Biomedical subjects

Masakazu Yashiro

Publications and source records attributed to Masakazu Yashiro.

At least 19 recordsLinked to original sources

PubMed2007

Selective cyclooxygenase-2 inhibitor downregulates the paracrine epithelial-mesenchymal interactions of growth in scirrhous gastric carcinoma.

The importance of cancer-mesenchymal interactions in the aggressive behavior of scirrhous gastric cancer is supported by experimental and clinical evidences. We have previously reported that gastric fibroblasts secretion of keratinocyte growth factor (KGF) underline the remarkable proliferation of scirrhous gastric cancer cells. Cyclooxygenase-2 (COX-2) is not only expressed in cancer cells, but also in interstitial fibroblasts in gastric carcinoma. To clarify the mechanisms responsible for the antiproliferation effect of COX-2 inhibitors, effect of COX-2 inhibitor on the paracrine epithelial-mesenchymal interactions of growth was examined. Scirrhous gastric cancer cell line, OCUM-2M, gastric fibroblasts, NF-21, and COX-2 inhibitor, JTE-522, were used. Growth-interaction was examined by calculating the number of cancer cells or by measuring [(3)H] thymidine incorporation of cancer cells. Effect of JTE-522 on KGF expression from NF-21 cells and OCUM-2M cells was analyzed by ELISA and RT-PCR. The conditioned medium from gastric fibroblasts significantly stimulated the growth of scirrhous gastric cancer cells. JTE-522 at the concentrations of 10(-5) and 10(-6) M significantly decreased the growth-stimulating activity of gastric fibroblasts. JTE-522 reduced the expression of KGF mRNA and the production of KGF from gastric fibroblasts. Oral administration of JTE-522 significantly decreased the size of xenografted tumor coinoculated with OCUM-2M cells and NF-21 cells in nude mice. JTE-522 decreased COX-2 expression and Ki67 labeling index within the coinoculated tumor. These findings suggested that a selective COX-2 inhibitor, JTE-522, downregulates KGF production from gastric fibroblasts, resulting in the inhibition of paracrine epithelial-mesenchymal interactions of proliferation between scirrhous gastric cancer cells and gastric fibroblasts.

Animals↗

PubMed2006

A novel molecular targeting compound as K-samII/FGF-R2 phosphorylation inhibitor, Ki23057, for Scirrhous gastric cancer.

BACKGROUND & AIMS: Scirrhous gastric carcinoma carries the highest mortality of all gastric cancers. The poor prognosis is reported to be associated with K-samII amplification, which encodes fibroblast growth factor receptor type 2 (FGF-R2). Ki23057, a newly developed small molecule-acting K-samII/FGF-R2 autophosphorylation inhibitor, is a tyrosine kinase inhibitor that competes with adenosine triphosphate for the binding site. The aim of the current study is to clarify the possibility of molecular target therapy with Ki23057 for treating scirrhous gastric cancer. METHODS: Five human gastric cancer cell lines were used. OCUM-2MD3 and OCUM-8 were derived from scirrhous carcinomas. MKN-7, MKN-45, and MKN-74 cells were derived from nonscirrhous carcinomas. In vitro effects of Ki23057 on cell growth were determined by calculating the number of cancer cells. The influences of Ki23057 on the mitogen-activated protein kinase and phosphatidylinositol 3 kinase signaling pathways and the apoptosis pathway in the gastric cancer cells were also examined. For in vivo experiments, the Ki23057 was administered orally to mouse models of peritoneal dissemination. RESULTS: K-samII amplification was found in OCUM-2MD3 and OCUM-8 cells but not in MKN-7, MKN-45, or MKN-74 cells. Ki23057 significantly inhibited the proliferation of scirrhous cancer cells but not nonscirrhous gastric carcinoma cells. Ki23057 decreased phosphorylation of K-samII/FGF-R2, extracellular signal-regulated kinase, and Akt and increased apoptosis in scirrhous cancer lines. The oral Ki23057 administration significantly (P < .001) prolonged survival of mice with peritoneal dissemination following injection of OCUM-2MD3 scirrhous cancer cells. CONCLUSIONS: A novel K-samII/FGF-R2 phosphorylation inhibitor, Ki23057, appears therapeutically promising in scirrhous gastric carcinoma with K-samII amplification.

Adenocarcinoma, Scirrhous↗

PubMed2006

Decreased expression of the adhesion molecule desmoglein-2 is associated with diffuse-type gastric carcinoma.

