Bo Sung Yoon

Analysis of chromosomal changes in serous ovarian carcinoma using high-resolution array comparative genomic hybridization: Potential predictive markers of chemoresistant disease

The mechanism of drug resistance in cancer is multifactorial, and the accumulation of multiple genetic changes may lead to drug‐resistant phenotypes. This study sought to determine characteristic genetic changes in chemoresistant serous ovarian carcinomas using high‐resolution array comparative genomic hybridization (aCGH), and identified genomic aberrations that could be used as predictive markers of chemoresistant disease. Seventeen primary ovarian tumors from optimally debulked stage IIIc serous ovarian carcinoma patients were analyzed using aCGH. Ten patients had chemoresistant disease (progression within 12 months of initial chemotherapy), whereas seven patients had chemosensitive disease (no recurrence for more than 36 months). Receiver operating characteristics curve analysis was used to select chromosomal aberrations that could help distinguish chemoresistant disease from chemosensitive disease. In 17 tumors, frequent increases in DNA copy number were seen on 1p36.33, 3q26.2, 8q24.3, 10q26.3, 12p11.21, 20q13.33, and 21q22.3, and frequent losses were observed on 4p12, 5q13.2, 7q11.21, 8p23.1, 14q32.33, Xq13.3, and Xq21.31. The gains on 5p15.33 and 14q11.2, and losses on 4q34.2, 4q35.2, 5q15, 8p21.1, 8p21.2, 11p15.5, 13q14.13, 13q14.2, 13q32.1, 13q34, 16q22.2, 17p11.2, 17p12, and 22q12.3 were more frequent in chemoresistant disease. The losses on 13q32.1 and 8p21.1 had the largest areas under the curve (AUC 0.90 and 0.85, respectively). The most reliable combination of chromosomal aberrations for detecting chemoresistant disease was the loss on 13q32.1 and 8p21.1 (AUC 0.950). Our findings suggest that these chromosomal aberrations are potential predictive markers of chemoresistant disease in patients with serous ovarian carcinomas.

Prognostic significance of paired epithelial cell adhesion molecule and E-cadherin in ovarian serous carcinoma

This study was designed to investigate the prognostic significance of the expression of paired epithelial cell adhesion molecule and E-cadherin in ovarian serous carcinoma. The expression of epithelial cell adhesion molecule and E-cadherin was examined immunohistochemically on a tissue microarray of formalin-fixed paraffin-embedded tissue specimens from 72 consecutive patients. The overexpression of epithelial cell adhesion molecule was correlated with poor survival (P = .036). In contrast, the reduced expression of E-cadherin was correlated with poor survival (P = .034). When patients were subclassified into 4 groups according to positivity and negativity of epithelial cell adhesion molecule and E-cadherin expression, the epithelial cell adhesion molecule-positive E-cadherin-negative group showed the worst survival rate (P = .002, compared with the epithelial cell adhesion molecule-negative E-cadherin-positive group). These data suggest that the overexpression of epithelial cell adhesion molecule and reduced expression of E-cadherin in combination is more significant than a single marker for predicting poor survival.

Clinical Significance of Microsatellite Instability in Sporadic Epithelial Ovarian Tumors

Purpose We evaluated the expression of microsatellite instability (MSI) in sporadic ovarian tumors using 5 standard and 9 new MSI markers to determine the clinical significance of MSI in sporadic epithelial ovarian tumors. Materials and Methods MSI was examined in 21 borderline and 25 malignant ovarian tumors. Polymerase chain reaction (PCR) was performed using the 5 markers recommended by the National Cancer Institute (NCI) for colon cancer and 9 additional markers. MSI was determined using fractional analysis by mixing the PCR products and size markers. Results Using the 5 conventional MSI markers, MSI was found in 4 of 46 (8.6%) ovarian tumors, including 2 of 21 (9.5%) borderline ovarian tumors and 2 of 25 (8%) malignant ovarian tumors. Using the 9 additional MSI markers, MSI was observed in 7 of 46 (15.2%) ovarian tumors, including 3 of 21 (14.3%) borderline ovarian tumors and 4 of 25 (16%) malignant ovarian tumors. There was no statistically significant difference between MSI and clinicopathological factors, including histology and stage, although there was a trend toward an increased incidence of MSI in the serous type. Conclusion MSI was infrequent in ovarian tumors, including both borderline and malignant tumors. MSI was found to be uncommon in sporadic ovarian tumors, even by using additional MSI markers. The clinical significance of MSI is not strong in patients with sporadic ovarian tumors.

Clinical Usefulness of Cervicogram as a Primary Screening Test for Cervical Neoplasia

The purpose of this study is to evaluate the clinical usefulness of the cervicogram as a primary screening test for cervical neoplasia. A total of 294 women who had undergone a cervicogram and a Pap test between January and July 2003, were selected. The diagnostic accuracy of the Pap test, cervicogram, and the Pap test combined with a cervicogram were compared with the histopathologic diagnosis. Among 294 women, the Pap test was negative in 130 cases and positive in 164 cases. Among patients with positive Pap test, cervicogram were negative in 101 cases (61.6%) and positive in 63 cases (38.4%). The diagnostic accuracy between cervicogram with positive Pap test and histology was as follows; sensitivity 44.9%, specificity 78.3%, positive predictive value 84.1%, negative predictive value 32.7%, false positive rate 15.9%, and false negative rate 67.3%. Although the adjunctive use of cervicogram with the Pap test in the initial screening of cervical neoplasia showed a higher specificity and higher positive predictive value compared to the Pap test alone, consideration in terms of lower sensitivity, lower positive predictive value, higher false positive rate and cost-effectiveness should be given in lieu of clinically applying cervicogram with the pap test as an initial screening test.