Chang-Ho Jeon

Genetic alterations of APC , K -ras , p53 , MSI, and MAGE in Korean colorectal cancer patients

Background and aimColorectal cancer (CRC) is one of the most rapidly increasing cancers in Korea, but no comprehensive analysis has been performed to speculate the genetic basis of CRC development. We investigated the presence of adenomatous polyposis coli gene (APC), Kirsten-ras (K-ras), p53, microsatellite instability (MSI), and melanoma antigen gene (MAGE) alterations in CRC and correlated the results obtained with clinical data.Materials and methodsWe collected 78 cancer tissues from CRC patients. Genetic analyses were performed on APC, K-ras, p53, and MSI (BAT 25 and BAT 26), and in addition, MAGE expression was tested by reverse transcription polymerase chain reaction. Correlations between genetic markers and clinical factors were analyzed after reviewing medical records.ResultThe positive rates for alterations of APC, K-ras, p53, MSI, and MAGE in 78 tissue samples were 33.3, 29.5, 34.6, 9.0, and 68.4%, respectively. Mutations were frequently detected in codons 1291 and 1450 of APC, in codon 12 of K-ras and in codons 248, 282, and 176 of p53. APC mutations were frequently noted in early-stage cancer, whereas MSI was observed in right-sided and multiple cancers. No associations were found between the presence of alterations in APC, K-ras, p53, MSI, and MAGE.InterpretationIn Koreans, positive rates of alterations in APC and p53 were slightly lower than those of APC and p53 in Caucasians, and the genetic alterations including MAGE expression are involved in 92.1% of CRCs. The lack of multiple mutations and of a relation between mutation rates and clinical stage suggest that genetic alterations might have independent influences on CRC development in Koreans.

Peutz-Jeghers syndrome with germline mutation of STK11

Peutz-Jeghers syndrome (PJS), also known as periorificial lentiginosis, is a rare autosomal dominant inherited disease with an incidence of 1/200,000 live-borns. Mutations in the serine-threonine kinase 11 (STK11) gene are considered the major cause of PJS. The most frequent complication at young age is recurrent intussusception due to multiple hamartomatous polyps, primarily in the small intestine. Although extremely rare, the small bowel should be fully examined to be certain additional intussusceptions are not present. Herein, we report on a case of PJS with germline mutation of STK11 in a 12-year-old young girl who presented as a rare case of two small intestinal intussusceptions and review the literature.

MAGE A1-A6 RT-PCR and MAGE A3 and p16 methylation analysis in induced sputum from patients with lung cancer and non-malignant lung diseases

The melanoma antigen gene (MAGE) A1-A6 RT-PCR system was developed for the detection of lung cancer cells in the sputum. However, we identified MAGE expression in some patients with non-malignant lung diseases. To understand these patterns of MAGE expression, we performed MAGE A3 methylation-specific PCR (MSP) and p16 MSP. We collected 24 biopsy specimens of lung cancer tissue and performed MAGE A1-A6 RT-PCR, MAGE A3 MSP and p16 MSP. RNA and DNA were simultaneously extracted from induced sputum specimens of 133 patients with lung diseases and 30 random sputum specimens of healthy individuals and the 3 molecular analyses were performed. The patients were diagnosed as 65 cases of lung cancer and 68 of benign lung diseases. Positive rates of MAGE A1-A6 RT-PCR, MAGE A3 MSP and p16 MSP were as follows: in lung cancer tissue, 87.5, 58.3 and 70.8%; in the sputum of lung cancer patients, 50.8, 46.2 and 63.1%; benign lung diseases, 10.3, 30.9 and 39.7%; and healthy individuals, 3.3, 6.7 and 3.3%. Of the 40 MAGE-positive cases, 33 were diagnosed with lung cancer and 7 as having benign lung diseases. From the 7 cases of MAGE-positive benign lung diseases, 6 cases showed methylation abnormalities. The MAGE-positive group revealed significantly higher rates of methylation abnormalities. Of the 40 MAGE-positive cases, 39 cases were found to be lung cancer or benign lung diseases with abnormal methylation. Thus, MAGE expression in the sputum suggests the presence of lung cancer cells or pre-cancerous cells.

