both differences). Differences of densities between group 1 and 2 were not statistically significant (p = 0.6). CONCLUSIONS: In this porcine model, the addition of a bovine bone derived growth factor mixture to TMLR significantly stimulates angiogenesis in the areas adjacent to the channels. The place of injection does not influence the angiogenesis intensity.

Angiogenesis Inducing Agents↗
PubMed2001

Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer.

The INK4a-ARF locus encodes two tumor suppressor proteins involved in cell-cycle regulation, p16INK4a and p14ARF, whose functions are inactivated in many human cancers. The aim of this study was to evaluate p14ARF and p16INK4a gene inactivation and its association with some clinocopathological parameters in colon cancer. The mutational and methylation status of the p14ARF and p16INK4a genes was analyzed in 60 primary colon carcinomas and 8 colon cancer cell lines. We have identified the first two reported mutations affecting exon 1beta of p14ARF in the HCT116 cell line and in one of the primary colon carcinomas. Both mutations occur within the N-terminal region of p14ARF, documented as important for nucleolar localization and interaction with Mdm2. Tumor-specific methylation of the p14ARF and p16INK4a genes was found in 33% and 32% of primary colon carcinomas, respectively. Methylation of the p14ARF was inversely correlated with p53 overexpression (p = 0.02). p14ARF and p16INK4a gene methylation was significantly more frequent in right-sided than in left-sided tumors (p = 0.02). Methylation of the p14ARF gene occurred more frequently in well-differentiated adenocarcinomas (p = 0.005), whereas the p16INK4a gene was more often methylated in poorly differentiated adenocarcinomas (p = 0.002). The present results underline the role of p14ARF and p16INK4a gene inactivation in the development of colon carcinoma. They suggest that the methylation profile of specific genes, in particular p14ARF and p16INK4a, might be related to biologically distinct subsets of colon carcinomas and possibly to different tumorigenic pathways.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Primary neuroendocrine carcinoma of the liver: an autopsy case.

An autopsy case of primary hepatic neuroendocrine carcinoma is described. A 72-year-old man had a large tumor mass measuring 22 cm in its greatest diameter and localized to the right, left and caudal lobes of the non-cirrhotic liver. Microscopically, the tumor was composed of middle-sized pleomorphic cells organized in ribbons or trabeculae, with scanty intersecting fibrous septae. Immunohistochemically, the tumor cells were positive for multikeratin C11, chromogranin A and synaptophysin. The patient also had metastases in the bone marrow. No alternative primary source of endocrine tumor was detected. The patient died 4 days after presentation.

Aged↗
PubMed2001

Expression of CD44 and its isoforms in the fetal neuroblasts.

CD44 is a polymorphic transmembrane glycoprotein that exists as multiple isoforms resulting from alternative splicing and posttranslational modifications. Enhanced expression of CD44 has been correlated to the tumorigenicity and metastatic behavior in different malignant tumors. In contrast, human neuroblastomas exhibit an inverse correlation between CD44 expression and tumor malignancy. To determine whether there is a CD44 silencing in sympatho-adrenal precursors as a possible explanation for the down-regulation of CD44 in neuroblastomas, the expression of standard CD44H and v6, v7, v7v8, or v10 isoforms was analyzed by immunohistochemistry in human adrenal glands of 14- to 20-week-old gestational age fetuses. All of the fetal neuroblasts localized in the adrenal gland parenchyma and migrating from the sympathetic nerve chain into the fetal adrenal cortex strongly expressed CD44H but none of the CD44 isoforms could be detected in these cells. In contrast, a strong expression of CD44v7 and v6 was detected in the fetal adrenal cells. These results indicate that, as for many other cell types, the CD44H expressed by fetal neuroblasts may contribute to controlling their migration into the adrenal medulla and that the down-regulation of CD44H in neuroblastoma cells should be explained by mechanisms other than the fetal suppression of CD44H expression in their normal counterparts.

Adrenal Glands↗
PubMed2001

Does laser injury induce a different neovascularisation pattern from mechanical or ischaemic injuries?

