Polypoid Adenomas Research Articles

Distinct Chromosomal Imbalances in Nonpolypoid and Polypoid Colorectal Adenomas Indicate Different Genetic Pathways in the Development of Colorectal Neoplasms

Cytogenetic changes are widely unknown for nonpolypoid (synonymously termed as "flat" or "depressed") colorectal adenomas. A comparison with polypoid adenomas will contribute to the discussion whether different genetic pathways for colorectal tumorigenesis depending on its origin from nonpolypoid or polypoid adenomas exist. Tissue samples of nonpolypoid (n = 22), polypoid (n = 28) adenomas, carcinomas ex-nonpolypoid adenomas (n = 9), carcinomas ex-polypoid adenomas (n = 14), and normal colonic mucosa (n = 9) were investigated by comparative genomic hybridization of whole genomic DNA. Chromosomal imbalances were detected from average comparative genomic hybridization profiles for each entity. Nonpolypoid adenomas show recurrent chromosomal losses on chromosomes 16, 17p, 18, 20, and 22 and gains on chromosomes 2q, 4q, 5, 6, 8q, 12q, and 13q. In polypoid adenomas losses of whole chromosomes 16, 18, and 22 and gains of chromosomes 7q and 13 were detected. The frequency of copy number changes was higher in nonpolypoid compared to polypoid adenomas and early onset of chromosomal changes became apparent in low-grade dysplasias of nonpolypoid adenomas. Gains on chromosomes 2q, 5, 6, 8q, and 12q and losses on chromosomes 17p and 20 occurred exclusively in nonpolypoid adenomas, whereas 16p deletions are significantly more frequent in nonpolypoid than in polypoid adenomas. Carcinomas ex-nonpolypoid adenomas are characterized by more complex aberration patterns compared to nonpolypoid adenomas exhibiting frequent losses on chromosomes 8p, 12q, 14, 15q, 16, 17p, 18, and 22 and gains on 3q, 5, 6, 7, 8q, 12q, and 13, respectively. Normal colonic mucosa showed no chromosomal imbalances. Distinct differences of chromosomal imbalances between nonpolypoid and polypoid colorectal adenomas have been characterized that support the hypothesis that different genetic pathways may exist in the development of colorectal adenomas exhibiting nonpolypoid and polypoid phenotype.

Does early polypoid colorectal cancer with depression have a pathway other than adenoma-carcinoma sequence?

In the carcinogenesis of colorectal cancer, the concept of adenoma-carcinoma sequence is widely accepted. In this pathway, polypoid adenoma develops into early polypoid cancer and then progresses to advanced cancer. Alternatively, some groups insist that in the de novo pathway in which early cancers develop without preexisting adenoma, flat or depressed early cancers develop into advanced cancer. According to these two different concepts of carcinogenesis, early polypoid cancers may include two distinct types of lesions, early polypoid cancers without central depression via the adenoma-carcinoma sequence and early polypoid cancers with central depression via de novo carcinogenesis. We analyzed 45 submucosal cancer specimens histologically diagnosed as polypoid by clinicopathological features and K-ras mutation in early polypoid cancers with and without depression to clarify whether there was a difference between the two groups. No significant difference in clinicopathological features was found between the two groups. Also, a high incidence of K-ras mutation was observed in both groups. This suggests that early polypoid cancers with depression have a similar genetic background to polypoid cancers without depression, which follows the adenoma-carcinoma sequence. It is possible that whether or not the tumor has a depression does not indicate the distinct pathway of colorectal carcinogenesis.

The zinc finger protein OZF (ZNF146) is overexpressed in colorectal cancer.

