Kwang Sun Suh

Prevalence of human papillomavirus DNA in various histological subtypes of cervical adenocarcinoma: a population-based study

The role of human papilloma virus (HPV) infection in the development of cervical carcinoma is well established, however, the prevalence of HPV DNA in cervical adenocarcinoma varies from study to study. It appears to be caused by a number of factors, one of which is that cervical adenocarcinomas comprise a heterogeneous group of multiple subtypes. To clarify the impact of HPV infection on the development of cervical adenocarcinoma with diverse histological subtypes, we performed a population-based study in Korean women from 15 different institutes for the status of HPV infection in adenocarcinoma of uterine cervix. A total of 432 cervical adenocarcinomas from 1997 to 2001 were reviewed and classified according to the modified WHO classification. For 135 cases, HPV typing was performed with HPV DNA chip (82 cases) and PCR HPV typing (53 cases), using formalin-fixed, paraffin-embedded archival tissue. The overall prevalence of HPV infection in cervical adenocarcinoma was 90%. The infection of HPV 16 and/or HPV 18 accounted for 78% of HPV-positive adenocarcinomas. Multiple HPV types were found in 13% of the cases. The HPV DNA was rarely detected in minimal deviation adenocarcinoma. Interestingly, HPV 16 was a predominant type in endometrioid and villoglandular types, whereas HPV 16 and HPV 18 were detected with equal prevalence in other subtypes. In conclusion, HPV infection, mostly HPV 16 and HPV 18, is highly associated with most of the cervical adenocarcinomas, whereas endometrioid and villoglandular type have a different pattern of HPV infection status. Minimal deviation adenocarcinoma does not seem to be related with HPV infection.

Leiomyoma of the ovary mimicking mucinous cystadenoma

We present a case of ovarian leiomyoma of a 46-year-old woman with a history of a palpable lower abdominal mass. A multiloculated multiseptated mainly cystic mass in the left adnexa on computed tomography (CT) was initially considered to be an ovarian mucinous cystadenoma. This mass, however, was proved to be a left ovarian vascular leiomyoma on the surgical pathology.

Benign Metastasizing Leiomyoma: Metastasis to Rib and Vertebra

Benign metastasizing leiomyoma is very rare and characterized by the presence of pelvic, peritoneal, nodal, or pulmonary nodules in women with a history of uterine leiomyomas. We report a case of benign metastasizing leiomyoma in a 30-year-old woman who had undergone a prior myomectomy due to uterine cellular leiomyoma 3 years earlier. The patient had a mass on the right sixth rib and 2 masses in the sixth thoracic vertebra. Pathologically, these masses were diagnosed as cellular leiomyomas. Estrogen and progesterone receptors were both positive in the metastatic tumors as well as in the uterine leiomyomas. The diagnosis of benign metastasizing leiomyoma can only be made after careful examination of the primary tumor to exclude small foci of malignant change.

Rifampin-associated tubulointersititial nephritis and Fanconi syndrome presenting as hypokalemic paralysis

BackgroundRifampin is one of the most important drugs in first-line therapies for tuberculosis. The renal toxicity of rifampin has been reported sporadically and acute tubulointerstitial nephritis (ATIN) is a frequent histological finding. We describe for the first time a case of ATIN and Fanconi syndrome presenting as hypokalemic paralysis, associated with the use of rifampin.Case presentationA 42-year-old man was admitted with sudden-onset lower extremity paralysis and mild renal insufficiency. He had been treated for pulmonary tuberculosis with isoniazid, rifampin, and ethambutol for 2 months. Laboratory tests revealed proteinuria, profound hypokalemia, hyperchloremic metabolic acidosis with a normal anion gap, positive urine anion gap, hypophosphatemia with hyperphosphaturia, hypouricemia with hyperuricosuria, glycosuria with normal serum glucose level, generalized aminoaciduria, and β2-microglobulinuria. A kidney biopsy revealed findings typical of ATIN and focal granular deposits of immunoglubulin A and complement 3 in the glomeruli and tubules. Electron microscopy showed epithelial foot process effacement and electron-dense deposits in the subendothelial and mesangial spaces. Cessation of rifampin resolved the patient’s clinical presentation of Fanconi syndrome, and improved his renal function and proteinuria.ConclusionThis case demonstrates that rifampin therapy can be associated with Fanconi syndrome presenting as hypokalemic paralysis, which is a manifestation of ATIN. Kidney function and the markers of proximal tubular injury should be carefully monitored in patients receiving rifampin.

MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix.

BackgroundMicroRNA (miRNA) expression is known to be deregulated in cervical carcinomas. However, no data is available about the miRNA expression pattern for the minimal deviation adenocarcinoma (MDA) of uterine cervix. We sought to detect deregulated miRNAs in MDA in an attempt to find the most dependable miRNA or their combinations to understand their tumorigenesis pathway and to identify diagnostic or prognostic biomarkers. We also investigated the association between those miRNAs and their target genes, especially Notch1 and Notch2.MethodsWe evaluated miRNA expression profiles via miRNA microarray and validated them using.real-time PCR assays with 24 formalin-fixed, paraffin-embedded tissue blocks of MDA and 11 normal proliferative endocervical tissues as control. Expression for Notch1 and 2 was assessed by immunohistochemistry.ResultsMiRNA-135a-3p, 192-5p, 194-5p, and 494 were up-regulated, whereas miR-34b-5p, 204-5p, 299-5p, 424-5p, and 136-3p were down-regulated in MDA compared with normal proliferative endocervical tissues (all P <0.05). Considering the second-order Akaike Information Criterion consisting of likelihood ratio and number of parameters, miR-34b-5p showed the best discrimination power among the nine candidate miRNAs. A combined panel of miR-34b-5p and 194-5p was the best fit model to discriminate between MDA and control, revealing 100% sensitivity and specificity. Notch1 and Notch2, respective target genes of miR-34b-5p and miR-204-5p, were more frequently expressed in MDA than in control (63% vs. 18%; 52% vs. 18%, respectively, P <0.05). MiR-34b-5p expression level was higher in Notch1-negative samples compared with Notch1-positive ones (P <0.05). Down-regulated miR-494 was associated with poor patient survival (P = 0.036).ConclusionsMDA showed distinctive expression profiles of miRNAs, Notch1, and Notch2 from normal proliferative endocervical tissues. In particular, miR-34b-5p and 194-5p might be used as diagnostic biomarkers and miR-494 as a prognostic predictor for MDA. The miR-34b-5p/Notch1 pathway as well as Notch2 might be important oncogenic contributors to MDA.

Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors

Background/Aims The diagnosis of gastrointestinal stromal tumors (GIST) relies on the demonstration of KIT expression, but KIT expression is absent or reduced in approximately 15% of GIST. Methods Eighty-one GISTs were diagnosed between January 1998 and December 2007 at the Department of Pathology at both Chungnam National University Hospital and Eulji University Hospital, Daejeon. Medical history, patient follow-up, and radiographic data were collected if available in the medical records. To determine diagnostic and prognostic markers for GISTs focused on PDGFRA mutation and clinicopathologic features, we analyzed 81 GIST cases for KIT, PDGFRA, DOG1, and p16 expression and for mutation of PDGFRA genes. Results Among 81 GIST cases, 20 high risk cases (24.7%) were recurred or metastasized. Immunohistochemically, KIT was positive in 76 (93.8%), PDGFRA in 75 (92.7%), and DOG1 in 77 (95.1%). With a cutoff value of 50%, p16 expression was positive in 26 cases were positive (32.1%). A correlation between p16 expression or negative DOG1 expression and recurrence or metastasis was demonstrated (p<0.05). Four cases showed a missense mutation in exon 12 of PDGFRA gene, three of these were of epithelioid GISTs. Two cases showed a silent mutation in exon 18 of PDGFRA. Conclusions These results indicate that the expression of DOG1 and PDGFRA is observed in a majority of GIST cases. Expression of p16 and negative DOG1 expression is predictive for development of recurrence and/or metastasis. Even though mutation of the PDGFRA gene is frequently seen in epithelioid GISTs, a clinicopathologic correlation was not demonstrated.