AIM: To analyse the arteriolar pattern of laser induced channels and their surroundings compared with mechanical and ischaemic injury. METHODS: 24 pigs were randomised to a myocardial infarction group, a transmyocardial laser revascularisation group, a needle group, or a control group. In the laser revascularisation and needle groups, five channels were created either with a 1.75 mm probe holmium-YAG laser or a Tru-cut needle of the same size. Animals were killed 28 days later. Morphometric analysis of vascular density was expressed as the mean (SD) number of arteriolar structures/cm(2). RESULTS: Laser and needle channels were completely invaded by granulation tissue. Their surface areas did not differ significantly: 2.28 (0.7) mm(2) and 2.38 (1.1) mm(2), respectively (p = 0.82). Within both types of channel, arteriolar density was significantly increased in comparison with the myocardial infarction scar: 197 (52)/cm(2) and 190 (64)/cm(2), respectively (p = 0.8) versus 56 (20)/cm(2) (p < 0.001 for both comparisons). The area of 1 mm width immediately adjacent to the laser and needle channels showed a density of 25 (16)/cm(2) and 23 (18)/cm(2), respectively, which is similar to that of normal tissue (28 (10)/cm(2); p = 0.6 and p = 0.4, respectively). The mean arteriolar diameter was similar throughout all the regions analysed. CONCLUSIONS: Both laser and needle channels produce a similar increase in arteriolar structures, which is limited to the lesion itself. This suggests that laser injury is not more potent as an angiogenic stimulator than mechanical injury, which in turn is superior to infarction.

Animals↗
PubMed2000

Tumor cell budding and laminin-5 expression in colorectal carcinoma can be modulated by the tissue micro-environment.

Expression of laminin-5 alpha3, beta3 and gamma2 protein subunits was investigated in colorectal adenocarcinomas using immunostaining and confocal microscopy. The laminin-5 heterotrimer was found in basement membranes and as extracellular deposits in tumor stroma. In contrast to the alpha3 subunit, which was under-expressed, the gamma2 and beta3 subunits were detected in the cytoplasm of carcinoma cells dissociating (budding) from neoplastic tubules, suggestive of focal alterations in laminin-5 assembly and secretion. Laminin-5 gamma2 or beta3 subunit-reactive budding carcinoma cells expressed cytokeratins but not vimentin; they did not proliferate and were not apoptotic. Furthermore, expression of laminin-5 gamma2 and beta3 subunits in budding cells was associated with focal under-expression of the E-cadherin-beta-catenin complex. Results from xenograft experiments showed that budding activity in colorectal adenocarcinomas could be suppressed when these tumors grew at ectopic s.c. sites in nude mice. In vitro, cultured colon carcinoma cells, but not adenoma-derived tumor cells, shared the laminin-5 phenotype expressed by carcinoma cells in vivo. Using colon carcinoma cell lines implanted orthotopically and invading the cecum of nude mice, the laminin-5-associated budding was restored, indicating that this phenotype is not only determined by tumor cell properties but also dependent on the tissue micro-environment. Our results indicate that both laminin-5 alpha3 subunit expression and cell-cell cohesiveness are altered in budding carcinoma cells, which we consider to be actively invading. We propose that the local tissue micro-environment contributes to these events.

Adenocarcinoma↗
PubMed2000

Physical map of 17p13 and the genes adjacent to p53.

Genetic lesions in the p53 tumor suppressor gene are the most frequently observed alterations in human cancers. Typically in tumors, one allele of the p53 gene is initially mutated, followed by deletion of the remaining wildtype allele. In human colon cancer, for example, approximately 70% of late stage tumors are hemizygous mutant p53. Since the precise gene environment surrounding the p53 gene is not known, the neighboring genes concomitantly lost with wildtype p53 deletion remain undetermined. A restriction enzyme map and clone array of 1.1 Mb surrounding the p53 gene were constructed using a combination of YAC, BAC, NotI linking, and NotI jumping clones. The resulting physical map and clone array include approximately 400 kb telomeric and 700 kb centromeric to the p53 gene. Sequence determination and analysis adjacent to NotI and AscI sites, indicative of CpG islands, allowed the rapid identification of numerous genes within the cloned region. Twenty-seven transcription units were identified, including 18 characterized genes. Limited analysis of primary human colon tumors, hemizygous for the p53 gene, indicates loss of the entire 1.1-Mb region upon deletion of wildtype p53.

Chromosomes, Artificial, Yeast↗
PubMed2000

p53 and Ki-ras as prognostic factors for Dukes' stage B colorectal cancer.

