Chong Woo Yoo

Additional value of MR/PET fusion compared with PET/CT in the detection of lymph node metastases in cervical cancer patients

We evaluated the additional diagnostic value of magnetic resonance/positron emission tomography (MR/PET) fusion in the detection of metastatic lymph nodes in cervical cancer patients. Seventy nine patients with FIGO stage IB-IVA cervical cancer who had undergone both magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) before lymphadenectomy were included in this study. Image analysis was first performed with PET/CT images only. A second analysis was then performed with MR/PET fused images that focused on the additional information obtained from the MR images. Lymphadenectomy involved removing all visible lymph nodes in the surgical field. To enable nodal group-specific comparisons, para-aortic and pelvic lymph nodes were divided into seven nodal groups: para-aortic, both common iliac, both external iliac and both internal iliac/obturator areas. Histopathological evaluation of lymph nodes has been the diagnostic standard. The value of the additional information from the MR images was evaluated by means of receiver operating characteristic (ROC) analysis. Fused MR/PET rendered readers to detect six more metastatic lymph node groups. The sensitivity and specificity of PET/CT and fused MR/PET were 44.1%, 93.9% and 54.2%, 92.7% respectively. The ROC analysis demonstrated a higher diagnostic performance of fused MR/PET compared to PET/CT alone for detecting lymph node metastases (p=0.0259). The findings of this study demonstrate the additional diagnostic value of fused MR/PET images compared with PET/CT in the detection of metastatic lymph nodes in patients with uterine cervical cancer.

Insulin-like growth factor binding protein-5 (IGFBP-5) acts as a tumor suppressor by inhibiting angiogenesis

Insulin-like growth factor-binding protein-5 (IGFBP-5) is one of the six members of IGFBP family, important for cell growth control, induction of apoptosis and other IGF-stimulated signaling pathways. In this study, we focused on characterizing the specific function of IGFBP-5 as novel antiangiostatic factor. Overexpression of IGFBP-5 suppressed the tube formation as well as the biological functions of angiostatic activity in vivo. This result is due to the reduced expressions of phosphorylated protein kinase B and phosphorylated endothelial NO synthase, which plays important roles in the regulation of angiogenesis when stimulated by vascular endothelial growth factor. Further, IGFBP-5 expression prevented tumor growth and inhibited tumor vascularity in a xenograft model of human ovarian cancer. These results are the first evidence showing that IGFBP-5 plays a role as tumor suppressor by inhibiting angiogenesis.

Hypoxia-induced up-regulation of apelin is associated with a poor prognosis in oral squamous cell carcinoma patients

Recently, apelin has been shown to be a novel angiogenic factor in various cancers including lung, breast and brain cancer. However, there is limited information regarding the expression and role of apelin in oral cavity cancer. In this study, we determined that apelin expression was localized in the cytoplasm of oral squamous cell carcinoma at various intensities. Strong apelin expression significantly correlated with tumor recurrence and disease-free survival. Using a multivariate analysis, we demonstrated that apelin was an independent prognostic factor for on disease-free survival, age, lymph node metastasis and CA9 expression. Moreover, apelin expression was up-regulated under hypoxic conditions, and exogenous apelin enhanced the proliferation and migration of oral cancer cells. Based on these results, we propose that the presence of hypoxia-induced apelin is a new prognostic factor and potential therapeutic target for oral squamous cell carcinoma.

Protein and lipid MALDI profiles classify breast cancers according to the intrinsic subtype

BackgroundMatrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) has been demonstrated to be useful for molecular profiling of common solid tumors. Using recently developed MALDI matrices for lipid profiling, we evaluated whether direct tissue MALDI MS analysis on proteins and lipids may classify human breast cancer samples according to the intrinsic subtype.MethodsThirty-four pairs of frozen, resected breast cancer and adjacent normal tissue samples were analyzed using histology-directed, MALDI MS analysis. Sinapinic acid and 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument.ResultsProtein and lipid profiles distinguish cancer from adjacent normal tissue samples with the median prediction accuracy of 94.1%. Luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by permutation P values less than 0.01 for 0.632+ bootstrap cross-validated misclassification rates with all classifiers tested. Discriminatory proteins and lipids were useful for classifying tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in random test sets.ConclusionsProtein and lipid profiles accurately distinguish tumor from adjacent normal tissue and classify breast cancers according to the intrinsic subtype.

