Prevalence and Genotype Distribution of Cervical Human Papillomavirus DNA in Korean Women: A Multicenter Study

Background: DNA prevalence and type distribution of human papillomavirus (HPV) varies geographically. We investigated HPV prevalence and type distribution in Korean women using the MyHPV DNA chip testing. Methods: A total of 2,368 women from five regions of the country underwent Pap smear examination and MyHPV chip testing. Results: Overall HPV positivity was 15.8% and 78.4% in women with normal and abnormal cytology, respectively. High-risk HPV infection was strongly correlated with cytological atypia. In women with abnormal cytology, the five most common HPV types were 16, 58, 18, 52, and 56/53, and HPV16 was significantly the most common type in most geographical regions. After HPV16, HPV58, and 52 were the next most frequently detected types. Women with normal cytology, in contrast, showed heterogeneity in HPV type distribution. High-grade intraepithelial lesions infected with HPV16, 18, 31 or 45 are more likely to progress to carcinoma. Conclusions: The HPV chip test can provide useful data regarding HPV positivity and type. The most common HPV type in Korean women with abnormal cytology is HPV16, with HPV58 and 52 being frequently present. Our data may have important implications for vaccination programs and the development of cervical screening.

A Case of Nonspecific Interstitial Pneumonia in a Patient with Ulcerative Colitis / 결핵및호흡기질환

Pulmonary complications of ulcerative colitis are relatively uncommon and may present as a variety of disorders. Ulcerative colitis-related interstitial lung disease is extremely rare. There are a few case reports of nonspecific interstitial pneumonia in ulcerative colitis worldwide but none in Korea. We report a patient with ulcerative colitis related biopsy-proven nonspecific interstitial pneumonia, who responded to prednisolone (1 mg/kg) and mesalazine therapy

Methodologic Evaluation of EGFR Expression in Colorectal Cancer

PURPOSE: The epidermal growth factor receptor (EGFR) is a one of the transmembrane receptor proteins that play an important role in initiating tumor cell signaling and growth and is regarded as a promising target for cancer therapy. The EGFR expression rate has been reported to vary according to the detection method. The aims of this study were to evaluate the EGFR expression rate of a colorectal carcinoma by using immunohistochemical staining (IHC) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and to analyze the correlation between these methods. METHODS: EGFR expression was investigated in tissue sections from 33 patients with a colorectal adenocarcinoma by using IHC and semiquantitative RT-PCR. IHC was performed with antibodies in a 1:40 dilution and a 1:80 dilution. The results of the three detection methods were compared with one another. RESULTS: The mean age of the patients was 61.9+/-12.2 years, and the male-to-female ratio was 1.2:1. The EGFR expression rates were 93.9% (31/33) in IHC with a 1:40 dilution, 87.9% (29/33) in IHC with a 1:80 dilution, and 66.7% (22/33) in RT-PCR. The result of IHC with a 1:40 dilution significantly correlated with the result of IHC with a 1:80 dilution (Pearson correlation 0.684, P<0.01). There was no correlation between semiquantitative RT-PCR and IHC (1:40 dilution, 1:80 dilution). CONCLUSIONS: The EGFR expression obtained by using IHC was consistent with different antibody dilutions. The expression rate obtained by using RT-PCR was significantly lower than that obtained by using IHC, and there was no statistical correlation between the expressions of EGFR obtained by using RT-PCR and IHC. A standardization for EGFR detection methods is needed to draw any conclusion concerning their activity in colorectal cancer.

A Case of Cap Polyposis Treated by Conservative Management / 대한소화기내시경학회지

Cap polyposis is a rare intestinal disease that is characterized by the presence of inflammatory polyps consisting of elongated, tortuous and distended crypts that are covered by a 'cap' of granulation tissue. The pathogenesis and proper treatment of cap polyposis are still unclear. We experienced a case of cap polyposis, that was treated successfully by conservative management without the need for a pharmacotherapy or resection.