Overexpression of the OZF gene has previously been demonstrated in the majority of pancreatic cancers. However, because the stages of tumour progression in this disease are poorly defined, no conclusion could be drawn concerning the relationship between OZF overexpression and the course of tumour progression. In contrast, initiation and progression steps are well defined in colorectal cancer. Most colon cancers are believed to arise from polypoid adenomas as a result of the gradual accumulation of genetic alterations, allowing the study of genetic events in the early stages of neoplasia. Accordingly, we wanted to assess the frequency of OZF overexpression in this tumour type and the relationship between overexpression and disease stage. Twenty-five colon carcinoma specimens from different sites and at various stages were analysed by immunoblotting using a highly specific mouse monoclonal antibody. Each sample was compared with adjacent normal colonic mucosa. Complementary immunohistochemical analysis was also carried out on a commercially available tissue array to identify cells expressing OZF. Of the 25 tumours analysed by immunoblotting, 20 expressed higher levels of OZF protein than their adjacent normal mucosa. Immunohistochemistry revealed OZF expression in tumour cells of 56/59 carcinomas and occasionally in infiltrating lymphocytes but at lower levels. Little or no staining was observed in cells taken from normal or inflammatory colon specimens. In both immunoblot and immunohistochemistry experiments, no correlation was found between OZF expression and clinical parameters such as TNM classification, stage, localization and age. Immunostaining was observed in low-grade adenomas, indicating that OZF expression occurs very early in the course of tumour progression. OZF expression, infrequent or absent in normal colonic mucosa, is present in more than 80% of colorectal cancers. Dysregulation of the OZF gene is an early event that may be implicated in the genesis of colonic carcinoma and may therefore provide a potential therapeutic target.

Hemorragia digestiva tras tratamiento endoscópico de hamartoma polipoide (adenoma de glándulas de Brunner)

The incidence of polypoidal tumors in the duodenum is scarce and Brunner's gland tumors represent 11% of these proliferations. Brunner's gland polypoid hamartoma or adenoma is a highly infrequent benign polypoid proliferation of Brunner's glands that is usually asymptomatic, although gastrointestinal bleeding or intestinal obstruction may sometimes occur. We present the case of a woman with an incidental diagnosis of duodenal polypoid hamartoma. The lesion was resected with polypectomy loop and at 48 h, the patient presented gastrointestinal bleeding as a complication. We describe the endoscopic treatment of the lesion and this complication.

Molecular analysis of diminutive, flat, depressed colorectal lesions: Are they precursors of polypoid adenoma or early stage carcinoma?

Background: The diminutive, flat depressed colorectal lesion is a possible precursor of early stage carcinoma. However, the significance of this lesion in colon carcinogenesis remains unclear. Methods: Eighty-one diminutive flat lesions (<5 mm diameter) with a central depression (DPdep) were resected colonoscopically and their molecular characteristics were investigated. In parallel, 68 diminutive polyps (<5 mm diameter) with a polypoid growth pattern but no depression (DPpo) were analyzed as controls. After histopathologic diagnosis, only neoplastic tissues were stained by immunohistochemistry for p53 gene and cyclooxygenase 2 (COX-2) and the proliferation marker, Ki-67. Mutation of the K- ras gene was analyzed with the polymerase chain reaction-restriction fragment length polymorphism method by using DNA from microdissected tissue in paraffin sections. Results: Seventy-nine of 81 DPdep and 35 of 68 DPpo were diagnosed as neoplastic. Mild, moderate, and severe dysplasia were found in, respectively, 56, 15, and 8 DPdep polyps, and in 34, 1, and 0 DPpo polyps. Thus, DPdep were more likely to be neoplastic and to exhibit moderate and severe dysplasia compared with DPpo ( p < 0.0001). No DPdep or DPpo was positive for the p53 protein. The proportion of specimens with K- ras codon 12 mutation was 13.4% in diminutive polyps (DP), and tended to be lower in DPdep (8.6%) than in DPpo (25.0%) ( p = 0.073). The median (interquartile range) of the Ki-67 index of DPdep tended to be lower than that of DPpo (respectively, 0.0 [0.0-5.9] vs. 4.5 [0.0-17.1]; p = 0.0281). COX-2 overexpression was observed in 12 of 77 (15.6%) DP and there was no significant difference between DPdep (3 of 23, 13.0%) and DPpo (9 of 54, 16.7%). Conclusion: Diminutive, flat, depressed lesions in this study had low rates of the genetic alterations associated with malignant progression. This indicates that either a different neoplastic mechanism is operative or that these lesions have a lower malignant potential than indicated by their histopathologic features. (Gastrointest Endosc 2002;56:663-71.)

Molecular analysis of diminutive, flat, depressed colorectal lesions: are they precursors of polypoid adenoma or early stage carcinoma?