Pelvic exenteration for recurrent cervical cancer: ten-year experience at National Cancer Center in Korea.

Objective To evaluate survival and morbidity after pelvic exenteration (PE) for the curative management of recurrent cervical cancer. Methods We retrospectively evaluated patients with recurrent cervical cancer who underwent PE from January 2001 to April 2011. Patients were identified from the registry of our institution. The clinical status and demographic information was obtained by reviewing the medical records. Results Sixty-one recurrent cervical cancer patients underwent PE. Patients who received radiotherapy, operation, chemotherapy before PE were 98%, 41%, and 23%, respectively. The total morbidity rate was 44%; 10 (16%) patients had early complications (30 days or less after PE), whereas 22 (36%) patients had late complications. Wound problems were common early complications (7/18), and bowel fistulas were common late complications (9/30). The five-year overall survival and five-year disease-free survival were 56% and 49%, respectively. Median follow-up was 22 months (range, 1.8 to 60 months). Affecting factors for overall survival were resection margin status, pelvic wall and rectal involvement. Conclusion Our overall 5-year survival is encouraging. Although the morbidity rate is still high, PE is a potentially curative opportunity in gynecological malignancies with no other treatment options. The most important factors for overall survival after PE are the resection margin status, pelvic wall involvement and rectal involvement.

The validity of tumour diameter assessed by magnetic resonance imaging and gross specimen with regard to tumour volume in cervical cancer patients

We compared the tumour size measured by magnetic resonance imaging (MRI) with that of gross specimen regarding the virtual tumour volume. Eighty three patients with International Federation of Obstetrics and Gynecology (FIGO) stage Ib to IIa cervical cancer underwent MRI before radical hysterectomy. The largest tumour diameter was determined by both MRI and gross specimen measurement. Tumour volume was calculated by the standard technique of multiplying the sum of the areas by the slice thickness. Paired t-test was used to compare the MRI and gross specimen derived diameters. Pearson correlation coefficient was calculated to evaluate the relationship between the tumour size and volume. The mean diameters of the MRI and gross specimen derived tumour measurements were 3.0 cm (standard deviation, 0.9 cm) and 3.5 cm (standard deviation, 1.2 cm) (p<0.001), respectively. Mean MRI-based tumour volume was 12.5 cm(3) (standard deviation, 10.4 cm(3)). Tumour diameter measured by MRI had a significantly higher correlation with tumour volume measured by MRI (r(p)=0.734) compared with that measured on the gross specimen (r(p)=0.690; Steigers Z test, p=0.019). The tumour diameter measured by MRI was smaller than gross specimen measurement and correlated more closely with tumour volume in patients with cervical cancer. This study illustrates the value of MRI as a tool for tumour size measurement.

Physical status of human papillomavirus integration in cervical cancer is associated with treatment outcome of the patients treated with radiotherapy.

Integration of human papillomavirus (HPV) DNA into the host genome is a critical aetiological event in the progression from normal cervix to intraepithelial neoplasm, and finally to invasive cervical cancer. However, there has been little work on how HPV integration status relates to treatment outcome for cervical carcinomas. In the current study, HPV E2 and E6 gene copy numbers were measured in 111 cervical cancer tissues using real-time QPCR. Integration patterns were divided into four groups: single copy-integrated with episomal components (group 1), single copy-integrated without episomal components (group 2), multicopy tandem repetition-integrated (group 3), and low HPV (group 4) groups. A relapse-predicting model was constructed using multivariable Cox proportional hazards model to classify patients into different risk groups for disease-free survival (DFS). The model was internally validated using bootstrap resampling. Oligonucleotide microarray analysis was performed to evaluate gene expression patterns in relation to the different integration groups. DFS rate was inferior in the order of the patients in group 4, group 2/3, and group 1. Multivariate analysis showed that histologic grade, clinical stage group, and integration pattern were significant prognostic factors for poor DFS. The current prognostic model accurately predicted the risk of relapse, with an area under the receiver operating characteristic curve (AUC) of 0.74 (bootstrap corrected, 0.71). In conclusion, these data suggest that HPV integration pattern is a potent prognostic factor for tailored treatment of cervical cancer.

