Prognostic Significance of CD109 Expression in Patients with Ovarian Epithelial Cancer

BACKGROUND: Ovarian epithelial cancer (OEC) is the second-most common gynecologic malignancy. CD109 expression is elevated in human tumor cell lines and carcinomas. A previous study showed that CD109 expression is elevated in human tumor cell lines and CD109 plays a role in cancer progression. Therefore, this study aimed to determine whether CD109 is expressed in OEC and can be useful in predicting the prognosis. METHODS: Immunohistochemical staining for CD109 and reverse transcription-quantitative polymerase chain reaction was performed. Then we compared CD109 expression and chemoresistance, overall survival, and recurrence-free survival of OEC patients. Chemoresistance was evaluated by dividing into good-response group and poor-response group by the time to recurrence after chemotherapy. RESULTS: CD109 expression was associated with overall survival (p = .020), but not recurrence-free survival (p = .290). CD109 expression was not an independent risk factor for overall survival due to its reliability (hazard ratio, 1.58; p = .160; 95% confidence interval, 0.82 to 3.05), although we found that CD109 positivity was related to chemoresistance. The poor-response group showed higher rates of CD109 expression than the good-response group (93.8% vs 66.7%, p = .047). Also, the CD109 mRNA expression level was 2.88 times higher in the poor-response group as compared to the good-response group (p = .001). CONCLUSIONS: Examining the CD109 expression in patients with OEC may be helpful in predicting survival and chemotherapeutic effect.

Primary Glomerulonephritis with Unique C4d Deposition and Concurrent Non-infectious Intermediate Uveitis: a Case Report and Literature Review

C4 glomerulopathy is a recently introduced entity that presents with bright C4d staining and minimal or absent immunoglobulin and C3 staining. We report a case of a 62-year-old man with C4 glomerulonephritis (GN) and uveitis. He presented to the nephrology department with proteinuria and hematuria. The patient also had intermediate uveitis along with proteinuria and hematuria. A kidney biopsy that was performed in light of continuing proteinuria and hematuria showed a focal proliferative, focal sclerotic glomerulopathy pattern on light microscopy, absent staining for immunoglobulin or C3 by immunofluorescence microscopy, with bright staining for C4d on immunohistochemistry, and electron-dense deposits on electron microscopy. Consequently, C4 GN was suggested as the pathologic diagnosis. Although laser microdissection and mass spectrometry for glomerular deposit and pathologic evaluation of the retinal tissue were not performed, this is the first report of C4 GN in Korea and the first case of coexisting C4 GN and uveitis in the English literature.

The Role of TWIST in Ovarian Epithelial Cancers

BACKGROUND: Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway. METHODS: We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1alpha (HIF1alpha), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters. RESULTS: The expression of TWIST, E-cadherin, HIF1alpha, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1alpha expression and reduced E-cadherin expression. The altered HIF1alpha/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS. CONCLUSIONS: Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1alpha/TWIST/E-cadherin pathway may play an important role in the progression of OEC.

Pathology of Thrombotic Microangiopathy

Thrombotic microangiopathy (TMA) is a microvascular thrombotic lesion caused by endothelial injury and subsequent formation of platelet rich thrombus. TMA is first described as a classical pathologic feature of HUS/TTP. Renal biopsy finding of TMA represents kidney involvement of HUS/TTP as well as other diseases such as malignant hypertension, drug toxicity, eclampsia, pre-eclampsia, and several systemic infections. Autoimmune diseases and transplant kidney sometime also have TMA. It is needed to consider a complete autoimmune work-up of patients presenting with TMA including tests for ANA, ANCA, and ADAMTS13 inhibitory antibodies, because there are several reports of association with TMA in patients of SLE, anti-phospholipid syndrome, and ANCA-associated vasculitis.

Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers

BACKGROUND: Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis. METHODS: Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC). RESULTS: CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers. CONCLUSIONS: The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy.