Prognostic Significance of MAGE in Peritoneal Washes in Gastric Carcinoma Patients Without Peritoneal Metastasis: Results of a 5-year Follow-up Study

Goals The RT-PCR assay of peritoneal washes has been used to predict peritoneal metastasis of gastric carcinoma. We used melanoma associated gene (MAGE) RT-PCR to detect peritoneal metastasis of gastric carcinoma after curative surgery and evaluated its clinical significance. Method Eighty-four peritoneal washes and 23 tumor and normal tissues were obtained from 84 gastric carcinoma patients. MAGE A1-A6 RT-PCR was carried out, and the results were evaluated according to their clinicopathologic characteristics. Five-year follow-up clinical studies were carried out periodically, and overall survival rates were retrospectively investigated using medical records. Results For the paired tumor and normal tissues, MAGE expression rates were 65.2% and 4.3%, respectively. In peritoneal fluids, 11 cases (13.1%) revealed MAGE expression, and higher MAGE expression rates were observed with young age, deeper invasion, and advanced stages of tumor groups. MAGE-positive cases had much higher recurrence rates than MAGE-negative cases (45.5% vs. 9.6%, P<0.002). Among T-stage, N-stage, and MAGE expression; MAGE expression was determined to be the most important prognostic factor for overall survival rate by Cox proportional hazard model analysis. Conclusion MAGE RT-PCR results for peritoneal fluid disclosed significant associations with peritoneal recurrence of gastric carcinoma and proved to be the most important factor for overall survival rate in gastric carcinoma patients who had undergone radical resection.

Clinico-pathologic Parameters for Prediction of Microsatellite Instability in Colorectal Cancer

Purpose Although the incidence of microsatellite instability (MSI) accounts for 10-15% of cases of colorectal cancer, its clinical application for all colorectal cancers has widened. We attempted to identify clinical and pathological parameters that may be helpful in selection of patients with MSI-high (MSI-H). Materials and Methods A total of 120 resected colorectal cancers were enrolled retrospectively for this MSI study. Polymerase chain reaction (PCR) and denaturing high performance liquid chromatography and/or real time PCR methods with five markers and immunohistochemistry (IHC) for MLH1 and MSH2 were performed for analysis of cancer and blood specimens. Clinico-pathologic parameters, including IHC, were investigated in order to determine their usefulness as predictive factors of MSI. Results Among 120 cases of colorectal cancer, MSI was observed in 15 cases (12.5%), including 11 cases of MSI-H and four cases of MSI-low. Patients with MSI were younger, less than 50 years old, had a family history of cancer, Rt. sided colon cancer and/or synchronous multiple colorectal cancer, mucinous histologic type, and serum carcinoembryonic antigen group in the normal range. Results of multivariate analysis showed Bethesda guidelines, Rt. sided and/or synchronous multiple colorectal cancer, and negative expression of IHC for MLH1, which was consistently associated with MSI-H. MSI-H colorectal tumors have met at least one of these three parameters and their sensitivity and specificity were 100% and 72.5%, respectively. Conclusion Bethesda guidelines, tumor location, and negative expression of MLH1 protein are important parameters for selection of patients with colorectal cancers for MSI testing. MSI testing is recommended for patients showing any of these three parameters.