The diminutive, flat depressed colorectal lesion is a possible precursor of early stage carcinoma. However, the significance of this lesion in colon carcinogenesis remains unclear. Eighty-one diminutive flat lesions (<5 mm diameter) with a central depression (DPdep) were resected colonoscopically and their molecular characteristics were investigated. In parallel, 68 diminutive polyps (<5 mm diameter) with a polypoid growth pattern but no depression (DPpo) were analyzed as controls. After histopathologic diagnosis, only neoplastic tissues were stained by immunohistochemistry for p53 gene and cyclooxygenase 2 (COX-2) and the proliferation marker, Ki-67. Mutation of the K-ras gene was analyzed with the polymerase chain reaction-restriction fragment length polymorphism method by using DNA from microdissected tissue in paraffin sections. Seventy-nine of 81 DPdep and 35 of 68 DPpo were diagnosed as neoplastic. Mild, moderate, and severe dysplasia were found in, respectively, 56, 15, and 8 DPdep polyps, and in 34, 1, and 0 DPpo polyps. Thus, DPdep were more likely to be neoplastic and to exhibit moderate and severe dysplasia compared with DPpo (p < 0.0001). No DPdep or DPpo was positive for the p53 protein. The proportion of specimens with K-ras codon 12 mutation was 13.4% in diminutive polyps (DP), and tended to be lower in DPdep (8.6%) than in DPpo (25.0%) (p = 0.073). The median (interquartile range) of the Ki-67 index of DPdep tended to be lower than that of DPpo (respectively, 0.0 [0.0-5.9] vs. 4.5 [0.0-17.1]; p = 0.0281). COX-2 overexpression was observed in 12 of 77 (15.6%) DP and there was no significant difference between DPdep (3 of 23, 13.0%) and DPpo (9 of 54, 16.7%). Diminutive, flat, depressed lesions in this study had low rates of the genetic alterations associated with malignant progression. This indicates that either a different neoplastic mechanism is operative or that these lesions have a lower malignant potential than indicated by their histopathologic features.

Inverse Relationship between APC Gene Mutation in Gastric Adenomas and Development of Adenocarcinoma

Gastric cancer is common among the world, but genetic mechanisms of gastric carcinogenesis are not well understood. Gastric polypoid adenomas and flat dysplasias are regarded as precursor lesions. However, a detailed molecular study of these lesions has not been done to determine their role as precancerous lesions. We investigated mutations of the APC, beta-catenin, and K-ras genes, and microsatellite instability (MSI) status in 35 adenomas and 47 flat dysplasias without adenocarcinoma, 35 adenomas/dysplasias associated with adenocarcinomas, and 39 adenocarcinomas (20 diffuse type and 19 intestinal type). Somatic APC gene mutations were identified in 76% (59 of 78) of adenomas or flat dysplasias without associated adenocarcinoma, but in only 3% (1 of 30) of adenomas/dysplasias associated with adenocarcinoma, and in only 4% (3 of 69) of adenocarcinomas (P < 0.000001). No mutations of beta-catenin were found in adenocarcinomas, or adenomas/dysplasia without APC mutation. K-ras mutations were detected in 5% (4 of 82) of gastric adenomas/dysplasia without carcinoma, 3% (1 of 39) of adenocarcinomas without associated adenoma/dysplasia, and not in 32 adenocarcinomas with associated adenoma/dysplasia. High level of MSI (MSI-H) was more frequent in gastric adenoma/dysplasia associated with carcinoma (17%, 6 of 35) than in adenomas/dysplasia without carcinoma (3%, 2 of 75; P = 0.01). MSI-H was also more frequent in intestinal type adenocarcinoma (20%, 11 of 54) than in diffuse type (0%, 0 of 20; P = 0.03). APC gene mutations were present in six of nine (67%) of gastric adenomas/dysplasias with low level of MSI, but in none of the eight adenomas/dysplasia with MSI-H phenotype (P = 0.009). Our results indicate that somatic mutation of the APC gene plays an important role in the pathogenesis of gastric adenoma and dysplasia but has a limited role in neoplastic progression to adenocarcinoma. Gastric adenomas or dysplasias without APC mutations but with or without MSI may have a different biological behavior, and are precursors of intestinal-type of gastric adenocarcinomas.