Desmoglein-2 (Dsg2) is one of the components of the cell-cell adherence junction. We previously reported that loss of heterozygosity at chromosome 18q12, on which the Dsg2 gene exists, is frequently found in diffuse-type gastric cancers. This study investigated the relationship between Dsg2 expression and diffuse-type gastric cancers. A total of 112 primary tumours resected from patients with gastric cancer were stained with a monoclonal antibody against Dsg2 and examined for correlations between the expression of Dsg2 and various clinicopathological factors, including loss of heterozygosity on chromosome 18q and prognosis. Dsg2 is immunolocalised at cell-cell boundaries in normal gastric mucosa. Loss of Dsg2 expression was observed in 33 of 112 gastric tumours. There was a statistically significant correlation between a decrease in Dsg2 staining and loss of tumour differentiation (P < 0.001), tumour macroscopic feature (P < 0.001) and peritoneal dissemination (P = 0.023), and Dsg2-negative staining was correlated significantly with loss of heterozygosity on chromosome 18q12 (P = 0.001). The prognosis of patients with Dsg2-negative tumours was significantly worse than that of those with Dsg2-positive tumours (log rank, P < 0.01), while multivariate analysis revealed that Dsg2 was not an independent prognostic factor. These findings suggest that decreased expression of Dsg2 is associated with diffuse-type gastric cancers and poor prognosis in gastric carcinoma.

Cadherins↗

PubMed2006

Synergic antiproliferative effect of DNA methyltransferase inhibitor in combination with anticancer drugs in gastric carcinoma.

Epigenetic alterations of DNA methylation play an important role in the regulation of gene expression associated with chemosensitivity of gastric carcinomas. With the aim of improving the chemotherapeutic efficacy of gastric carcinoma, the effect of DNA methyltransferase inhibitor, 5-aza-CdR, on the chemosensitivity of five anticancer drugs was investigated. Human gastric cancer cell lines, OCUM-2M and MKN-74, and five anticancer drugs, 5-FU, PTX, OXA, SN38, and GEM, were used. In both gastric cancer cell lines, a synergistic antiproliferative effect by a combination of 5-aza-CdR at 5 microM was found in SN38 and GEM. 5-Aza-CdR at 5 microM increased apoptosis induced by SN38 and GEM in both cell lines. 5-Aza-CdR increases the expression of DAPK-2 and DAPK-3, RASSF1, and THBS1 genes in both OCUM-2M and MKN-74 cells, but not that of hMLH1, p16, MGMT, E-cadherin, and p53 genes. These findings suggest that 5-aza-CdR is a promising chemotherapeutical agent for gastric carcinomas, in combination with the anticancer drugs SN38 and GEM, in apoptosis signaling. The upregulation of DAPK-2 and DAPK-3, RASSF1, and THBS1 genes by 5-aza-CdR might be associated with the synergistic effect.

Antineoplastic Agents↗

PubMed2006

Preclinical study of a "tailor-made" combination of NK4-expressing gene therapy and gefitinib (ZD1839, Iressa) for disseminated peritoneal scirrhous gastric cancer.

We evaluated the effect of a "tailor-made" chemo-gene therapy in scirrhous gastric cancer (SGC)-bearing nude mice. For this tailor-made approach, we first selected gefitinib (epidermal growth factor receptor-tyrosine kinase inhibitor)-sensitive SGC cell lines, and 5/8 cell lines demonstrated various degrees of gefitinib-sensitivity. In the highly gefitinib-sensitive NUGC-4, the biological response to NK4 (HGF antagonist/angiogenesis inhibitor) was examined. Subsequently, the composition of an NK4-expressing ternary complex (cationic lipid/nucleic acid/HMG-1, 2 protein) was optimized for maximum transfection activity in NUGC-4. Finally, mice were peritoneally coinoculated with NUGC-4 and scirrhous-associated gastric fibroblasts, NF22, on day 0. Animal models were orally administrated gefitinib (50 mg/kg/day, on days 7-28), and peritoneally NK4-expressing ternary complex (on days 14, 21 and 28). NK4-expression suppressed the gefitinib-resistance induced by the interaction between fibroblasts and SGC, and eventually, this tailor-made combination synergistically decelerated the disease progression by inhibiting proliferative, angiogenic and antiapoptotic effects in tumor tissues. On day 28, both the hemoglobin concentration (g/dl) (control (n = 8), 11.9; treated (n = 8), 17.3; p = 0.0014) and the numbers of mice in good condition (control, 2; treated, 8; p = 0.0012) were significantly greater, and the abdominal girth (mm) (control, 81.1; treated, 70.3; p = 0.0036) was significantly reduced. The median points of bloody ascite-free survival time (days) (control, 22; treated, 44; p < 0.0001) and time to euthanasia (days) (control, 36.5; treated, 56; p < 0.0001) were also significantly prolonged. This combination is a potentially useful approach to the treatment of peritoneal gefitinib-sensitive SGC dissemination.