Practice guidelines for the early detection of cervical cancer in Korea: Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology 2012 edition

The consensus guideline development committee of Korean Society of Gynecologic Oncology was reconvened in March 2012. The committee consisted of 36 experts representing 12 university hospitals and professional organizations. The objective of this committee was to develop standardized guidelines for cervical cancer screening tests for Korean women and to distribute these guidelines to every clinician, eventually improving the quality of medical care. Since the establishment of the consensus guideline development committee, evidence-based guidelines have either been developed de novo considering specific Korean situations or by adaptation of preexisting consensus guidelines from other countries. Recommendations for cervical cancer screening tests, management of atypical squamous and glandular cells, and management of low-grade and high-grade squamous intraepithelial lesions were developed. Additionally, recommendations for human papillomavirus DNA testing and recommendations for adolescent and pregnant women with abnormal cervical screening test results were also included.

Alteration in lipid and protein profiles of ovarian cancer: similarity to breast cancer.

Abstract This study was undertaken to evaluate protein and lipid profiles of ovarian cancer tissue samples. Twenty-three frozen ovarian cancer samples and 6 adjacent normal samples were analyzed using histology-directed, matrix-assisted laser desorption/ionization mass spectrometry. Sinapinic acid and 2, 5-dihydroxybenzoic acid/&agr;-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify protein and lipid profiles respectively, and mass spectra were acquired using a matrix-assisted laser desorption/ionization–time of flight instrument. Protein and lipid profiles classify 11 cancer and 3 adjacent normal samples in 100 random test sets with 92.9% median accuracy. Phosphatidylcholines {32:3} [M + Na]+ (m/z = 750.66), {34:1} [M + K]+ (m/z = 798.60), and {36:2} [M + K]+ (m/z = 824.56) were found to be increased in ovarian cancer. Interestingly, breast cancer–associated changes in lipid and protein profiles were also found in ovarian cancer. Thus, protein and lipid profiles accurately distinguish ovarian cancer from adjacent normal tissue samples. Common cancer-associated alterations in lipid and protein profiles were identified between ovarian and breast cancers.

Lipid profiles for intrahepatic cholangiocarcinoma identified using matrix-assisted laser desorption/ionization mass spectrometry

BACKGROUND We evaluated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis of lipids may distinguish intrahepatic cholangiocarcinomas from adjacent normal tissue and from other adenocarcinomas that frequently metastasize to liver. METHODS Four pairs of frozen surgical specimens of cholangiocarcinomas and adjacent normal tissue were analyzed using histology-directed, MALDI MS analysis. 2,5-dihydroxybenzoic acid / α-cyano-4-hydroxycinnamic acid were manually deposited on tumor-rich areas, and mass spectra were acquired using a MALDI-time of flight instrument. RESULTS Cholangiocarcinomas and adjacent normal tissue samples demonstrated different lipid profiles, as evidenced by permutation P value<0.05 for the cross-validated misclassification rate. Cancer-associated lipid alteration was similar between cholangiocarcinomas and pancreatic cancers, but not between cholangiocarcinomas and colorectal cancers. Baseline lipid profiles were different between cholangiocarcinoma and colorectal cancers. CONCLUSIONS MALDI MS analysis of lipid distinguishes cancerous epithelium of cholangiocarcinoma from adjacent normal tissue, and between cholangiocarcinomas and colorectal cancers.