PURPOSE: General conceptions of carcinogenic mechanisms by recent reports are ras-p53 gene pathway in sporadic colorectal cancers (SCC), MMR gene pathway in hereditary nonpolyposis colorectal cancer (HNPCC) and APC gene in familial adenomatous polyposis (FAP). But in the colorectal cancer with multiple polyps (CCMP), the carcinogenic pathway is not still defined exactly. In order to find out the which carcinogenic pathway control the CCMP and SCC, genetic instability were studied in CCMP and SCC. METHODS: In this study, genetic instability on D2S123, D3S1029, D5S107, D6S87 and AP delta3 foci and gene mutations of hMLH1 (exon 2, 16, 19), hMSH2 (exon 11, 12, 13, 14) gene of MMR gene, p53 gene (exon 5, 6, 7, 8, 9) were studied on the 60 DNA samples of CCMP (30 cases) and SCC (30 cases). RESULTS: 1. Observed positive genetic instability was higher in CCMP (30%) than SCC (20%), and was higher in right colon cancers (33%) than left colon cancers (23%) or rectal cancers (17%), but not significant statisitically. And observed positive genetic instability was lower in moderate differentiated cancers (16%) than well (67%) or poorly (60%) differentiated cancers (P=0.005). 2. Any mutations of hMLH1 and hMSH2 gene of MMR gene were not observed in both of CCMP and SCC, but 3 cases (2 CCMPs and 1 SCC) point mutations of intron of hMSH2 gene, which were higher in positive genetic instability than negative (P=0.002). 3. This 3 cases point mutations were C for T which were on 6th bases upstream from codon 669. 4. From the results of SSCP for nucleotide sequencing of p53 gene, the abnormal bands were observed in 30% (9 of 30) of CCMP and SCC. Also the abnormal bands were observed in both of positive or negative genetic instability without differences. CONCLUSIONS: With above results the authors suggested that the mechanism of genetic instability and mutations of p53 gene strongly affect the mechanism of carcinogenesis in SCC and CCMP. And there are relationship between genetic instability and point mutation at intron region of hMSH2 gene. However further evaluation and research is needed to establish relation between APC gene and other different kind of MMR gene.
Adenomatous Polyposis Coli ; Carcinogenesis ; Codon ; Colonic Neoplasms ; Colorectal Neoplasms* ; Colorectal Neoplasms, Hereditary Nonpolyposis ; DNA ; DNA Mismatch Repair* ; Fertilization ; Genes, APC ; Genes, p53* ; Introns ; Point Mutation ; Polymorphism, Single-Stranded Conformational ; Polyps* ; Rectal Neoplasms

OBJECTIVETo analyze the mutational features of adenomatous polyposis coli (APC) gene and to explore the effect of mismatch repair (MMR) deficiency on its mutations in hereditary non-polyposis colorectal cancers (HNPCC).

METHODSPCR-based in vitro synthesized protein test (IVSP) assay and sequencing analysis were used to confirm somatic mutations of whole APC gene in 19 HNPCC patients.

RESULTSEleven cases with thirteen mutations were determined. The frequency of APC mutation was 58%(11/19). The exhibiting mutations consisted of 9 frameshift mutations and 4 nonsense ones, indicating the existence of more frameshift mutations (69%). All of frameshift mutations were deletion or insertion of 1-2 bp and most of them (7/9) happened at simple nucleotide repeat sequences, particularly within (A) n tracts (5/9). All of four nonsense mutations resulted from C to T transitions at CpG sites.

CONCLUSIONMutational inactivations of APC gene were detected in more than half of HNPCC patients in this study, indicating that APC mutation is a common molecular event in the tumorigenesis of HNPCC. According to the location of frameshift mutations at simple nucleotide repeat sequences and point mutations at CpG sites, it was suggested that endogenous mechanisms like MMR deficiency might exert an effect on the nature of APC mutations in most HNPCC.