Prognostic Value of Genetic Detection Using CEA and MAGE in Peritoneal Washes With Gastric Carcinoma After Curative Resection: Result of a 3-Year Follow-Up

Abstract Peritoneal metastasis is the most frequent cause of death in patients with gastric cancer. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay of peritoneal washes has been used to predict peritoneal metastasis of gastric carcinoma. We applied carcinoembryonic antigen (CEA) and melanoma-associated gene (MAGE) RT-PCR for the detection of peritoneal metastasis of gastric carcinoma after curative surgery and evaluated its clinical significance. Peritoneal washes were obtained from 117 patients with gastric carcinoma. MAGE A1–A6 and CEA RT-PCR were performed, and the results were evaluated according to their clinicopathologic characteristics. Three-year follow-up clinical studies were periodically performed, and disease-free survival rates were retrospectively investigated using the medical records. Among 117 peritoneal fluids, 11 cases (9.4%) revealed MAGE expression and 38 cases (32.5%) revealed CEA expression. When focusing on recurrence rates, RT-PCR-positive had much higher recurrence rates than RT-PCR-negative cases (32.5% vs 5.2%, P < 0.01). Univariate analysis revealed that depth of invasion, lymph node metastasis, tumor node metastasis (TNM) stage, Lauren classification, and MAGE and CEA expressions were independent prognostic factors for recurrence. In a multivariate analysis, MAGE expression and TNM stage were significantly and independently related to recurrence in patients who underwent curative resection. MAGE expression was determined to be the most important prognostic factor for recurrence (hazard ratio: 12.487, P < 0.01). It is feasible to identify free cancer cells in peritoneal lavage by using a MAGE A1–A6 and CEA RT-PCR. MAGE RT-PCR results disclosed significant associations with peritoneal recurrence and proved to be the most important factor for the recurrence rate in patients with gastric carcinoma who had undergone radical resection.

Gastric Cancer Detection Using Gastric Juice Pepsinogen and Melanoma-Associated Gene RNA

OBJECTIVES To develop a new method for gastric cancer detection with gastric juice using melanoma-associated gene (MAGE) RNA and pepsinogen (PG). METHODS In total, 183 gastric juice and paired serum specimens were obtained from 134 patients with gastric cancer and 49 healthy individuals. The gastric juice specimens were analyzed with MAGE A1 to A6 nested reverse transcription-polymerase chain reaction. The serum and gastric juice PG were measured with a PG I and II immunoassay. RESULTS The gastric juice PG I and PG I/II ratios were more accurate than those of serum. The combination test using the gastric PG I/II ratio and MAGE was the most accurate, with a sensitivity of 77.6% and a specificity of 87.8%. The sensitivity was 78.8% for stage I gastric cancer and not influenced by cancer location or pathologic type. CONCLUSIONS The combination test is potentially an additional tool for gastric cancer detection.

Clinical significance of melanoma-associated antigen A1–6 expression in sputum of patients with squamous cell carcinoma of the larynx and hypopharynx

Several studies have reported the expression of the melanoma‐associated antigen (MAGE) gene in head and neck squamous cell carcinoma (HNSCC). In this study, we evaluated the correlations between MAGE expression in sputum and the clinical features and oncologic outcomes of SCC of the larynx and hypopharynx.

Effects of one directional pneumatic tube system on routine hematology and chemistry parameters; A validation study at a tertiary care hospital

Background The validation of sample stability through pneumatic tube system (PTS) is essential. The objective of this study was to evaluate the effects of PTS transportation on laboratory results. Methods Paired EDTA and SST blood samples were collected from 56 randomly selected patients. Laboratory parameters were compared between PTS group and hand-delivered group. Results No statistical differences were observed for complete blood counts, white blood cell differential parameters, erythrocyte sedimentation rate and most chemistry parameters between PTS and hand-delivered transport procedures. Mean platelet volume results obtained from samples transported through PTS were lower than that obtained from samples transported through hand-delivered method (P = 0.001). The results of aspartate aminotransferase (P = 0.000), lactate dehydrogenase (P = 0.000), and hemolysis index (P = 0.000) from PTS group were higher than that from hand-delivered group. Conclusions All laboratories should validate the stability of the results from samples according to transportation method.