Development of an Aggressive Depressed Cancer in a Case of Familial Adenomatous Polyposis

In 1977, Kariya et al. reported a case of a small depressed cancer in a patient with familial adenomatous polyposis (FAP) raising the possibility that not all cancers in FAP develop from polypoid adenomas. It is now becoming widely recognized that colonic adenomas may appear as flat or depressed lesions. However, colorectal cancers developing in patients with familial adenomatous polyposis (FAP) are still thought to evolve from adenomatous polyps following the polyp-carcinoma sequence. We report the case of a patient with FAP in whom rectal carcinoma developed 23 years after subtotal colectomy and ileorectal anastomosis. We suggest that this malignancy may have developed de novo because of the depressed shape of the lesion and the aggressive growth pattern. This case raises the possibility that carcinomas may not always evolve from polyps in FAP. Aggressive cancers with a depressed appearance should be searched for when surveying the rectal stump in patients with FAP.

Colorectal carcinoma with special reference to growth pattern classifications: clinicopathologic characteristics and genetic changes.

Many colorectal carcinomas are known to develop from preexisting polypoid adenomas; however, they can also develop from so-called "flat adenomas". To elucidate the growth patterns of flat- or depressed-derived colorectal carcinomas, we investigated the clinicopathologic characteristics and genetic changes of invasive carcinomas. Seventy-five colorectal carcinomas were classified into three groups: 46 upward growth (UG) type, 22 downward growth (DG) type, and 7 lateral growth (LG) type. All of them had histologically infiltrated the submucosa (SM) and muscularis propria (MP). Ki-ras mutation was examined by polymerase chain reaction-single-strand conformation polymorphism analysis, and overexpression of p53 protein was analyzed by immunohistochemistry. No DG or LG carcinomas histologically demonstrated an adenomatous remnant, whereas UG carcinomas did (SM, 19 of 26; 73%; MP, 3 of 20; 15%). The percentage of tumors existing in the right colon was significantly higher in LG carcinomas (71%) than in the UG type (28%; P = 0.037). The frequency of Ki-ras mutation was significantly higher in the UG carcinomas than in the DG and LG carcinomas (52% vs 0%; P < 0.0001; and vs 0%; P = 0.014). However, the frequency of this mutation in SM-UG carcinomas with an adenomatous remnant (9 of 19; 47%) did not differ significantly from that in SM-UG carcinomas without an adenomatous remnant (3 of 7; 43%). The frequency of p53 overexpression did not differ among UG (57%), LG (57%), and DG (50%) carcinomas. These results suggest that UG carcinomas develop on the basis of the adenoma-carcinoma sequence, while the development of DG and LG carcinomas is different from that of UG carcinomas.

Prevalence and distinctive biologic features of flat colorectal adenomas in a North American population

To assess the prevalence of flat and depressed (F&D) colorectal adenomas in the United States, we performed a prospective study of 211 American patients. Dye-assisted colonoscopy was performed in the presence of both an American and a Japanese investigator. F&D lesions were found in 22.7% of patients, and these were more likely to be adenomatous than polypoid lesions (82% vs. 67%; P = 0.03) and contained more invasive cancer (4.5% vs. 0%; P = 0.04), which also appeared to be at a disproportionately advanced stage. The average size of all F&D advanced lesions (high-grade dysplasia and cancer) was significantly smaller than comparable polypoid lesions (10.75 +/- 2.7 mm vs. 20 +/- 2.9 mm; P < 0.05). F&D adenomas showed significantly stronger fragile histidine triad (FHIT) expression and lower p53 reactivity than similarly sized polypoid adenomas, whereas proliferative and apoptotic indices were similar in both groups. We conclude that there is a significant prevalence of colonic F&D colorectal adenomas in this country and that these lesions have significantly different biologic features than polypoid lesions. The clinical and epidemiologic implications of these findings for American patients need to be addressed in further studies.

Flat and polypoid adenomas of the colon and rectum: Comparison of clinicopathological characteristics and malignant potential

Flat and polypoid adenomas of the colon and rectum: Comparison of clinicopathological characteristics and malignant potential

Evolution of alachlor-induced nasal neoplasms in the Long-Evans rat.