Adenomatous Polyposis Coli ; genetics ; Adenomatous Polyposis Coli Protein ; genetics ; metabolism ; Carcinoma ; genetics ; Colorectal Neoplasms ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; Genes, APC ; physiology ; Humans

Squamous cell carcinoma of the rectum is extremely rare, with an incidence between 0.25 and 1 case per 1,000 cases of colorectal carcinoma. In familial adenomatous polyposis (FAP), characterized by the progressive development of hundreds to thousands of adenomatous colonic polyps, unscreened patients and those who are not treated at an early stage of the disease have an extremely high risk of developing colorectal adenocarcinoma. A few reports of squamous cell carcinoma of the rectum have been published but none of the patients had FAP. Here, we report the case of a 17-year-old male with FAP who developed rectal squamous cell carcinoma.
Adenocarcinoma ; Adenomatous Polyposis Coli* ; Adolescent ; Carcinoma, Squamous Cell* ; Colonic Polyps ; Colorectal Neoplasms ; Humans ; Incidence ; Male ; Rectal Neoplasms ; Rectum

PURPOSE: Restorative proctocolectomy (RP) is a standard surgery in patients with ulcerative colitis and familial adenomatous polyposis. Usually, diverting ileostomy is performed to protect an ileoanal anastomosis with RP. However, there are many controversies whether diverting ileostomy might urgently be needed. This study was performed to compare postoperative complications after RP with or without diverting ileostomy. METHODS: Between July 1994 and June 2001, 77 (M : F= 45 : 32) patients underwent RP. The indication criteria for diverting ileostomy included tension at the anastomosis, positive leakage test, compromised blood flow in the ileal pouch, long-term and high-dose steroid use, and severe rectal inflammation in ulcerative colitis patients. RESULTS: Histopathologic diagnoses revealed 45 ulcerative colitis, 23 familial adenomatous polyposis, 5 rectal cancer, and 4 hereditary nonpolyposis colorectal cancer. Diverting ileostomies were performed in 40 patients (51.9%) and closed approximately 4 months later. Fourty eight complications were present in 32 patients. There was no perioperative death. There was no difference in perioperative outcome, morbidity or functional status between patients with and without ileostomy. However, in ulcerative colitis patients, anastomosis leakage was more frequent in patients without ileostomy. CONCLUSIONS: Restorative proctocolectomy can be safely performed without diverting ileostomy in most cases of RP. However, diverting ileostomy may reduce anastomosis leakage in patients with ulcerative colitis.
Adenomatous Polyposis Coli ; Colitis, Ulcerative ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Diagnosis ; Humans ; Ileostomy* ; Inflammation ; Postoperative Complications ; Proctocolectomy, Restorative* ; Rectal Neoplasms

Synchronous anal squamous cell carcinoma with colorectal adenocarcinoma is a very rare and interesting disease entity because these neoplasms are essentially different from each other in terms of their anatomical locations, clinical behaviors, histopathological characteristics and treatment. To date, there have been very few case reports regarding the concurrent occurrence of these two distinct neoplasms. Nonetheless, it is recommended that patients with squamous cell carcinoma of the anus and who are older than 50 years should undergo colonoscopy in order to rule out a synchronous colorectal neoplasm. We recently encountered a 72-year-old woman who presented with synchronous squamous cell carcinoma of the anal canal and adenocarcinoma of the rectosigmoid junction. The patient underwent curative surgical resection for the colorectal adenocarcinoma and chemoradiotherapy for the concurrent anal squamous cell carcinoma. We describe here our clinical experience with this unusual case and we also conduct a short review of relevant literature.
Adenocarcinoma ; Aged ; Anal Canal ; Anus Neoplasms ; Carcinoma, Squamous Cell ; Chemoradiotherapy ; Colonic Neoplasms ; Colonoscopy ; Colorectal Neoplasms ; Female ; Humans

