PURPOSE: The Korean Hereditary Tumor Registry, the first and one of the largest registries of hereditary tumors in Korea, has registered about 500 families with hereditary cancer syndromes. This study evaluates the temporal changes in clinicopathologic features and surgical patterns of Lynch syndrome (LS) patients. MATERIALS AND METHODS: Data on 182 unrelated LS patients were collected retrospectively. The patients were divided into the period 1 group (registered in 1990-2004) and 2 (registered in 2005-2014). The clinical characteristics of the two groups were compared to identify changes over time. RESULTS: The period 1 group included 76 patients; the period 2 group, 106 patients. The mean ages at diagnosis were 45.1 years (range, 13 to 85 years) for group 1 and 49.7 years (range, 20 to 84 years) for group 2 (p=0.015). The TNM stage at diagnosis did not differ significantly-period 1 group: stage 0-I (n=18, 23.7%), II (n=37, 48.7%), III (n=19, 25.0%), and IV (n=2, 2.6%); period 2 group: stage 0-I (n=30, 28.3%), II (n=35, 33.0%), III (n=37, 34.9%), and IV (n=4, 3.8%). Extended resection was more frequently performed (55/76, 72.4%) in the period 1 group than period 2 (49/106, 46.2%) (p=0.001). CONCLUSION: Colorectal cancer in patients with LS registered at the Korean Hereditary Tumor Registry is still diagnosed at an advanced stage, more than two decades after registry's establishment. Segmental resection was more frequently performed in the past decade. A prompt nationwide effort to raise public awareness of hereditary colorectal cancer and to support hereditary cancer registries is required in Korea.
Colorectal Neoplasms ; Colorectal Neoplasms, Hereditary Nonpolyposis* ; Diagnosis ; Humans ; Korea ; Neoplastic Syndromes, Hereditary ; Registries ; Retrospective Studies

Hereditary nonpolyposis colorectal cancer(HNPCC) is an autosomal dominantly inherited disease associated with a marked increase in cancer susceptibility, especially cancer of the colorectum. The frequency of HNPCC in the general population is yet to be determined, but HNPCC may account for as much as 2% to 5% of colorectal cancer, Colorectal cancer in HNPCC differs from sporadic colorectal cancer by an early age of cancer onset, proximal predominance of colorectal cancer, an excess of synchronous and metachronous colorectal cancer, and excess extra-colonic cancers. We have found 5 HNPCC families since 1992 when we reported first HNPCC family (KHU-Hl) In order to register the patients of HNPCC and to review the clinicopathologic feature and appropriate management, we have analysed 5 HNPCC families. Five HNPCC families included 16 colorectal cancer patients(14 males and 2 females). The average age of first diagnosis was 39. Among 16 patients, 8 patient were operated at the KyungHee University hospital and their operative and pathologic records were available. Two synchronous and seven metachronous cancers were founded, so that eight patients had 15 colorectal cancer lesions. Ten cancers were located proximal to splenic flexure and five were distal. Partial resection of colon was performed in seven cases except one when the first diagnosis was made and recurrence was founded in 5 patients. Recurrence was treated by total colectomy in 3 cases and subtotal colectomy in two. In conclusion, we re-confirmed that HNPCC patient should be treated by no less than a subtotal colectomy because of high multiplicity and high recurrence rate of partial resection.
Colectomy ; Colon ; Colon, Transverse ; Colorectal Neoplasms ; Colorectal Neoplasms, Hereditary Nonpolyposis* ; Diagnosis ; Humans ; Male ; Recurrence

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited disease associated with germ-line mutations in mismatch repair genes and microsatellite instability. This article reviews the molecular biology and clinical pathology of HNPCC.
Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; genetics ; pathology ; DNA Mismatch Repair ; Humans ; Microsatellite Instability

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

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary colorectal cancer syndrome and accounts for about 5% of colorectal cancer. It is inherited as autosomal dominant type and is caused by germline mutations in mismatch repair genes such as MLH1, MSH2, MSH6, and PMS2. Patients with HNPCC are characterized by a high level of microsatellite instability. They commonly develop colorectal cancer at young age and increase risk of extra-colic malignancies, especially endometrial cancer. They also show better oncologic outcomes compared to sporadic colorectal cancer. Several tools are used in diagnosis of HNPCC, including history taking, microsatellite instability test, immunohistochemistry for mismatch repair protein, and gene test. Affected patients and their families should get genetic counseling and regular surveillance for cancers, which can improve their survival rate.
Colorectal Neoplasms ; Colorectal Neoplasms, Hereditary Nonpolyposis* ; Diagnosis ; DNA Mismatch Repair ; Endometrial Neoplasms ; Female ; Genetic Counseling ; Genetic Testing ; Germ-Line Mutation ; Humans ; Immunohistochemistry ; Microsatellite Instability ; Survival Rate

