Insun Kim

Peutz-Jeghers syndrome with multiple genital tract tumors and breast cancer: A case report with a review of literatures

We report here on the multiple genital tract neoplasms in a 41-yr-old Korean woman with Peutz-Jeghers Syndrome (PJS). The patient presented with lower abdominal pain. Her previous medical history was PJS and breast cancer. Pelvic ultrasound showed a multilocular cyst at the right adnexal region, diagnosed as bilateral ovarian mucinous borderline tumors. An ovarian sex cord tumor with annular tubules was incidentally diagnosed together with a minimal deviation adenocarcinoma of the uterine cervix and mucinous metaplasia of both the Fallopian tubal mucosa and the endometrium. Although the cases of multiple genital tract tumors with PJS has rarely been reported, the present case appears to be the first in Korea in which the PJS syndrome was complicated by multiple genital tract tumors and infiltrating carcinoma of the breast. The clinical significance of the multiple genital tract tumors and breast cancer associated with PJS is reviewed.

Epstein-Barr Virus and p16INK4A Methylation in Squamous Cell Carcinoma and Precancerous Lesions of the Cervix Uteri

Methylation of p16 is an important mechanism in cervical carcinogenesis. However, the relationship between cervical squamous cell carcinoma (SCC) and Epstein-Barr virus (EBV) remains controversial. Here, we explored whether EBV infection and/or p16 gene inactivation would play any role in cervical carcinogenesis. Eighty-two specimens included 41 invasive SCCs, 30 cervical intraepithelial neoplasm (CIN; CIN 1, 11 cases, CIN II, 3 cases, CIN III 16 cases) and 11 nonneoplastic cervices. EBV was detected by polymerase chain reaction (PCR) for EBNA-1 and in situ hybridization for EBER-1. The p16 methylation-status and the expression of p16 protein were studied by methylation-specific PCR and immunohistochemistry, respectively. The materials were divided into four groups: 1) nonneoplastic cervices, 2) CIN I, 3) CIN II-III and 4) invasive SCCs. p16 methylation and p16 immunoexpressions increased in CIN and invasive SCCs than nonneoplastic tissue. p16-methylation and p16-immunoreactivities were higher in the EBV-positive group (p=0.009, p<0.001) than in the EBV-negative group. EBV was detected more frequently in CIN and SCCs than nonneoplastic cervices. In conclusion, a correlation between p16 methylation, p16 immunoreactivity and the detection of EBV strongly suggested that the cooperation of EBV and p16 gene may play a synergic effect on cell cycle deregulation.

Prognostic significance of histological grade in clear-cell carcinoma of the ovary: a retrospective study of Korean Gynecologic Oncology Group

BACKGROUND This study was to investigate the prognostic significance of clinicopathologic characteristics in patients with clear-cell carcinoma (CCC) of the ovary. MATERIALS AND METHODS Two hundred and one patients with CCC of the ovary were registered in the Korean Gynecologic Oncology Group. The Korean Gynecologic Pathology Study Group reviewed the pathological slides centrally, using a universal grading system. The prognostic significances of clinicopathologic factors were evaluated by multivariate analysis. RESULTS Most of the patients were diagnosed at an early stage (stage I, 61.3%), and the overall 5-year survival rate was 57%. Early-stage disease showed a favorable prognosis, but advanced diseases showed poor prognosis. Stage of disease was the only significant prognostic factor on multivariate analysis (P < 0.001). However, universal grade and residual tumor also showed prognostic significance on the forward stepwise likelihood ratio test. There was no survival difference observed between patients treated with paclitaxel-based and those treated with platinum-based combination chemotherapy. CONCLUSIONS The stage, residual tumor, and universal grade were significant prognostic factors in patients with CCC of the ovary. The universal grading system is applicable in determining prognosis of CCC of the ovary. Further clinical trials for optimal chemotherapy are in need.

The Usefulness of Cytokeratin Immunohistochemistry in Detection of Lymph Node Micrometastasis in Neck Dissection Specimens

OBJECTIVE: Our study was designed to find out the rate and the characteristics of micrometastasis in cervical lymph nodes using immunohistochemical staining. STUDY DESIGN AND SETTING: From 69 patients, 1710 lymph nodes negative for metastasis on hematoxylin-eosin stain, were examined. Immunohisto-chemical stain was performed using pan-cytokeratin AE1/AE3 antibody. RESULTS: In 13 cases, occult lymph node metastasis was detected by immunohistochemical method. On retrospective review of the hematoxylin-eosin stain by the pathologist, lymph node metastasis was detected in 4 of 13 patients. CONCLUSIONS: Because the immunohistochemical method enhanced the detection rate of occult micrometastasis in cervical lymph nodes of head and neck squamous cell carcinoma patients, it may be recommended for routine diagnostic use in patient with negative for a lymph node metastasis on routine hematoxylin-eosin stain.