Ectomesenchymal Chondromyxoid Tumor in the Anterior Tongue: Case Report of a Unique Tumor

Ectomesenchymal chondromyxoid tumor (ECMT) is a rare tumor, exclusively arising in the anterior tongue. Thirty-eight cases have been reported in the English literature. It usually presents as a sessile protrusion and shows round to spindle cells embedded in myxoid to chondroid stroma. Tumor cells are almost always positive for polyclonal glial fibrillary acidic protein (GFAP). We report our experience in the recent treatment of a case of ECMT, the third case in 3 years. The mass in the anterior tongue revealed characteristic morphologic features of ECMT and the expression of polyclonal GFAP. Although ECMT should be differentiated from other mesenchymal tumors including myoepithelioma, its clinical, morphological, and immunohistochemical features enable its diagnosis, especially when pathologists are aware of it.

A Case of Severe Acute Kidney Injury by Near-Drowning

Acute kidney injury (AKI) secondary to near-drowning is rarely described and poorly understood. Only few cases of severe isolated AKI resulting from near-drowning exist in the literature. We report a case of near-drowning who developed to isolated AKI due to acute tubular necrosis (ATN) requiring dialysis. A 21-yr-old man who recovered from near-drowning in freshwater 3 days earlier was admitted to our hospital with anuria and elevated level of serum creatinine. He needed five sessions of hemodialysis and then renal function recovered spontaneously. Renal biopsy confirmed ATN. We review the existing literature on near-drowning-induced AKI and discuss the possible pathogenesis.

Clinicopathologic Factors for Prediction of Lymph Node Metastasis in Submucosally Invasive Colorectal Carcinoma

PURPOSE: The purpose of this study is to identify useful clinicopathologic factors for the prediction of lymph node metastasis in submucosally invasive colorectal carcinoma. METHODS: A total of fifty-four cases of colorectal carcinomas with submucosal invasion were included. The patients underwent curative resection with en bloc lymph node dissection. Clinical features such as age, gender, tumor size and tumor location were reviewed. Histopathologic examinations for tumor growth type, differentiation, depth of tumor invasion, lymphovascular invasion, neural invasion, tumor budding and peritumoral inflammation were performed. The expression of E-cadherin, beta-catenin, Smad4, p53 and Ki-67 were examined by immunohistochemistry. The correlation between the clinicopathologic factors and lymph node metastasis was evaluated. RESULTS: From the 54 patients with submucosally invasivecolorectal carcinoma, lymph node metastasis was identified in 13 cases (24.1%). The incidence of lymph node metastasis was significantly higher in cases positive for lymphovascular invasion (55.6% vs. 17.8%, P=0.028) and positive for tumor budding (47.4% vs. 11.45%, P=0.006). Cases negative for Smad4 had a higher tendency for incidence of lymph node metastasis (28.6% vs. 15.8%, P=0.341). Other clinicopathologic and immunohistochemical features were irrelevant to the lymph node status. In multivariate analysis, only tumor budding was an independent predictor of lymph node metastasis (P=0.051). CONCLUSION: Lymphovascular invasion and tumor budding were predictive factors of lymph node metastasis in submucosally invasive colorectal carcinoma. The incidence of lymph node metastasis of submucosally invasive colorectal carcinoma was not low. Careful selection for avoiding surgery in submuocally invasive colorectal carcinoma should be considered.

Molecular Biological Characteristics of Differentiated Early Gastric Cancer on the Basis of Mucin Expression

BACKGROUND: It is clear that the biologic characteristics of gastric cancer are different on the basis of mucin phenotypes. However, there are unabated controversies on the exact biologic differences of mucin expression in gastric cancer. METHODS: We analyzed various protein expressions and microsatellite instability (MSI) status based on mucin expression in 130 differentiated early gastric adenocarcinoma cases. Furthermore, we evaluated the genomic alternation in 10 selected differentiated early gastric adenocarcinoma cases using array based comparative genomic hybridization (aCGH). RESULTS: Intestinal mucin predominant subtype showed significantly elevated p53 protein and caudal-related homeobox 2 expression, and delocalization of beta catenin expressions compared to the gastric mucin predominant subtype. On MSI status, the gastric mucin predominant subtype more frequently showed unstable status than the intestinal mucin predominant subtype. CGH study showed more frequent chromosomal gain and loss in the intestinal mucin predominant subtype than the gastric mucin predominant subtype, albeit without statistical significance. Interestingly, there were significant differences in chromosomal alternation between four mucin phenotypes. CONCLUSIONS: Study results suggest possible different points of biologic behaviors in early differentiated gastric adenocarcinomas by mucin expression type.