BACKGROUND: Although the incidence of colorectal cancer in young adults is low, they seem to show advanced tumors with a poor prognosis at their initial presentation due to diagnostic delay. We evaluated colorectal cancer in young patients with respect to clinical characteristics and prognosis. METHODS: Twelve hundred and seventy-three colorectal cancer patients were evaluated retrospectively. Familial adenomatous polyposis and ulcerative colitis related cases were excluded. We grouped these patients into younger (40 years old) and older (>40 years old) patients. These two groups were compared with respect to sex, tumor location, duration of symptoms and signs, patterns of DNA ploidy, histological differentiations, TNM stage, survival rate, and familial tendency of colorectal cancer. RESULTS: One hundred forty-nine patients (11.7%) were 40 years old or younger. There was no significant difference between the two groups with respect to sex, tumor location, patterns of DNA ploidy, and 5-year survival rate. Histological patterns revealed a higher incidence of mucinous and signet-ring cell tumors in the younger group than in the older group (12.7% vs. 2.7% and 4.0% vs. 0.7%, p<0.05). The duration of the symptoms was shorter in the younger group, being less than 3 months in 56.3% of the younger group and 36.3% of the older group. Colorectal cancer in the younger group seemed to present more advanced lesions, especially those in stage III. Familial clustering of cancers(younger group, 25.5%; older group, 9.3%) and hereditary nonpolyposis colorectal cancer(younger group, 7.4%; older group, 0.7%) were more prevalent in the younger group. CONCLUSION:For colorectal cancer in younger patients with histological shortcomings and familial clustering, every effort is needed to make an earlier diagnosis.
Adenomatous Polyposis Coli ; Adult* ; Colitis, Ulcerative ; Colorectal Neoplasms* ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Diagnosis ; DNA ; Humans ; Incidence ; Mucins ; Ploidies ; Prognosis* ; Retrospective Studies ; Survival Rate ; Young Adult

Hereditary nonpolyposis colon cancer(HNPCC) accounts for 1~6% of colorectal cancer. Mutations in the DNA mismatch repair genes(hMSH2, hMLH1 and hPMS1, hPMS2 and hMSH6) are responsible for HNPCC. To evaluate the clinical characteristics of Korean HNPCC patients, analysis were performed on the 176 patients from 40 HNPCC families registered in the Korean Hereditary Tumor Registry. All the families in this study fulfilled the ICG-HNPCC criteria. The control group consisted of 1,204 patients of nonhereditary colorectal cancer operated at SNUH between 1991 and 1995. The mean age of patients at diagnosis was significantly lower than the control group (44.5 vs 56.1 years old). Thirty three percent of cancers were located proximal to splenic flexure compared to 23% in control group. Among the 71 patients whose pathological reports were available, 14 patients(20%) had synchronous colorectal cancer compared to 4% in control. Also 15 patients(21%) had synchronous adenomatous polyp and 3 patients had both the synchronous cancer and polyp. Thus, overall 26 patients (36%) had multiple colorectal cancer including polyp. The cancers in HNPCC patients were detected at significantly earlier stage than control(67% of HNPCC patients were Dukes A or B compared to 48% in control). Statis tically significant difference was not observed in tumor differentiation between HNPCC and control group. In terms of treatment, 64% of patients received an extensive surgery over subtotal colectomy between 1995~1997 compared to 31% in the period of 1991~1994. In this series, we confirmed that Korean HNPCC patients have similar characteristics with western countries in that an early age of onset, a proclivity for the proximal colon and excess of synchronous colorectal cancers. However, relatively low incidence of proximal colonic involvement and low rate of mucinous or poorly differentiated carcinoma differed from the reports from the western countries.
Adenomatous Polyps ; Age of Onset ; Colectomy ; Colon ; Colon, Transverse ; Colorectal Neoplasms ; Colorectal Neoplasms, Hereditary Nonpolyposis* ; Diagnosis ; DNA Mismatch Repair ; Humans ; Incidence ; Mucins ; Polyps