The chloracetanilide herbicide alachlor (2-chloro-2',6-diethyl-N-(methoxymethyl)-acetanilide) induces nasal neoplasms in rats following chronic dietary exposure. The present study sought to identify the cellular origin and mechanisms of tumor induction and progression. Male Long-Evans rats were fed alachlor (0 or 126 mg/kg/day) beginning at 6 weeks of age. Following 1 month of alachlor ingestion, neither histological abnormalities nor enhanced cell division (assessed by BrdU incorporation) occurred in any region of the nasal cavity. Six months of alachlor exposure resulted in proliferation of basal and nonbasal cells in the olfactory mucosa while inducing nasal masses in 7 of 15 animals. Tumors ranged from dysplastic plaques to polypoid adenomas and originated in the olfactory regions of the nasal cavity. Neoplasms were associated with regions of respiratory metaplasia and were often covered with a low cuboidal, poorly ciliated epithelium. Tumor cells did not express characteristics of the olfactory mucosa, including olfactory marker protein (OMP, for neurons) and NMa (antibody recognizing cytochrome P450 [CYP] 2A3, found in Bowman's glands). Sites of plaque and tumor development coincided with regions of NMa immunoreactivity. These data suggest that local metabolism is important in alachlor-induced olfactory tumors and support the concept that metaplastic respiratory epithelial cells give rise to the observed neoplasms.

4498 Malignant potential of colorectal flat adenoma.

Background: Colorectal flat adenoma, meaning that their growth above the muscularis mucosa is no more than two times the thickness of the normal mucosa or height is less than 1/2 or 1/4 of longest diameter of adenoma, has been the focus of attention because of its higher malignant potential compared to polypoid adenoma. Aim: We wanted to evaluate the clinicopathological characteristics of flat adenomas and to analyze the factors associated with malignant transformation of colorectal flat adenomas. Subjects and Methods: From Jan. 1991 to Jul. 1999, 115 flat adenomas larger than 5 mm were diagnosed in 87 patients (63 male and 24 female) by colonoscopy. Adenomas equal or smaller than 5 mm was excluded because of difficulty in differentiation of flat and sessile lesions. Of those, 24 and 5 patients had a history of colorectal polyp and cancer, respectively. Mean age of the patients was 61 years (range: 36-79). Half of the patients had synchronous adenoma and 12% had a synchronous carcinoma of the colorectum. Results: The rectum (32%) was the most common site of flat adenoma, followed by sigmoid (19%), transverse (18%) and ascending colon (15%). Half of the flat adenomas were small (6-10 mm), 28% were 11-20 mm and remainder (23%) were larger than 20 mm. The surface was smooth in 56%, granular in 20% and nodular in 24%. Histologically, 70%, 21% and 5% of flat adenomas were tubular, tubulovillous, and villous adenoma, respectively. Five lesions were composed of carcinoma without any adenomatous tissue. High-grade dysplasia, intramucosal carcinoma and invasive carcinoma were diagnosed in 10%, 8% and 6% of flat adenomas, respectively. Univariate analysis demonstrated that distal location, larger size, nodular surface pattern, and villous histologic type of flat adenomas were factors associated with malignant transformation in terms of intramucosal carcinoma or invasive carcinoma. However, the size of flat adenomas was revealed as the only significant risk factor for malignancy in multivariate analysis. Conclusion: Flat adenoma of colorectum is a real disease entity and it has a relatively high malignant potential. Therefore, colonoscopic recognition of flat adenoma may play an important role for primary and secondary prevention of colorectal carcinoma.

Somatic mutations of theAPC,KRAS, andTP53 genes in nonpolypoid colorectal adenomas