Clinical Relevance of Elevated Levels of Serum Soluble Interleukin-2 Receptor alpha (sIL-2Ralpha) in Patients with Non-Hodgkin's Lymphoma / 대한진단검사의학회지

Levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) are known to increase in the sera of patients with certain malignancies, including malignant lymphoma. This study aimed to assess the clinical significance of the sIL-2Ralpha level in non-Hodgkin's lymphoma (NHL). We used ELISA to measure the sIL-2Ralpha levels in 48 newly diagnosed and untreated patients with NHL and evaluated the correlation between the sIL-2Ralpha levels and clinical characteristics and the International Prognostic Index (IPI). We monitored serum sIL-2Ralpha in 7 patients to compare the changes in their clinical progress with these levels. High levels of serum sIL-2Ralpha (> or =2,000 U/mL) correlated well with parameters defining the high risk group according to the IPI, i.e., high tumor burden at diagnosis (stage III+IV) and lactate dehydrogenase > or =472 U/L. The levels were also associated with B symptoms, bone marrow involvement, and poor response to therapy. The sIL-2Ralpha level decreased during complete remission and was elevated during disease progression or relapse. A high level of sIL-2Ralpha was significantly associated with a low survival rate. These results suggest that serum sIL-2Ralpha might be useful as a biomarker for evaluating the prognosis of patients with NHL at the time of diagnosis and during therapy. A well-controlled, large-scale study is needed to clarify the clinical significance of sIL-2Ralpha in specific groups of NHL.

Expression of p63 and its Isoform, deltaNp63, in Non-Small Cell Lung Carcinoma

BACKGROUND: Several studies have been conducted on the role of the p63 gene family in non-small cell lung carcinoma (NSCLC). Nevertheless, the role of these genes in the development and progression of NSCLC remains controversial. This study was designed to examine the expression and clinicopathologic significance of the p63 family in NSCLC. METHODS: Immunohistochemical staining was performed on 92 cases of NSCLC (47 squamous cell carcinomas [SqCCs] and 45 adenocarcinomas [ACs]) using tissue microarray blocks. The results were analyzed and correlated with clinicopathologic data. RESULTS: The expression of delta Np63 (Delta Np63) was elevated in SqCC (39/47), but not in AC (2/45; p<0.01). Both p63 and Delta Np63 had high expression in 39 SqCCs; p63 and Delta Np63 also had a similar geomorphologic distribution in most positive tumors. The expression of Delta Np63 was correlated with histologic type, gender, pT stage, p53 expression, and p63 expression. pT and pN stages were independent factors in survival (p<0.05, respectively). CONCLUSIONS: The major p63 isoform in NSCLC, Delta Np63, had a strong correlation with p53 and p63, and was exclusively expressed in SqCC. However, our findings suggest that Delta Np63 was not an independent prognostic factor for NSCLC.

Effects of Supplementation with a Selective COX-2 Inhibitor and Vitamin C on Glomerular TGF-beta, COX-2, and Antioxidant Activity in Rats with Passive Heymann Nephritis / 대한신장학회지