Hereditary syndromes cause approximately 5 to 15% of overall colorectal cancer (CRC) cases. Hereditary CRC is conventionally divided into two major categories: hereditary non-polyposis colorectal cancer (HNPCC) and those related to polyposis syndromes including familial adenomatous polyposis (FAP), Peutz-Jegher syndrome (PJS), and juvenile polyposis (JP). The screening for the cancer and methods of treatment applied to patients with hereditary CRC are quite different from those applied to the general population. The genes responsible for these syndromes has recently identified, as a result, genetic testing has become the most important determining factor in clinical decisions. Germ-line mutation of the APC gene induces FAP, an autosomal dominant disorder, characterized by the development of hundreds to thousands of colonic adenomas. CRC appears in almost all affected individuals by the time they are 50 years of age. An affected individual should undergo colectomy by his/her late teens. Furthermore, according to the findings of genetic testing, at-risk family members also need endoscopic surveillance and surgery. Recently, a mutation on the MYH gene is increasingly being investigated in patients with multiple polyps, and autosomal recessive MYH polyposis is considered to be a new category of polyposis. More common than FAP, HNPCC is caused by germ-line mutations in DNA mismatch repair genes, mainly MLH1 and MSH2. Although there is no polyposis, polyps seem to be more villous and dysplastic and appear to grow rapidly into CRCs. The aggregate lifetime risk of CRC is about 80% for mutation carriers. The risk for other types of cancer, such as endometrial, ovarian, small bowel, and transitional cell cancer, is also increased. The Amsterdam criteria and Bethesda guidelines are the best-known tools for diagnosis and genetic testing, and colectomy followed by endoscopic follow-up is the standard treatment. PJS and JP are reported to be characterized by hamartomatous polyps throughout the GI tract and germ-line mutations in the STK11 gene (PJS) and the DPC4/BMPR1A gene (JP).
Adenomatous Polyposis Coli/*genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis/*genetics ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Intestinal Polyposis/diagnosis/*genetics ; Peutz-Jeghers Syndrome/diagnosis/*genetics

We have recently experienced an endometrial cancer 12 years after the diagnosis of colon cancer with Lynch syndrome. A 49-year-old Korean woman had a family history of colon cancer. Her mother had colon cancer at 56-year-old, and her brother had colon cancer at 48 years old. The patient received surgery for endometrial cancer at the same hospital 12 years after being treated for colon cancer. Immunohistochemistry showed that her endometrial tissue stained negative for MSH2. A microsatellite instability test was performed and showed the presence of instability high microsatellite instability. An hMLH2 gene mutation was detected at codon 629 codon of exon 12, in which a glutamine was replaced with an arginine (1886A>G [p.Gln629Arg]). To our knowledge, this is the first case of metachronous cancer in a Lynch syndrome family in Korea with a gap of more than ten years between cancer diagnoses.
Arginine ; Colon* ; Colonic Neoplasms* ; Colorectal Neoplasms, Hereditary Nonpolyposis* ; Diagnosis ; Endometrial Neoplasms* ; Female ; Glutamine ; Humans ; Immunohistochemistry ; Korea ; Microsatellite Instability ; Middle Aged ; Mothers ; Siblings

OBJECTIVE: To evaluate the importance of Lynch syndrome associated risk screening in the patients aged less than 50 years affected from endometrial cancer. METHODS: From 2007 to 2014, 41 patients affected from endometrial cancer and aged less than 50 years underwent surgery at the Complex Operative Unit of Gynecology and Obstetrics, Cannizzaro Hospital of Catania, Italy. They were selected to undergo mismatch repair gene mutation analysis using immunohistochemistry (IHC; four markers: MLH1, MSH2, MSH6, PMS2) and microsatellite instability (MSI) test. For samples that resulted negative to IHC (abnormal finding), MSI test was performed to further study the suspected mutation. Samples were classified as MSI-high (MSI-H) if more than one marker was identified as unstable; MSI-low (MSI-L) if only one marker was identified as unstable; or MSI-stable (MSI-S) if no marker was identified as unstable. Samples were subdivided into two groups: MSI-H/L and MSI-S. Statistical analysis was performed to assess differences regarding survival, tumor staging, grading, and invasion of lymphovascular space between these two groups. RESULTS: IHC analysis showed that in 46% (19/41) of samples there was negative outcome. Forty-two percent (8/19) of these negative samples were unstable (either low or high). Of eight patients showing MSI, 75% were MSI-L, while 25% were MSI-H. Differences in survival, stage, grade, lymphovascular space invasion and Amsterdam criteria adherence were not statistically significant due to the small size of the cohort. CONCLUSION: IHC and MSI test results of our cohort lead us to assess the relevance of performing Lynch syndrome genetic screening in endometrial cancer patients aged less than 50 years at the time of diagnosis.
Cohort Studies ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Diagnosis ; DNA Mismatch Repair ; Endometrial Neoplasms* ; Female ; Genetic Testing* ; Gynecology ; Humans ; Immunohistochemistry ; Italy ; Mass Screening ; Microsatellite Instability ; Neoplasm Staging ; Obstetrics