Colorectal adenomas are macroscopically visible morphological changes of the mucosa that can develop focal carcinoma in the absence of surgical intervention. The successive molecular changes proposed to occur at different stages in the adenoma-carcinoma sequence were primarily based on DNA studies of exophytic, polypoid-type adenomas. Not all colorectal lesions, however, display an exophytic phenotype and a presumed distinct colorectal neoplasm, the nonpolypoid adenoma, was subsequently described as a precursor of colorectal cancer. The low incidence of KRAS mutations in nonpolypoid colorectal adenomas reported previously suggested a different genetic basis for the transformation process in these lesions. We have pursued the identification of genetic changes in benign sporadic nonpolypoid colorectal adenomas in a selected Swedish patient group with no family history of colorectal cancer. Mutation screening of the adenomatous polyposis coli (APC), KRAS, and TP53 genes was conducted using the protein truncation test, heteroduplex-single-strand conformation polymorphism analysis, and denaturing gradient gel electrophoresis on PCR-amplified fragments. Fourteen mutations in the APC gene were characterized in 10/20 samples. Mutations in the KRAS and TP53 genes were identified in 3/57 and 4/51 adenomas, respectively. The mutation frequencies and distribution of mutations in APC correlate with published data on exophytic adenomas. The low mutation frequency of the TP53 gene is consistent with the benign nature of the research material. KRAS activation (an early event in polypoid colorectal adenomas) apparently does not play a significant role in nonpolypoid adenoma development but may result in the development of a polypoid configuration. Genes Chromosomes Cancer 27:202-208, 2000.

Involvement of APC and K-ras mutation in non-polypoid colorectal tumorigenesis.

The aim of this study was to clarify the role of APC and K- ras mutations in non-polypoid colorectal tumorigenesis. DNA from 63 adenomas (31 polypoid, 17 superficial elevated, 15 superficial depressed), 66 submucosally invasive carcinomas (47 polypoid, 19 non-polypoid) and 34 advanced carcinomas were examined for K- ras codon 12 point mutations and APC mutations in the mutation cluster region. K- ras mutation: the frequency in superficial depressed adenomas was lower than that in polypoid adenomas (0% vs 31%: P = 0.018). The frequency in non-polypoid carcinomas was lower than that in polypoid carcinomas (11% vs 56%: P = 0.0008), and was relatively low compared with that in polypoid adenomas (11% vs 31%). APC mutation: the frequency in superficial depressed adenomas was lower than that in polypoid adenomas (7% vs 43%: P = 0.016), and that in polypoid carcinomas was similar to that in non-polypoid carcinomas. Polypoid adenomas, polypoid carcinomas and advanced carcinomas had almost the same frequency. There may be some pathway other than the conventional adenoma-carcinoma sequence in development of non-polypoid carcinomas. The precursors of most non-polypoid carcinomas are considered to be de novo or superficial depressed adenomas. In this non-polypoid pathway, APC mutation seems to be requisite but K- ras mutation not. It is possible that new APC mutations are acquired after the development of superficial depressed adenomas. © Copyright 2000 Cancer Research Campaign

Multiple APC mutations in sporadic flat colorectal adenomas

Adenomas are established pre-malignant lesions in colorectal carcinogenesis. To date the adenoma-carcinoma sequence for the development of colorectal carcinoma (CRC) has been based largely on molecular data of exophytic, polypoid-type adenomas. Subsequently, a different type of adenoma has been identified: the flat adenoma, so called for its flat, non-exophytic appearance, making it less likely to be detected during conventional endoscopy. However, due to technological advances in endoscopic methods, flat-type adenomas can now frequently be detected and are no longer considered rare colorectal lesions. The phenotype of flat colorectal adenomas differs macroscopically and histologically from exophytic adenomas. Flat colorectal adenomas, as a rule, are tubular structures often revealing high-grade dysplasia, irrespective of the size or villous component. Flat adenomas have also been recognised as pre-cancerous lesions in gastric cancer. Unlike the wealth of clinical and molecular information available for polypoid (exophytic) adenomas, molecular profiles of flat-type lesions have not yet been characterised systematically and the full clinical significance hereto realised. Previous molecular investigation of the K-ras gene in flat colorectal adenomas suggests a distinct pathway in their development. In this study, mutation analysis of the adenomatous polyposis coli (APC) gene using the protein truncation test (PTT) in 20 flat colorectal adenomas in a selected group of 16 patients without hereditary predisposition to colorectal cancer, revealed double truncations of the APC gene in four adenomas. In one of these adenomas a third mutation was detected by DNA sequence analysis.