A Case of Cap Polyposis Treated by Conservative Management / 대한소화기내시경학회지

Cap polyposis is a rare intestinal disease that is characterized by the presence of inflammatory polyps consisting of elongated, tortuous and distended crypts that are covered by a 'cap' of granulation tissue. The pathogenesis and proper treatment of cap polyposis are still unclear. We experienced a case of cap polyposis, that was treated successfully by conservative management without the need for a pharmacotherapy or resection.

Mutational Analysis of 17beta-hydroxysteroid dehydrogenase type 2 gene in Breast Cancers / 한국유방암학회지

PURPOSE : The 17beta-hydroxysteroid dehydrogenases(17HSDs) play an important role in the regulation of the physiologic activities of sex steroid hormones. The predominance of 17HSD type 1 in the malignant breast tissue could increase the estrogen-dependent proliferation and stimulate the cancer progression. On the other hand, the oxidative 17HSD type 2 may protect the normal breast cells from an excessive estradiol effect. To identify the role of 17HSD type 2 in the carcinogenesis of breast cancer, we investigate the mutation of 17HSD type 2 in 35 breast cancers. METHODS : We analyzed the entire coding region of the 17 HSD type 2 gene for detection of the somatic mutations in 35 invasive ductal carcinomas of the breast by polymerase chain reaction, single strand conformation polymorphism, and DNA sequencing. RESULTS : We found one missense mutation in exon 6(2.86%). It revealed the CCT-->CTT (Pro-->Leu) transition type at codon 262 in exon 6. CONCLUSION : In present study, we found only a mutation of the 17beta -HSD type 2 gene in breast cancer and could not demonstrate the direct relationship between the mutation of the 17beta -HSD type 2 gene and the development of breast cancer. These results suggest that the mutation of 17HSD type 2 doesn? play a major role in the development of breast cancer.

Mutational Analysis of 17beta-hydroxysteroid dehydrogenase type 2 gene in Breast Cancers / 한국유방암학회지

PURPOSE : The 17beta-hydroxysteroid dehydrogenases(17HSDs) play an important role in the regulation of the physiologic activities of sex steroid hormones. The predominance of 17HSD type 1 in the malignant breast tissue could increase the estrogen-dependent proliferation and stimulate the cancer progression. On the other hand, the oxidative 17HSD type 2 may protect the normal breast cells from an excessive estradiol effect. To identify the role of 17HSD type 2 in the carcinogenesis of breast cancer, we investigate the mutation of 17HSD type 2 in 35 breast cancers. METHODS : We analyzed the entire coding region of the 17 HSD type 2 gene for detection of the somatic mutations in 35 invasive ductal carcinomas of the breast by polymerase chain reaction, single strand conformation polymorphism, and DNA sequencing. RESULTS : We found one missense mutation in exon 6(2.86%). It revealed the CCT-->CTT (Pro-->Leu) transition type at codon 262 in exon 6. CONCLUSION : In present study, we found only a mutation of the 17beta -HSD type 2 gene in breast cancer and could not demonstrate the direct relationship between the mutation of the 17beta -HSD type 2 gene and the development of breast cancer. These results suggest that the mutation of 17HSD type 2 doesn? play a major role in the development of breast cancer.

A Case of Gastric CD56+ Extranodal NK/T-cell Lymphoma, Nasal Type / 대한소화기내시경학회지

A NK/T cell lymphoma is highly aggressive lymphoma of a putative NK-cell origin with a predominant extranodal presentation and a rapidly fatal course. CD56 has been reported to be the most reliable marker for a NK/T cell lymphoma. A NK/T cell lymphoma is strongly associated with the Epstein-Barr virus. We report a case of an aggressive NK/T cell lymphoma presenting as a gastric ulcer. A 52-year-old female patient presented with hematochezia and fever. The endoscopic finding showed a gastric ulcer with a recent bleeding stigma. Histologically, the gastric biopsy showed a diffuse infiltration of small or medium sized lymphoma cells with an angiocentric growth pattern and necrosis. The lymphoma cells were CD56+, CD3+, CD20-, which are consistent with a NK/T cell lymphoma. Unfortunately, the patient was discharged without treatment. We report this case with a review of the relevant literature.