Lynch syndrome is the most common inherited colon cancer syndrome. Patients with Lynch syndrome develop a range of cancers including colorectal cancer (CRC) and carry a mutation on one of the mismatched repair (MMR) genes. Although CRC usually occurs after the fourth decade in patients with Lynch syndrome harboring a heterozygous MMR gene mutation, it can occur in children with Lynch syndrome who have a compound heterozygous or homozygous MMR gene mutation. We report a case of CRC in a 13-year-old patient with Lynch syndrome and congenital heart disease. This patient had a heterozygous mutation in MLH1 (an MMR gene), but no compound MMR gene defects, and a K-RAS somatic mutation in the cancer cells.
Adolescent* ; Child ; Colonic Neoplasms ; Colorectal Neoplasms* ; Colorectal Neoplasms, Hereditary Nonpolyposis* ; Female* ; Heart Defects, Congenital ; Humans

Adenomatous Polyposis Coli ; genetics ; pathology ; Colonic Neoplasms ; classification ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; genetics ; DNA Glycosylases ; metabolism ; Humans ; Intestinal Polyps ; pathology ; Lymphatic Metastasis ; Neoplasm Staging ; Neuroendocrine Tumors ; classification ; pathology ; Precancerous Conditions ; pathology ; Rectal Neoplasms ; classification ; genetics ; pathology ; World Health Organization

BACKGROUND: High microsatellite instability (MSI-H) colorectal carcinomas (CRCs) with numerous mutations in the microsatellite sequence are characterized by a right-sided preponderance, frequent peritumoral and intratumoral lymphocytic infiltration, and frequent mucin production. However, no study has correlated anatomic site and type of genetic changes with clinicopathologic changes. METHODS: We analyzed the histopathologic features of 135 MSI-H CRCs and compared them to 140 microsatellite stable (MSS) CRCs. Histopathologic changes in MSI-H were further analyzed according to anatomic sites and genetic changes. RESULTS: MSI-H CRCs showed previously reported clinicopathologic findings; a right-sided preponderance, an increased number of mucinous carcinomas, and peritumoral lymphoid reactions (p<0.001 for each variable). Increased serum CEA levels showed an MSS CRC preponderance (p=0.013). We further analyzed the histologic differences between right- and left-sided MSI-H tumors. We found that MSI-H CRCs on both sides had similar clinicopathologic findings, except for higher tumor stage (p=0.048) and less frequent abnormal CEA levels in left-sided MSI-H tumors (p=0.027). We found that not all clinicopathologic features were different between hereditary nonpolyposis colorectal cancers (HNPCCs) and sporadic MSI-H CRCs. CONCLUSIONS: These findings indicate that MSI-H CRCs of the left colon have similar clinicopathologic characteristics as right-sided MSI-H CRCs. We did not find any significant clinicopathological difference between HNPCCs and sporadic MSI-H CRCs.
Adenocarcinoma, Mucinous ; Calcium Hydroxide ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Microsatellite Instability ; Microsatellite Repeats ; Mucins ; Zinc Oxide

PURPOSE: Sporadic colorectal cancers with high-frequency microsatellite instability (MSI-H) are related to hypermethylation of mismatch repair (MMR) genes and a higher frequency of BRAF mutations than Lynch syndrome. We estimated the feasibility of hereditary colorectal cancer based on hMLH1 methylation and BRAF mutations. METHODS: Between May 2005 and June 2011, we enrolled all 33 analyzed patients with MSI-H cancer (male:female, 23:10; mean age, 65.5 +/- 9.4 years) from a prospectively maintained database that didn't match Bethesda guidelines and who had results of hMLH1 methylation and BRAF mutations. RESULTS: Among the 33 patients, hMLH1 promoter methylation was observed in 36.4% (n = 12), and was not significantly related with clinicopathologic variables, including MLH1 expression. BRAF mutations were observed in 33.3% of the patients (n = 11). Four of 11 and five of 22 patients with MSI-H colon cancers were BRAF mutation (+)/hMLH1 promoter methylation (-) or BRAF mutation (-)/hMLH1 promoter methylation (+). Of the 33 patients, 21.2% were BRAF mutation (+)/hMLH1 promoter methylation (+), indicating sporadic cancers. Seventeen patients (51.5%) were BRAF mutation (-)/hMLH1 promoter methylation (-), and suggested Lynch syndrome. CONCLUSION: Patients with MSI-H colorectal cancers not fulfilling the Bethesda guidelines possibly have hereditary colorectal cancers. Adding tests of hMLH1 promoter methylation and BRAF mutations can be useful to distinguish them from sporadic colorectal cancers.
Colonic Neoplasms ; Colorectal Neoplasms* ; Colorectal Neoplasms, Hereditary Nonpolyposis ; DNA Mismatch Repair ; Humans ; Methylation* ; Microsatellite Instability* ; Prospective Studies