Treatment with Medroxyprogesterone Acetate Plus Levonorgestrel-releasing Intrauterine System for Early-stage Endometrial Cancer in Young Women: Single-arm, Prospective Multicenter Study: Korean Gynecologic Oncology Group Study (KGOG2009)

A prospective multicenter trial has been started in Korea to investigate the treatment efficacy of a levonorgestrel-releasing intrauterine system plus medroxyprogesterone acetate in young women with early-stage endometrial cancer. A number of studies have reported the effectiveness of hormonal therapy using systemic progestin in women clinically diagnosed with early endometrial adenocarcinoma at Stage IA, Grade 1, who want to maintain reproductive potential. In addition, several recent studies reported the use of a levonorgestrel-releasing intrauterine system to treat patients at a high risk of perioperative complications who cannot tolerate systemic progesterone because of its adverse effects. However, there has been no prospective multicenter trial that investigated the effectiveness of treatment with systemic progesterone in combination with intrauterine progesterone in young women with endometrial cancer. Young patients with histologically confirmed Grade 1 endometrioid adenocarcinoma that is presumably confined to the endometrium, who desired to preserve their fertility potential, undergo levonorgestrel-releasing intrauterine system insertion and are administered medroxyprogesterone acetate at a dosage of 500 mg/day concurrently. The follow-up and treatment response assessment were implemented at a 3-month interval with office endometrial aspiration biopsy with the levonorgestrel-releasing intrauterine system in place, and dilatation and curettage after removal of the levonorgestrel-releasing intrauterine system. The primary endpoint is the complete response rate. The secondary endpoint is to estimate the consistency of the results of the office endometrial aspiration biopsy with the levonorgestrel-releasing intrauterine system in the uterus and a dilatation and curettage after removal of the levonorgestrel-releasing intrauterine system.

Morphometric Analysis of Podocyte Foot Process Effacement in IgA Nephropathy and Its Association with Proteinuria

The effacement of podocyte foot processes is a well-known phenomenon occurring in many glomerulonephritides with proteinuria. The fundamental sign of IgA nephropathy is hematuria, but proteinuria also frequently occurs. The authors measured the extent of foot process effacement in 100 IgA nephropathy cases with proteinuria and correlated it with the amount of proteinuria. The extent of foot process effacement was greater in the nephrotic proteinuria group than in the subnephrotic proteinuria or control groups. The degree of foot process effacement was positively correlated with proteinuria. This study demonstrates that proteinuria in IgA nephropathy is closely related to foot process effacement.

Differential expression of DUSP6 with expression of ERK and Ki-67 in non-small cell lung carcinoma

Dual specificity phosphatase 6 (DUSP6) is a member of the MAP kinase phophatase family. DUSP6 inactivates extracellular signal-regulated kinase (ERK), belonging to the MAP kinase family, and can act in tumor suppressive pathways. The aim of this study was to investigate associations of DUSP6 expression with expression of ERK and Ki-67 and with clinicopathological parameters in lung adenocarcinoma and squamous cell carcinoma. A total of 102 squamous cell carcinomas and 66 adenocarcinomas were studied using immunohistochemistry for DUSP6, ERK1/2, and Ki-67. In 66 adenocarcinomas, high DUSP6 expression was positively correlated with ERK1/2 expression. High DUSP6 expression was correlated with lower histological grade and lower Ki-67 index in the adenocarcinomas. In 102 squamous cell carcinomas, high DUSP6 expression was correlated with lower ERK expression, with greater smoking pack-years, but not with the Ki-67 index. These results indicate that DUSP6 acts as a negative feedback regulator of ERK in adenocarcinoma progression, but that DUSP6 does not play a role in the downregulation of ERK in squamous cell carcinoma. The differential expression of DUSP6 correlated with Ki-67 index, suggesting that DUSP6 plays an important role in cancer resistance in different subtypes of non-small cell lung carcinoma.

Excision repair cross-complementation group 1 expression predicts response and survival in locally advanced cervical carcinoma patients treated with concurrent chemoradiotherapy

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