Categorization and Evaluation of Usefulness of Breast Lesions with using Ultrasound BI-RADS (Breast Imaging Reporting and Data system)

PURPOSE: The aim of our study was to determine the positive predictive value (PPV) and to evaluate the usefulness of ultrasound BI-RADS, as compared with the histologic results of breast lesions that were categorized and classified by the ultrasound BI-RADS lexicon. MATERIALS AND METHODS: Between January and December 2004, the ultrasound features of 471 breast lesions in 368 patients were analyzed and categorized with using ultrasound BI-RADS. All of the lesions were compared with the histological results. We categorized category 2 and 3 lesions as benign lesions, and category 4 and 5 lesions as malignant lesions. We then calculated the sensitivity, specificity, positive predictive value, negative predictive value and accuracy. RESULTS: The breast lesions were histologically diagnosed as 298 cases of category 2, 21 cases of category 3, 108 cases of category 4 and 44 cases of category 5. The categorical malignancy rate was 1% (3/298) in category 2 lesions, 4.7% (1/21) in category 3 lesions, 8.3% (9/108) in category 4 lesions and 90.9% (40/44) in category 5 lesions. Within category 4, the malignancy rate for category 4a lesions was 5.4% (5/92), the malignancy rate for category 4b lesions was 1.3% (1/8) and the malignancy rate for category 4c lesions was 50% (4/8). The sensitivity, specificity, positive predictive value and negative predictive value were 90.6%, 75.1%, 31.6% and 98.4%, respectively. The statistically valid ultrasound features that were correlated with malignancy were an ill defined margin, a microlobulated mass, an irregular mass, inhomogenic echogenicity, an echogenic halo and an older patient age. CONCLUSION: Ultrasound BI-RADS was useful in differentiating benign from malignant breast lesions.

Recurrence Patterns and Clinical Behavior of Gastrointestinal Stromal Tumors (GISTs)

PURPOSE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) tract, and account for 1% of all GI malignancies. GISTs have a highly variable clinical course, and recurrent disease sometimes develops despite curative treatment. Although there are several known risk factors for recurrence, there are few adequate treatment strategies. This study evaluated the clinical behavior and clinicopathological characteristics, and examined correlation between recurrence and the prognostic factors. METHODS: From March 1999 to December 2005, 41 patients, with GISTs confirmed by a pathologic examination after a surgical resection, were enrolled. The patients were evaluated by immunohistochemical staining for CD117, CD34 and smooth muscle actin, and were classified according to the NIH criteria. RESULTS: The mean age was 58.9 years and the GISTs were mainly located in the stomach (56%) and small bowel (32%). With a median follow-up of 17.4 months, recurrence of the disease occurred in nine (22%) patients, with the liver being the main organ involved. According to the NIH criteria, there were 2 very low risk tumors, 11 low risk, 16 intermediate, and 12 high risk diagnosed. Gender was found to have predictive value for a recurrence (P=0.05). CONCLUSION: The primary site and gender have predictive value for a recurrence. Identifying the risk factors for recurrent disease may be useful for planning follow-up schedules. Further study involving more cases and a long-term follow-up will be needed. In addition, pathologic and immunohistoche-mical studies will be required to reduce the recurrence rate after a resection and to improve the patients' outcome.