Adenocarcinoma, Scirrhous↗

PubMed2006

A synergic inhibitory-effect of combination with selective cyclooxygenase-2 inhibitor and S-1 on the peritoneal metastasis for scirrhous gastric cancer cells.

An inhibitory-effect of a selective cyclooxygenase-2 (COX-2) inhibitor on peritoneal metastasis of scirrhous gastric carcinoma was investigated in vivo. Peritoneal metastasis had developed after intraperitoneal inoculation of scirrhous gastric cancer cells, OCUM-2MD3, in nude mice. COX-2 inhibitor and/or S-1 were administered orally in nude mice with peritoneal metastasis. Oral administration of COX-2 inhibitor and S-1 significantly prolonged survival rates of these nude mice, compared with either alone. These findings suggested that combining S-1 and COX-2 inhibitor administration obtain a synergistic inhibitory-effect on the peritoneal metastasis of scirrhous gastric carcinoma.

Adenocarcinoma, Scirrhous↗

PubMed2006

Synchronous adenocarcinomas of the ileum and transverse colon detected by capsule endoscopy: report of a case.

A 77-year-old woman was admitted to our hospital with anemia and anorexia. Neither gastrointestinal endoscopy nor computed tomography showed by abnormal findings; however, a capsule endoscopy, performed to detect obscure gastrointestinal bleeding, revealed a tumor in the ileum. When we tried to take biopsies of the ileal tumor by push enteroscopy via the anus, we found another tumor in the transverse colon. On exploration, tumors were identified in the ileum and the transverse colon. Thus, we resected the ileum and transverse colon with regional lymph node dissection. Histologic sections from both the ileum and colon revealed moderately differentiated adenocarcinomas with no lymph node metastasis.

Adenocarcinoma↗

PubMed2006

Frequent p16 CpG island hypermethylation in primary remnant gastric cancer suggesting an independent carcinogenic pathway.

Cancer found in the post-operative remnant stomach includes both newly developed cancer after surgery for benign-disease (PRC) and metachronous multiple cancer (MRC). Differences in the carcinogenic pathway between PRC and MRC have been suspected from clinical studies. However, no study has demonstrated the difference in molecular alteration between these diseases. P16 is inactivated predominantly by epigenetic change, rather than genetic alteration. We analyzed the methylation status and protein expression of the p16 gene in cancers of the remnant stomach. Eleven lesions of PRC, 24 lesions of MRC and corresponding non-cancerous tissue, as well as 13 primary gastric cancer (PC) lesions were examined. DNA was extracted by the micro-dissection method from paraffin-embedded surgical specimens. The methylation status of the promoter CpG island of the p16 gene was examined by using a methylation-specific polymerase chain reaction technique. To detect protein expression, immunohistochemical staining was employed. p16 promoter hypermethylation was observed more often in remnant gastric cancer than in PC. A significantly more frequent hypermethylation in the p16 gene was found in PRC (64%) than in MRC (21%) or PC (23%). Moreover, a significant correlation was found between p16 promoter hypermethylation and diminishment of protein expression in cancers of the remnant stomach. Silencing of the p16 gene by methylation of its promoter CpG island was suggested as a unique molecular mechanism in the carcinogenesis of PRC compared with MRC or PC.

Aged↗

PubMed2006

Histone deacetylase inhibitor, trichostatin A, increases the chemosensitivity of anticancer drugs in gastric cancer cell lines.