Mutations of the TP53 and Ki-ras genes have been reported to be of prognostic importance in colorectal carcinomas. An increased intracellular concentration of the p53 protein, although not identical to, is sometimes seen in tumours with TP53 mutation and has been correlated with poor prognosis in some tumour types. Previous colorectal cancer studies, addressing the prognostic importance of Ki-ras mutation and TP53 aberrations, yielded contradictory results. The aim of this study was to determine in a clinically and therapeutically homogeneous group of 122 sporadic Dukes' B colorectal carcinomas with a median follow-up of 67 months (3-144 months) whether or not p53 protein expression, TP53 mutation and K-ras mutation correlated with prognosis. p53 staining was performed by immunohistochemistry, using the monoclonal antibody DO7 on paraffin-embedded tissue. Mutations in exons 5-8 of the TP53 gene and in codons 12 and 13 of the K-ras gene were assayed in paraffin-embedded tissue by the single-strand conformation polymorphism (SSCP) assay. Nuclear p53 staining was found in 57 (47%) tumours. Aberrant migration patterns indicating mutation of the TP53 gene were found in 39 (32%) tumours. Forty-six carcinomas (38%) showed a mutation of the Ki-ras codons 12 or 13. In a univariate analysis, patients with wild-type TP53 status showed a trend towards better survival, compared with those with mutated TP53 (log-rank test, P = 0.051). Likewise, tumours immunohistochemically positive for p53 showed a worse prognosis than p53-negative tumours (P = 0.010). The presence or absence of mutations in Ki-ras did not correlate with prognosis (P = 0.703). In multivariate analysis, only p53 immunoreactivity emerged as an independent marker for prognosis hazard ratio (HR) = 2.16, 95% confidence interval (CI) 1.12-4.11, P = 0.02). Assessment of p53 protein expression is more discriminative than TP53 mutation to predict the outcome of Dukes' stage B tumours and could be a useful tool to identify patients who might benefit from adjuvant therapy.

Adenocarcinoma↗
PubMed2000

Improved neoangiogenesis in transmyocardial laser revascularization combined with angiogenic adjunct in a pig model.

Recent research has revealed neoangiogenesis as a basic phenomenon in transmyocardial laser revascularization (TMLR). Theoretically, myocardial neoangiogenesis could be further enhanced by the addition of angiogenic growth factors. Triads of TMLR channels were created in the lateral wall of the left ventricles of 12 pigs (mean body weight 73+/-5 kg), using a holmium:yttrium-aluminium garnet (YAG) laser. The animals were allocated randomly either to receive an injection of 100 microg of a bovine bone-derived growth factor mixture within the triads (n=6), or to a control group (n=6). Animals were killed 1 month later. Capillary and arteriolar densities were determined by computed morphometric analysis of histological sections of the triads. The capillary density of myocardial areas within the triads was significantly greater in the group receiving the bovine bone-derived growth factor mixture than in the control group (14.3+/-3.5/mm(2) and 5.7+/-1.4/mm(2) respectively; P<0.001). The difference was also significant when considering arteriolar density (0.7+/-0.4/mm(2) and 0.2+/-0.1/mm(2) respectively; P<0.001). For comparison, capillary and arteriolar densities of the TMLR channel scars were 48.7+/-9.7 and 1.9+/-0. 5/mm(2) respectively in the angiogenic group, and 46.3+/-13.7 and 2. 3+/-1.3/mm(2) respectively in the control group (no significant differences). These results demonstrate that the addition of angiogenic factors to TMLR stimulates neoangiogenesis significantly in the areas adjacent to the channels, but not within the channel scars. The latter are themselves strongly vascularized. Hence this combined approach, potentiating the effect of TMLR by establishing vascular connections between the neovessels of the channel scars, has the potential for improved clinical outcome.

Animals↗
PubMed1999

[Mechanism of action of transmyocardial laser revascularization (animal experiment)].

Transmyocardial laser revascularisation (TMLR) has emerged as an efficient treatment for angina refractory to conventional therapies. Moreover, some studies have suggested improvement of cardiac function. Its mechanism of action, initially attributed to blood flow from the ventricular cavity through the channels toward the ischaemic myocardium, remains to be defined. 21 pigs were randomised to TMLR of the left lateral wall (TMLR group; n = 7), to myocardial infarction (MI group; n = 7), or to both (TMLR-MI group; n = 7). In each group one animal was sacrificed at postoperative day 0, 7, 14 and 21, and 3 animals at postoperative day 28. The lateral wall of the left ventricle was fixed in 4% formaldehyde and sliced in a plane perpendicular to the channels for histological analysis. The evolution of the cross-section area of the lesions as well as their vascular densities at postoperative day 28, expressed as number vascular structures per mm2, were studied. All the channels were occluded by a clot at postoperative day 0 and by scar tissue at postoperative day 28. The cross-section area of the lesions diminished from 8.1 +/- 1.3 mm2 at postoperative day 0 to 2.4 +/- 0.2 mm2 at postoperative day 28. At postoperative day 28, the vascular density of scar tissue of the channels in the TMLR group was significantly increased in comparison with that of myocardial infarction in the MI group (47.1 +/- 10.2 vs. 23.8 +/- 9.1; p < 0.01). In the TMLR-MI group, channels scar became indistinguishable from surrounding myocardial infarction scar. In this model, laser channels are occluded early and do not salvage acute ischaemic myocardium. Mechanisms which could explain clinical improvement, as suggested by the results, are intense laser-induced neovascularisation and channel scar retraction (Laplace's law).

Animals↗
PubMed1999

Frequent methylation silencing of p15(INK4b) (MTS2) and p16(INK4a) (MTS1) in B-cell and T-cell lymphomas.