The Effect of Etidronate Disodium on Rat's Bone and Soft Tissue

OBJECTIVE: To evaluate the effects of etidronate disodium on bone and soft tissue, especially on bone mineral density, and mucosal changes of the aorta and esophagus. METHOD: Male Sprague-Dawley rats were randomly divided into 2 separate groups: one with etidronate disodium and one without etidronate disodium. Bone mineral density (BMD) in lumbar vertebrae, femur, and a simple X-ray of the whole body were obtained. The abdominal aorta and esophagus were assessed histopathologically in post treatment. RESULTS: In post treatment for 12 weeks, the extent of decrease in BMD of the group with etidronate disodium was less than that of the group without etidronate disodium (p<0.05). There was no evidence of aorta and heart valve calcification in the simple X-ray, nor was there intima-media thickening, atheroma formation and calcification in aorta and esophageal irritation findings in pathologic examinations in both groups. CONCLUSION: The results suggested that etidronate disodium had an inhibitory effect on bone mineral loss and had the esophageal tolerability and safety, but no difference in aorta calcification and antiarthrogenic effects, including aorta wall thickness in this study.

Loss of PTEN Expression in Breast Cancers

Background : PTEN, located on chromosome 10q23.31, is a novel tumor suppressor gene. In the sporadic breast cancers, the incidence of the loss of heterozygosity of PTEN is approximately 10% to 40%, but the incidence of intragenic mutation of PTEN is less than 1%. To as- sess the role of the PTEN in the invasive ductal breast cancer, we studied the frequency of the loss of PTEN expression, its correlation with the commonly used prognostic factors of the breast cancer and with PTEN promoter hypermethylation status. Methods : Immunohistochemical staining with an anti-PTEN protein antibody was performed on the paraffin-embedded breast tissues from 129 women with a diagnosis of invasive ductal carcinoma. Methylation specific PCR was performed to detect hypermethylation in the PTEN gene on the 28 cases with the loss of PTEN expression. Results : Sixty-two (48%) of 129 breast tumors had the loss of PTEN expression. The loss of PTEN expression was correlated with lymph node metastasis and stage, and there was a near-significant correlation with the tumor size. PTEN promoter hypermethylation was found in five (18%) out of 28 patients. Conclusion : These results suggest that the loss of PTEN expression might play a role in the progression of the breast cancer and that the aberrant promoter methylation is one of the silencing mechanisms of PTEN.

Expression of Hypoxia Inducible Factor-1alpha in Invasive Squamous Cell Carcinoma of Uterine Cervix Treated by Radiotherapy

BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) is an intrinsic marker of tumor hypoxia, and this is associated with reduced radiosensitivity. Furthermore, HIF-1alpha can increase a tumor's aggressiveness by promoting neoangiogenesis, cell proliferation and survival, and invasion. METHODS: The expression of HIF-1alpha was was investigated by performing immunohistochemistry on the cervical tissue specimens obtained from 57 patients who had received radiotherapy combined with or without chemotherapy for stages I-III cervical squamous cell carcinoma. The staining results were compared with anemia, the stage, the radiotherapy response and patient survival by univariate and multivariate analysis. RESULTS: In 57 patients, the expression of HIF-1alpha was seen in the tissue specimens of 46 patients (81.7%). Among them, 25 (54.3%), 14 (30.4%), and 7 (15.2%) of the patients' tissue specimens showed weak, moderate and strong expressions, respectively. Six patients had a partial response after radiotherapy. Twelve patients (21.1%) died of cervical cancer. The increased expression of HIF-1alpha was significantly associated (p<0.05) with the disease stage and anemia. There were significant positive correlations between the increased expression of HIF-1alpha and the poor response after radiotherapy and the patients' survival. CONCLUSIONS: The present result suggests that the overexpression of HIF-1alpha in the uterine cervix could be used as a prognostic indicator for the patients treated with radiotherapy.