Epigenetic alterations of the histone acetylation play an important role in the regulation of gene expression associated with cell cycles and apoptosis that may affect the chemosensitivity of gastric carcinomas. Recently, a histone deacetylase inhibitor, trichostatin A (TSA), was proven to be a chemo-sensitizer on human erythroleukemia cells. With the aim of improving the chemotherapeutic efficacy of gastric carcinoma, the effect of TSA on the chemosensitivity of several anticancer drugs in gastric carcinoma cells was investigated. Human gastric cancer cell lines, OCUM-8 and MKN-74, and 5 anticancer drugs, 5-fluorouracil (5-FU), paclitaxel (PTX), oxaliplatin (OXA), irinotecan (SN38) and gemcitabine (GEM) were used. In both gastric cancer cell lines, a synergistic anti-proliferative effect by the combination of TSA (30 ng/ml) with 5-FU, PTX or SN38 showed a synergistic anti-proliferative effect in OCUM-8 and MKN-74 cells. TSA increases the expression of p21, p53, DAPK-1 and the DAPK-2 gene in both OCUM-8 and MKN-74 cells. In conclusion, TSA is a promising chemotherapeutical agent in combination with anticancer drugs of 5-FU, PTX and SN38 in gastric cancer cell lines. The up-regulation of p53, p21, DAPK-1 and DAPK-2 might be associated with the synergistic effect of TSA.

Antineoplastic Agents↗

PubMed2006

[A case of advanced gastric cancer with malignant ascites responding to weekly paclitaxel therapy].

A 54-year-old woman with scirrhous gastric cancer in the upper third area was admitted to our hospital. She was diagnosed with advanced gastric cancer that was inoperable due to peritoneal metastasis, so weekly paclitaxel (PTX) therapy was carried out. After 2 courses, malignant ascites completely disappeared and bilateral hydronephrosis improved. After 4 courses, no ascites or hydronephrosis were seen. Only neutropenia (grade 2) and alopecia (grade 1) were observed as adverse events during the therapy, but no major adverse events were noted. We also investigated the concentration of paclitaxel in ascites. Two hours after intravenous injection of PTX, the concentration of PTX in ascites rose over the reported cytotoxic dose of PTX, and this available concentration was maintained after 48 hours. Weekly paclitaxel therapy is suggested to be one of the safe and useful treatments for advanced gastric cancer with malignant ascites.

Adenocarcinoma, Scirrhous↗

PubMed2005

Frequent microsatellite instability in primary esophageal carcinoma associated with extraesophageal primary carcinoma.

Patients with esophageal squamous cell carcinoma (ESCC) frequently develop other primary cancers, such as gastric cancer and head and neck cancer. Details of carcinogenesis in patients with multiple primaries that include esophageal carcinoma with other primary carcinoma (ECOPC) remain uncertain. We examined microsatellite instability (MSI) status, frameshift mutation in target genes of MSI, mismatch repair protein expression and hypermethylation of the hMLH1 promoter region in ECOPC patients to better understand the underlying carcinogenic processes. High frequency MSI (MSI-H) was found in 15 (44.1%) of 34 patients with ECOPC, but in only 6 (14.3%) of 42 patients with esophageal cancer alone (p < 0.01). Frameshift mutations in TGFbetaRII, BAX, MSH3 and MSH6 genes respectively were present in 4, 1, 2 and 2 of 34 ECOPC patients. Immunohistochemical study showed that 12 (80.0%) of 15 MSI-H tumors showed loss of expression of either hMLH1 or hMSH2. In addition, 6 of 9 tumors (66.7%) that showed reduced hMLH1 expression also had hypermethylation of the hMLH1 promoter region. Our findings suggested that carcinogenesis in ECOPC was closely associated with the MSI pathway because of mismatch repair protein deficiency.

Adaptor Proteins, Signal Transducing↗

PubMed2005

A novel high-specificity approach for colorectal neoplasia: Detection of K-ras2 oncogene mutation in normal mucosa.

There is an important need for a high-specificity approach to colorectal cancer. Approximately 50% of colorectal tumors contain K-ras gene mutations, which occur as an early step in carcinogenesis. K-ras mutations were detectable not only in tumors but also in microscopically normal colorectal mucosa close to carcinomas in some patients with colorectal cancer. This is the first systematic analysis of K-ras mutations in normal colonic mucosa at multiple consistently-selected locations. A total of 480 normal colonic mucosal samples were obtained from 80 subjects, including 65 patients with sporadic colorectal cancer and 15 controls in whom a colorectal neoplasm was ruled out endoscopically. Normal mucosal samples were obtained at multiple consistently-selected locations using biopsy forceps during colonoscopy. Mutant allele-specific amplification (MASA)-PCR was performed; this could detect a K-ras mutation in normal colonic mucosa even though it was only sparsely present. The K-ras mutation was found in histologically normal mucosa from colorectal cancer patients (20 of 65 cases; 41 of 390 loci) by MASA-PCR, especially frequent (51%; 19 of 37 cases) when the tumor showed a K-ras mutation. In contrast, no mutation was found in normal mucosa from 15 controls (90 loci). K-ras mutation in normal mucosa showed a significant association with the presence of colorectal cancer (p = 0.008). The specificity of the MASA-PCR method for colorectal neoplasms was thus 100%. We conclude that detection of K-ras mutations in normal colonic mucosa might serve as a high-specificity approach to colorectal cancer.