Retrospective multicenter study of a clinicopathologic analysis of pseudomyxoma peritonei associated with ovarian tumors (KGOG 3005)

The purpose of this study is to assess clinicopathologic features of pseudomyxoma peritonei (PMP) that has ovarian pathology and its relationship with the prognosis. From 1995 to 2004, the clinical records and follow-up data of 35 patients with PMP, which had primarily originated from the ovary, were collected from 11 institutes of gynecologic oncology in Korea and retrospectively analyzed. All patients had ovarian lesion histologically confirmed with PMP. The mean age at diagnosis was 53.7 years (range: 16–82 years). There were 25 (71.4%) patients with disseminated peritoneal adenomucinosis, 5 (14.3%) with peritoneal mucinous carcinomatosis with intermediate group, and 5 (14.3%) with peritoneal mucinous carcinomatosis. The clinical stages at diagnosis were IA in 2 patients, IIIB in 4, IIIC in 23, IV in 1, and unknown in 5. In preoperative tumor markers, the positive rates were 72% (CA125), 47.4% (CA19-9), and 84.6% (CEA). Thirty-four patients underwent surgical staging or cytoreduction, and then 27 patients (77%) received adjuvant chemotherapy that was given to patients in a nonuniform fashion. The 5-year survival for 35 patients was 87%. Survival rate was significantly lower in patients >50 years of age (P= 0.002). Our data showed that age of the patient is the only significant prognostic factor in PMP that has ovarian lesion.

The expression of epidermal growth factor receptor, vascular endothelial growth factor, matrix metalloproteinase-2, and cyclooxygenase-2 in relation to human papilloma viral load and persistence of human papillomavirus after conization with negative margins

The aim of this study was to investigate the correlations between human papillomavirus (HPV) load and vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), matrix metalloproteinase-2 (MMP-2), and cyclooxygenase-2 (COX-2), and to identify biomarkers that may predict high-risk HPV clearance or persistence after conization with negative margins. The following samples were analyzed: 77 paraffin-embedded specimens from patients with cervical intraepithelial neoplasia (CIN), including 27 CIN 2 conization specimens and 50 CIN 3 conization specimens. Immunohistochemical analysis was performed with antibodies to VEGF, EGFR, MMP-2, and COX-2. Hybrid capture II testing was used to detect HPV DNA. VEGF expression was significantly associated with HPV load (ρ = 0.27186, P= 0.0191), while COX-2 expression was significantly and inversely associated with HPV load (ρ =−0.34309, P= 0.0028). In univariate analysis, HPV load (P= 0.0112) and VEGF expression (P= 0.0274) were significantly associated with high-risk HPV clearance or persistence after conization with negative margins. In multiple regression analysis, high viral load (relative light unit/positive control > 500) and positive VEGF expression were significantly associated with high-risk HPV persistence after conization with negative margins (odds ratio [OR]: 9.915, CI: 1.891–51.994; OR: 6.661, CI: 1.208–36.722, respectively). In conclusion, VEGF expression is related to HPV load, while COX-2 expression is inversely related to HPV load, and immunohistochemical analysis of VEGF expression and HPV viral load are a significant and an independent prognostic indicator of high-risk HPV persistence after conization with negative margins.

A Hybrid Carcinoma of Epithelial-Myoepithelial Carcinoma and Adenoid Cystic Carcinoma in Maxillary Sinus

Hybrid carcinoma of the salivary gland is a very rare entity that has been described only in the parotid and palate. The occurrence of a hybrid carcinoma of maxillary sinus has not been reported. The diagnosis of hybrid carcinoma is important particularly when the components of tumor have different biologic behaviors. Diagnosis and treatment require a high index of suspicion, especially when the tumor is an epithelial-myoepithelial carcinoma, pathological effort to look for a more aggressive accompanying tumor, and proper oncologic treatment. We describe a case of 26-yr-old woman with a hybrid carcinoma composed of epithelial-myoepithelial carcinoma with an adenoid cystic carcinoma component (cribriform pattern) in the right maxillary sinus with a brief review of the relevant literature.

Borderline-like mucinous tumor arising in mature cystic teratoma of the ovary associated with pseudomyxoma peritonei.

SUMMARY Pseudomyxoma peritonei (PMP) is now considered to originate from appendiceal mucinous neoplasms in almost all cases. However, a mucinous neoplasm arising in a mature cystic teratoma is rarely responsible for PMP. We herein report 2 cases of PMP associated with borderline mucinous tumors arising in mature cystic teratoma. Both ovarian borderline mucinous tumors were morphologically and immunohistochemically similar to the secondary tumors from appendiceal origin, and PMP was histologically similar to peritoneal adenomucinosis.

BCL6 Gene Mutations in Transitional Cell Carcinomas

The B-cell lymphoma-6 (BCL6) gene was initially identified at a translocation site observed frequently in diffuse large B-cell lymphomas. In the present study, BCL6 mutations at the 5′ non-coding region in 47 cases of transitional call carcinoma (TCC) were analysed using polymerase chain reaction–single-strand conformation polymorphism. The results were compared with data obtained previously by immunohistochemical staining for the BCL6 protein. Overall, BCL6 mutations were observed in 44.7% of cases. Mutation of the 5′ non-coding region was not correlated with histological grade of the tumour; however, the better the histological grade, the greater the mutation rate of the E1.12 fragment. The BCL6 mutation occurred independently of over-expression of the protein. The BCL6 gene mutation and the protein expression were detectable in a large proportion of TCCs. BCL6 protein over-expression as well as BCL6 gene mutation of the E1.12 fragment may play an important role in the morphological differentiation of TCC.

An exactly solvable self-avoiding walks model

A self-avoiding walks model is studied in which the walker is, in addition to the usual self-avoiding condition, restricted not to make any turn which will put the walker in a direction rotated more than Phi max from any of the directions previously taken. Here, Phi max( Phi R where Phi R=2 pi - (the smallest exterior angle of the unit cell of the lattice under consideration). The generating function for the square lattice is obtained, and various properties such as the number of N-step walks, the total number of steps to given directions and the mean-square end-to-end distance are evaluated analytically. The model exhibits characteristics reminiscent of one-dimensional self-avoiding walks in all directions, while retaining the anisotropic effect of the direction of the first step.