Complete Removal of a Breast Mass by US-guided Mammotome Biopsy: Histologic Assessment by Marginal Sampling

PURPOSE: The aim of this study was to assess whether the complete removal of a breast mass using ultrasound (US) guided mammotome biopsy was successful using a marginal biopsy after insuring the total visual excision of the breast mass on US images. The relationship of complete breast mass removal, and the hematoma, mass size and shape were also evaluated. MATERIALS AND METHODS: A US guided mammotome biopsy was performed in a total of 136 cases in 133 patients, with marginal biopsies also added when the complete removal of breast mass had been identified by sonography. The results of the marginal biopsies were serially dividing into three groups, as follows: group I were the cases in the initial 6 months, group II after the initial 6 months and group III having undergone two marginal biopsies. The marginal biopsies were performed in four directions around the probe, with "marginal positivity" defined as the same histopathological findings to that of the main mass in at least one direction. A statistical analysis was also used to evaluate between the marginal positivity and the hematoma, mass size and shape. RESULTS: The marginal positivities of groups I, II and III were 48.8, 29.4 and 45.5%, respectively. The marginal positivity of those with a lobular shaped mass was significantly higher (p=0.0121) than those with round or oval shaped masses (61.5 vs. 33.7 vs. 50%), but showed no statistical relationship with hematoma size of the lesions CONCLUSION: Although the lesions were removed by US using a US-guided mammotome biopsy, many residual lesions were still histologically present in the marginal samplings, especially in the lobular shaped masse

Gefitinib Trial in a Fanconi's Anemia Patient with Multiple Squamous Cell Carcinomas and Hepatocellular Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

FA (Fanconi's Anemia) is an autosomal recessive disorder that is characterized by pancytopenia with bone marrow hypoplasia, diverse congenital abnormalities and an increased predisposition towards malignancy. The mainstay of the treatment for these cancers has been surgery, because of the hypersensitive reactions of FA patients to DNA cross- linking agents or radiation. Therefore, there has been no effective therapy for advanced squa mous cell carcinoma. We report here on a patient suffering from advanced multiple squamous cell carcinoma and hepatocellular carcinoma along with an FA, and this patient was treated with gefitinib.

Questionable Role of Human Herpesvirus-8 in the Pathogenesis of Multiple Myeloma

BACKGROUND: Human herpesvirus 8 (HHV-8) has been strongly implicated in the etiopathogenesis of multiple myeloma. Cytokines, especially interleukin-6, that are produced by HHV-8 infected bone marrow stromal cells may play a role in the proliferation of neoplastic plasma cells. Viral DNA sequences have been detected in the bone marrow and peripheral blood cells of myeloma patients. Yet some investigators have not found the same results. METHODS: We exmined the presence of HHV-8 DNA in the paraffin-embedded cell block specimens of bone marrow aspirations from 26 patients with multiple myeloma by polymerase chain reaction (PCR) with KS330(233) primers. Thirteen cases of bone marrow aspirations from patients with other diseases were used as a negative control. The DNA extracted from the BC-1 cell line was used as a positive control. Immunohistochemistry using commercially available HHV-8 antibody was done in the cases that were proven HHV-8 DNA-positive by PCR. RESULTS: One case (3.9%) among the 26 patients with myleoma was positive for HHV-8 DNA by PCR, but no positive cells were detected in this case by immunohistochemistry. CONCLUSIONS: We could not find a clear relation between myeloma and HHV-8 in Korean patients examined in the present study.

A Case of Idiopathic Localized Hypertrophic Pachymeningitis Presented with Partial Seizures / 대한간질학회지

Idiopathic hypertrophic pachymeningitis is a clinical disorder caused by a localized or diffuse thickening of the dura mater, with an associated chronic inflammation. This can be diagnosed when there is no evidence of other etiologies such as trauma, infection, tumors, and Wegener's disease. Clinical manifestations are chronic headache with or without neurological manifestations such as cranial nerve palsies, cerebellar ataxia, neuro-ophthalmologic complications, and rarely clinical seizures. We described a patient with simple partial seizures with focal sensory and motor symptoms in the right hand as an initial and the only clinical manifestation, accompanied by a tumor-like lesion in the left parietal convexity on brain MRI. The patient underwent a lesionectomy, and the seizures have been well controlled so far without immunosuppressant treatment.