Colon↗

PubMed2005

Effect of organ-specific fibroblasts on proliferation and differentiation of breast cancer cells.

Breast carcinomas contain both tumor cells and stromal cells, including fibroblasts, endothelial cells, and lymphocytes. Proliferation of breast cancer cells may be controlled partly by mesenchymal cells, especially fibroblasts. We studied effects of fibroblasts on tumorigenicity and histologic features of breast cancer cells vivo, and analyzed fibroblast-produced growth-promoting factors in vitro. Breast carcinoma cells from four lines, and fibroblasts from lines obtained from skin and breast tissue of four patients with breast cancer were used. A suitable number of breast tumor cells and fibroblasts were inoculated subcutaneously into nude mice; resulting tumors were examined. Then conditioned medium from fibroblasts was added to cultures of breast cancer cells to study growth effects, and growth-promoting factors from breast fibroblasts were analyzed. Co-inoculation of breast cancer cells with breast fibroblasts into mice significantly increased tumorigenicity and tumor size beyond those obtained with breast cancer cells alone. Histologically, tumors resulting from co-inoculation with breast fibroblasts showed a scirrhous pattern with extensive fibrosis, while those formed by breast cancer cells injected alone or co-inoculation with skin fibroblasts showed a solid pattern. Medium from breast fibroblasts significantly increased breast cancer cell growth in vitro, while the various skin fibroblasts did not all show this effect. Structural and functional interactions between organ-specific fibroblasts and breast cancer cells may importantly regulate breast cancer growth and progression.

Animals↗

PubMed2005

CD54 expression is predictive for lymphatic spread in human gastric carcinoma.

Even among gastric carcinoma cases with a similar extent of lymphatic invasion, the number of diseased lymph nodes may vary. Other factors might also contribute to the process of lymphangitic metastasis. Primary gastric tumors with the same extent of pathologic lymphatic invasion were studied in 78 patients. We investigated the correlation between CD54 expression on cancer cells and clinicopathologic features. Decreased CD54 expression on cancer cells was significantly correlated with the number of involved lymph nodes and the extent of lymph node spread. The number of diseased lymph nodes was associated with the prognosis of patients with gastric carcinoma. The CD54-negative group had a significantly worse prognosis than the CD54-positive group. These findings suggested that CD54 expression is predictive for lymphatic spread and prognosis in human gastric carcinoma.

Adult↗

PubMed2005

Up regulation of ICAM-1 gene expression inhibits tumour growth and liver metastasis in colorectal carcinoma.

We have previously reported that decreased intercellular adhesion molecule-1 (ICAM-1) expression in cancer cells is associated with liver metastasis of colorectal cancer. In this study, we have investigated the effect of ICAM-1 gene transfection into the human colorectal cancer cell line LM-H3 on cell adhesiveness and cytotoxicity of peripheral blood mononuclear cells (PBMC) to cancer cells. Furthermore, we have investigated the effects of this gene transfer on subcutaneous tumour and liver metastases of LM-H3 in nude mice. More PBMC adhered to ICAM-1 transfected LM-H3 cells, LM-H3/ICAM-1, than to non-transfected LM-H3 cells and control LM-H3/Vector. Lysis of LM-H3/ICAM-1 cells by PBMC was significantly increased compared with LM-H3/Vector. Liver metastases with LM-H3/ICAM-1 cells were fewer in number and smaller than metastases with LM-H3/Vector. Intra-tumoural injection of ICAM-1 adenoviral vector significantly inhibited the growth of subcutaneous LM-H3 tumour. In conclusion ICAM-1 gene transfection using adenovirus vector might be an effective therapy for liver metastasis of colorectal carcinoma.

Adenoviridae↗

PubMed2005

K-ras mutation influences macroscopic features of gastric carcinoma.