Depressed adenoma of the duodenum in patients with familial adenomatous polyposis

Depressed neoplastic lesions of the colorectum have been specified in patients with familial adenomatous polyposis (FAP). The aim of this study was to characterize endoscopic, histologic, and immunohistochemical features of depressed adenoma of the duodenum in patients with FAP.Duodenoscopy was performed on 25 patients with FAP, and the neoplastic nonampullary lesions were classified as polypoid or depressed adenomas. The grade of dysplasia, the proliferative activity determined by Ki-67 labeling index (LI), and the grade of p53 expression were compared between polypoid and depressed neoplasia.Ten subjects had depressed nonampullary adenoma, whereas polypoid adenoma was found in the remaining 15 subjects. Moderate dysplasia was more frequent in depressed adenoma than in polypoid adenoma (70% vs. 27%, P = 0.04). Whereas p53 expression was not different between the two adenoma groups, the LI was significantly higher in depressed adenoma than in polypoid adenoma (59.7 +/- 9.5 vs. 47.5 +/- 10.7, P < 0.01).Depressed adenoma of the duodenum is a distinctive phenotype of duodenal neoplasm in patients with FAP. The high proliferative activity of depressed adenoma suggests that there may be a need to survey FAP patients with such lesions intensively.

Familial gigantiform cementoma.

Familial gigantiform cementoma is a rare autosomal dominant tumor that is benign but can result in disfigurement of the facial skeleton. Two families with a total of five patients presented for treatment. Because of a lack of opportunity to obtain treatment early, three of the patients presented in adult life with massive tumors requiring extensive resection and complex reconstruction in multiple stages. The two female patients had chronic anemia caused by multifocal polypoid adenomas of the uterus and required hysterectomy before treatment. The last three patients had elevated alkaline phosphatase levels before tumor resection, and these levels decreased after surgery. With extensive resection of the tumors and reconstruction of both the soft tissues and facial skeleton, good functional and aesthetic results can be obtained. There has been no tumor recurrence with 3 years of follow-up.

Non-Polypoid Adenomas of the Colon Are Associated with Subjacent Lymphoid Nodules: An Experimental Study in Rats

Background: Subjacent lymphoid nodules (SLNs) have been found in 38% of non-polypoid colonic adenomas in humans. In the present work the presence of SLNs in experimentally induced colonic adenomas was investigated in rats. Methods: 1,2-Dimethylhydrazine was injected subcutaneously in 290 Sprague-Dawley rats for 27 weeks. Results: An SLN was present in 28.6% of the 84 adenomas, in 8.4% of the 119 adenocarcinomas, and in 9.7% of the 31 small carcinomas without remnant adenomatous tissue. An SLN was found in 35.6% of the 59 non-polypoid neoplasias but only in 9.1% of the 175 polypoid (that is, exophytic) neoplasias. When only adenomas were considered, SLNs were present in 50.0% of the 34 non-polypoid adenomas but only in 14.0% of the 50 polypoid adenomas. Conclusions: Non-polypoid colonic adenomas evolve preferentially from the minimal fraction of the colonic mucosa that overlays the few existing lymphoid nodules in rats.

Activation of the ras genes in malignant and premalignant colorectal tumors.

The activation of ras genes has been established as one of the steps in the process of colon tumorigenesis. These genes are converted into active oncogenes by point mutations in codons 12, 13, and 61, although a more complex way has also been shown, through alteration of gene expression. In order to investigate the spectrum of ras gene mutations, we examined 78 colorectal polypoid adenomas and 76 primary colorectal adenocarcinomas for codon 12 point mutations in K-, H- and N-ras, using a PCR-RFLP assay. K-ras mutations were found in 42.3% (33/78) of adenomas and in 36.8% (28/76) of carcinomas. Statistically significant association (p=0.043) was found between the frequency of K-ras mutations in mixed adenomas larger than 2 cm, compared to smaller mixed adenomas. On the other hand, adenocarcinomas harbored more frequently mutations, when indicating development from adenoma (p=0.016), in higher grade of differentiation (p=0.001) and in females with tumor located proximal to the rectosigmoid (p=0.013). No mutations were found in H-ras. The incidence of N-ras mutations was 1.3% in adenomas and adenocarcinomas (1/78 and 1/76 respectively). Based on our results, we propose the possibility that K-ras-dependent tumor development results in the formation of less aggressive neoplasms, than the process of K-ras-independent carcinogenesis. Our findings and other previous reports indicate that K-ras mutations might be a secondary stress-effect from extrinsic or intrinsic stimulatory factors and that these mutations are not necessarily involved in the malignant transformation of the cell.