PURPOSE: Sporadic colorectal cancers, with DNA microsatellite instability (MSI), have been characterized by a predilection area of proximal colon, younger age onset, exophytic growth and larger tumor size. MSI colorectal cancers have recently been had a good survival rate. The aim of this study is to determine the MSI status in sporadic colorectal cancers, and compare their clinical and pathological characteristics with those of MSS (Microsatellite Stable) cancers. METHODS: Between March 1995 and December 1997, deep frozen fresh tissue of 107 eligible colorectal cancer patients, who underwent surgical resections, were used for analysis. Hereditary nonpolyposis colorectal cancer, and familial adenomatous polyposis, patients were excluded. All the patients were registered on a colorectal cancer database, and followed up completely with regular visits for a potential recurrence. Genomic DNA was prepared by the SDS-proteinase K and phenol chloroform extraction methods. The DNA was amplified by PCR at five microsatellite loci (BAT26, BAT25, D2S123, D5S346, and D17S250) to evaluate the MSI. The PCR products were separated in 6% polyacrylamide gels, containing 5.6 M urea, followed by autoradiography. The MSI was defined as being over 2 marker positive, and the MSS as 1 marker positive, all marker negatives were classed as MSS. The survival rates were calculated by the Kaplan- Meier methods. RESULTS: MSI was noted at 16/107 (15%), with mean ages for the patients of 51.8 vs. 58.6 years old for MSI and MSS, respectively. For the patients under 40 years old 5 (31.3%) vs. 6 (6.6%) had MSI and MSS, respectively (P<0.01). The cancer was located in the right colon in 12 of each of the MSI and MSS (P<0.01). There were no MSI rectal cancer tumors. The average tumor sizes were 7.6 3.6 cm vs. 5.3 2.2 cm (P<0.01) for MSI and MSS, respectively, but there were no correlations with the frequency of associated polyps, recurrence and distant metastasis between MSI and MSS. The cells were well differentiated (12.5% vs. 17.6%), moderately differentiated (68.8% vs. 76.9%), poorly differentiated (6.2% vs. 3.3%), and mucinous type (12.5% vs. 2.2%), with MSI and MSS, respectively. The overall survival rates were 93.8% vs. 73.8% for MSI and MSS (P=0.07), respectively. CONCLUSIONS: Sporadic colorectal cancer, with DNA microsatellite instability (MSI), was located predominantly in the proximal colon, in the younger age onset, and larger size of tumor. The survival rate of the patients with MSI tumors were good, but with no statistical significance.
Adenomatous Polyposis Coli ; Adult ; Autoradiography ; Chloroform ; Colon ; Colorectal Neoplasms* ; Colorectal Neoplasms, Hereditary Nonpolyposis ; DNA* ; Gels ; Humans ; Microsatellite Instability* ; Microsatellite Repeats* ; Mucins ; Neoplasm Metastasis ; Phenol ; Polymerase Chain Reaction ; Polyps ; Rectal Neoplasms ; Recurrence ; Survival Rate ; Urea