INTRODUCTION: Gastric carcinoma is classified morphologically as type 1 to 4. Type 1 is defined as a polypoid tumor; types 2 and 3 are defined as ulcerated tumors with polypoid growth or gastric wall infiltration, respectively, and type 4 tumors are defined as flat. This morphological classification is important because biological characteristics differ between the four morphological types, but little is known about genetic differences between them. MATERIALS AND METHODS: One hundred eight gastric tumors were classified macroscopically as type 1 to 4. Tumoral DNA was microdissected from paraffin-embedded tissue sections. PCR amplification of exon 1 of a K-ras containing codons 12 and 13 was performed. K-ras amplicons were dot-blotted onto nylon filters and hybridized with radiolabeled oligomer primers. RESULTS: A K-ras mutation was found in 20 of 108 gastric cancers. A significant relationship of K-ras mutation with polypoid cancer was found. The frequency of K-ras mutation was 6/14 (43%), 8/29 (28%), 2/11 (18%), and 4/54 (7%) in type 1 to 4 tumors, respectively. K-ras mutation was correlated with well-differentiated tumors. Of various types of K-ras mutations, 12 Asp often was seen in type 1 and 2 gastric cancers (well-demarcated, elevated tumors), while 12 Val and 12 Ser were often seen in type 3 and 4 cases (infiltrating carcinomas). CONCLUSION: K-ras mutations occur prominently in type 1 and type 2 gastric cancers.

Adenocarcinoma↗

PubMed2005

Inhibitory effect of a selective cyclooxygenase inhibitor on the invasion-stimulating activity of orthotopic fibroblasts for scirrhous gastric cancer cells.

The cyclooxygenase (COX)-2 inhibitor has been reported to impede the progression of gastric cancer, but underlying mechanisms remain unclear. We therefore investigated the effect of a COX-2 inhibitor, JTE-522, on the ability of orthotopic fibroblasts to stimulate invasion of scirrhous gastric carcinoma cells. The human scirrhous gastric cancer cell lines OCUM-2D or OCUM-2M, and human gastric fibroblasts (NF-21) were cultured in the absence or presence of JTE-522 at various concentrations. Cancer cells were then assayed for invasiveness in vitro by invasion assay. The effect of prostaglandins (PG) on growth factor production in NF-21 cells was examined by ELISA. Finally, the effects of orally administrated JTE-522 on orthotopically transplanted tumors were examined in nude mice. NF-21 cells stimulated invasion by OCUM-2D cells, an effect suppressed by JTE-522 at 5 x 10(-6) M. Hepatocyte growth factor (HGF) and PGE2 production by NF-21 cells were suppressed by JTE-522 (P < 0.01). PGE2 stimulated HGF production by NF-21 cells in a dose-dependent manner. JTE-522 significantly suppressed orthotopic tumor growth and lymph node metastasis, and also decreased HGF expression by fibroblasts within the gastric tumor. In conclusion, we found that gastric fibroblasts stimulated invasiveness in scirrhous gastric cancer cells, whereas a selective COX-2 inhibitor inhibited this paracrine effect by decreasing fibroblast PGE2 production, resulting in downregulation of HGF production.

Adenocarcinoma, Scirrhous↗

PubMed2005

Serrated adenomas have a pattern of genetic alterations that distinguishes them from other colorectal polyps.

BACKGROUND: Serrated adenomas are characterized by serrated crypts with dysplasia, and are distinguished from other polyps by their histology, but the genetic basis of serrated adenomas is unknown. We investigated genetic alterations in colorectal polyps to determine if a specific pattern were associated with serrated adenomas. METHODS: Sixty-six small (<10 mm) colorectal polyps were studied, including 11 hyperplastic polyps, 27 serrated adenomas, 9 tubular adenomas, 6 tubulovillous adenomas, and 3 villous adenomas. Allelic imbalance and microsatellite instability were detected by analysis of microsatellites on 5q, 18q, 17p, 2p, and 3p; K-ras mutations were detected by oligonucleotide hybridization. RESULTS: Each polyp subset had its own characteristic mutational signature. Allelic imbalance of 18q was significantly more common (P < 0.05), whereas allelic imbalance of 5q and K-ras mutations were significantly less common (P < 0.05) in serrated adenomas compared with other polyps. Allelic imbalance of 17p was not found in any polyp. CONCLUSIONS: Serrated adenomas are significantly more likely to have allelic imbalance at 18q than other types of adenomas, and significantly less likely to have allelic imbalance at 5q or K-ras mutations. Serrated adenomas seem to evolve through a different genetic pathway than other types of polyps in the colon.

Adenoma↗