RUNX3 Methylation Status in Colonic Carcinoma and Adenoma

BACKGROUND: RUNX3 is expressed throughout the luminal gastrointestinal tract. RUNX3 is on chromosome 1p36, a location considered to carry an important tumor suppressor for many types of cancers. Epigenetic silencing of RUNX3 is causally related to human gastric cancer. METHODS: Colorectal cancers, adenoma, and the corresponding normal mucosa were obtained from 26 individual patients. To identify methylation of RUNX3 in colonic carcinogenesis, methylation-specific PCR was performed. RESULTS: RUNX3 methylation was found in one case of colonic carcinoma. The normal mucosa and tubular adenoma of this case had no methylation. No other cases were found to have methylations. CONCLUSIONS: These results are very different from the findings of gastric carcinomas, where frequent DNA methylation in the vicinity of the RUNX3 promoter is found. Although, the possibility of a role of RUNX3 methylation in the colon can not be completely ruled out, these results suggest that methylation of the RUNX3 promoter region might not contribute to the adenoma-carcinoma sequence of the colon.

Comparison of Ziehl-Neelsen Stain and TB-PCR on Detection of Mycobacterium tuberculosisin Formalin-fixed, Paraffin-embedded Tissues of Chronic Granulomatous Inflammation

BACKGROUND: TB-PCR is a faster and more sensitive method to detect mycobacterium than acid-fast bacilli (AFB) stain, which is laborious and time consuming. We compared the sensitivity and specificity of AFB stain and TB-PCR and examined the possibility of TB-PCR as a confirmative test without AFB stain in the diagnosis of tuberculosis. METHODS: We performed Ziehl-Neelsen stain and nested PCR using a commercially available TB-PCR kit amplifying IS6110 sequence in 81 cases of paraffin-embedded tissues diagnosed as chronic granulomatous inflammation. In addition, we evaluated the morphology of granuloma and the presence of caseation necrosis. RESULTS: Of the 81 cases studied, 22 (27.2%) and 40 (49.4%) were positive for AFB stain and TB-PCR, respectively. Of 49 cases accompanying caseation necrosis, 19 (38.8%) were AFB stain positive and 37 (75.5%) were TB-PCR positive; a result that is comparable with that of other reports. Of the 22 AFB-positive cases, 2 were TB-PCR negative. CONCLUSION: TB-PCR is very helpful for the diagnosis of tuberculosis in routinely processed, formalin-fixed, paraffin-embedded tissue samples. Nevertheless, AFB stain should continue to be performed at the same time.

KAI-1 Protein Expression in Breast Cancer: Correlation with Axillary Lymph Node Metastasis and other Prognostic Factors

BACKGROUND: KAI-1 is a metastasis suppressor gene. We have evaluated the correlationbetween KAI-1 protein expression in ductal carcinomas of the breast and axillary lymph nodemetastasis. METHODS: The expression of KAI-1 protein was confirmed by immunohistochemistryto examine breast tissues of ductal carcinomas from 50 patients with nodal metastasisand from 53 patients without metastasis. Western blot analysis was performed on fresh frozenbreast tissues from 17 cases with nodal metastasis and from 19 cases without metastasis. RESULTS: Immunohistochemical KAI-1 protein expression was decreased or negative in 39out of 50 cases with metastasis (78%), compared with 8 out of 53 cases with no metastasis(15.1%). The difference was statistically significant (p<0.05). Immunohistochemical KAI-1protein expression was significantly decreased in cases with higher modified Black's nucleargrade (p=0.027) and larger tumor size (p=0.039). Western blot analysis showed positivebands at 29.5 kDa in 8 out of 19 cases without metastasis (42.1%), and none of the 17 caseswith metastasis showed positive bands (p=0.0024). CONCLUSION: These results suggest thepossibility that KAl-1 might play a major role of a metastasis suppressor gene in addition tothe part it plays in the growth and progression of human breast ductal carcinoma. In addition, the decreased expression of KAI-1 protein in breast ductal carcinomas could be used as afactor suggesting poor prognosis.