The methylation status of p15(INK4b) (MTS2), p16(INK4a) (MTS1) and p14(ARF) (p16beta) was analyzed in 56 lymphomas by restriction-enzyme related polymerase chain reaction (PCR) (REP), methylation-specific PCR (MSP), and bisulfite genomic sequencing (BGS). Methylation of the p15 and p16 genes was detected, respectively, in 64% and 32% of the B-cell lymphomas, in 44% and 22% of the T-cell lymphomas, and in none of the 5 reactive lymph nodes analyzed. Both p15 and p16 genes were methylated more often in the high-grade (78% and 50%, respectively) than in the low-grade B-cell lymphomas (55% and 21%, respectively). For 5 cases, mapping of the methylated CpGs of the p16 promoter region confirmed the results of REP and MSP. In addition, a large variation in the methylation patterns of p16 exon 1 was observed, not only from one lymphoma to another, but also within a given tumor. Methylation of p15 and p16 was associated with an absence of gene expression, as assessed by reverse transcription-PCR. The p14 gene was unmethylated and normally expressed in all 56 tumors. We found no mutations of p15, p16, or p14 in any of the 56 lymphomas. Our results suggest a role for p15 and p16 gene methylation during lymphomagenesis and a possible association between p15 and p16 inactivation and aggressive transformation in B-cell and T-cell lymphomas.

Carrier Proteins↗
PubMed1999

Are there vascular density gradients along myocardial laser channels?

BACKGROUND: Clinical studies suggest that transmyocardial laser revascularization may improve regional blood flow of the subendocardial layer. The vascular growth pattern of laser channels was analyzed. METHODS: Twenty pigs were randomized to undergo ligation of left marginal arteries (n = 5), to undergo transmyocardial laser revascularization of the left lateral wall (n = 5), to undergo both procedures (n = 5) or to a control group (n = 5). All the animals were sacrificed after 1 month. Computed morphometric analysis of vascular density of the involved area was expressed as number of vascular structures per square millimeter (+/-1 standard deviation). RESULTS: The vascular density of the scar tissue of the laser channel was significantly increased in comparison with myocardial infarction alone: 49.6+/-12.8/mm2 versus 25.5+/-8.6/mm2 (p < 0.0001). The vascular densities of subendocardial and subepicardial channel areas were similar: 52.9+/-16.8/mm2 versus 46.3+/-13.6/mm2 (p = 0.41). The area immediately adjacent to the channels showed a vascular density similar to that of normal tissue: 6.02+/-1.7/mm2 versus 5.2+/-1.9/mm2 (p = 0.08). In the infarction + transmyocardial laser revascularization group, the channels were indistinguishable from infarction scar. CONCLUSIONS: Scars of transmyocardial laser revascularization channels exhibit an increased vascular density in comparison with scar tissue of myocardial infarction, which does not extend into their immediate vicinity. There was no vascular density gradient along the longitudinal axis of the channels.

Animals↗
PubMed1999

Aberrant crypt foci in patients with neoplastic and nonneoplastic colonic disease.

Aberrant crypt foci (ACF) are putative preneoplastic lesions that might represent the earliest morphological lesion visible in colonic carcinogenesis. However, findings concerning the growth and morphological features of these lesions in human studies suggest that ACF are highly heterogeneous in nature. In this study, we evaluated the morphological features of a large number of ACF in colon mucosa of 26 patients with colorectal carcinoma (CRC), four patients with adenoma as well as seven patients with nonneoplastic colonic diseases. By dissecting microscope, 508 ACF were identified, and of these, 378 were sampled for histological examination. The median ACF density (number of ACF/cm2) was significantly higher in the left colon than in the right colon (0.047 v 0.014 ACF/cm2). Unexpectedly, in our series, the overall ACF density was higher in the nonneoplastic colonic diseases than in CRC (0.13 v 0.032 ACF/cm2, P=.0087), cases of nonneoplastic diseases, however, being limited to 7 patients. ACF were significantly larger in colons with CRC or adenoma than in colons with nonneoplastic disease (P < .03). On histological examination, we observed 133 ACF with normal epithelium, 189 ACF with hyperplasia, 27 ACF with atypical hyperplasia, and 29 ACF with dysplasia. We noted a progressive increase of median ACF size from normal mucosa to hyperplasia, atypical hyperplasia, and dysplasia. Dysplastic ACF were more frequently observed in patients with CRC or adenoma and showed predominantly elongated crypt orifices (P < .0001). We conclude that ACF are histologically heterogeneous, encompass a spectrum of lesions of which only a subset are associated with dysplasia and then represent an early step in colorectal carcinogenesis. ACF with dysplasia are characterized by larger size, elongated crypt orifices, and an association with CRC.

Adenocarcinoma↗