PURPOSE: In the passive Heymann nephritis (PHN) rat model of membranous nephropathy, complement induces glomerular epithelial cell injury and proteinuria, which is partially mediated by reactive oxygen species (ROS), TGF-beta, and COX-2. In the current study, we determined the effect of a selective COX-2 inhibitor (celecoxib) and vitamin C on the enzyme system associated with ROS, TGF-beta, and COX-2 in PHN. METHODS: Four groups of rats with PHN were dosed with polyethylene glycol vehicle (P; n=4), celecoxib (COXi; n=8), vitamin C (VC; n=8), or celecoxib and vitamin C (COXi+VC; n=8) from days 7-21. Each group was then divided into 2 subgroups reflecting the day of the experiment (day-14 and -21 subgroups). RESULTS: The urine protein was significantly reduced in the VC and COXi+VC groups (subgroup day- 14) compared to the P group (p<0.05). The glomerular TGF-beta expression was reduced in the COXi+ VC group (subgroup day-21) compared to the P group (p<0.05). Glomerular COX-2 expression was increased in the COXi, VC, and COXi+VC groups compared to the P group (p<0.05). The COXi, VC, and COXi+VC groups (subgroup day-21) had decreased activity of lipid peroxide and xanthine oxidase and increased activity of xanthine dehydrogenase, superoxide dismutase, GSH-Px, and catalase. This antioxidant activity was highest in the COXi+VC group (p<0.05). CONCLUSION: Selective COX-2 inhibitors possess antioxidant effects. The combination of a COX-2 inhibitor and vitamin C was more effective than COX-2 inhibitor or vitamin C alone in increasing antioxidant activity and decreasing TGF-beta.

Post-treatment Effects of Erythropoietin and Nordihydroguaiaretic Acid on Recovery from Cisplatin-induced Acute Renal Failure in the Rat

5-Lipoxygenase inhibitor and human recombinant erythropoietin might accelerate renal recovery in cisplatin-induced acute renal failure rats. Male Sprague-Dawley rats were randomized into four groups: 1) normal controls; 2) Cisplatin group-cisplatin induced acute renal failure (ARF) plus vehicle treatment; 3) Cisplatin+nordihydroguaiaretic acid (NDGA) group-cisplatin induced ARF plus 5-lipoxygenase inhibitor treatment; 4) Cisplatin+erythropoietin (EPO) group-cisplatin induced ARF plus erythropoietin treatment. On day 10 (after 7 daily injections of NDGA or EPO), urea nitrogen and serum Cr concentrations were significantly lower in the Cisplatin+NDGA and Cisplatin+EPO groups than in the Cisplatin group, and 24 hr urine Cr clearances were significantly higher in the Cisplatin+EPO group than in the Cisplatin group. Semiquantitative assessments of histological lesions did not produce any significant differences between the three treatment groups. Numbers of PCNA(+) cells were significantly higher in Cisplatin, Cisplatin+NDGA, and Cisplatin+EPO groups than in normal controls. Those PCNA(+) cells were significantly increased in Cisplatin+NDGA group. These results suggest that EPO and also NDGA accelerate renal function recovery by stimulating tubular epithelial cell regeneration.

Effects of Celecoxib and Nordihydroguaiaretic Acid on Puromycin Aminonucleoside-Induced Nephrosis in the Rat

The selective cyclooxygenase-2 (COX-2) and 5-lipoxygenase (LOX) inhibitors might inhibit prostaglandin synthesis and reduce proteinuria. The present study was designed to investigate the anti-proteinuric effects of nordihydroguaiaretic acid (NDGA) as compared with celecoxib in puromycin aminonucleoside (PAN) nephrosis rats. Fifty five male Sprague-Dawley rats were divided into 4 groups; A, normal control; B, PAN group; C, PAN+COX-2 inhibitor (celecoxib) group; and D, PAN+5-LOX inhibitor (NDGA) group. After induction of PAN nephrosis through repeated injections of PAN (7.5 and 15 mg/100 g body weight), rats were treated with celecoxib, NDGA, or vehicle for 2 weeks. Twenty four hour urine protein excretions were significantly lower in PAN+celecoxib and PAN+NDGA groups than in PAN group. Serum creatinine (SCr) concentrations and 24 hr urine creatinine clearances (CCr) were not significantly different in the four groups. Electron microscopy showed that podocyte morphology was changed after the induction of PAN nephrosis and was recovered after celecoxib or NDGA administration. Celecoxib significantly recovered the expressions of nephrin, CD2AP, COX-2, and TGF-beta. NDGA also recovered TGF-betaexpression, but did not alter the expressions of nephrin, CD2AP and COX-2. The present study suggested that celecoxib and NDGA might effectively reduce proteinuria in nephrotic syndrome without impairing renal function.

Fine Needle Aspiration Cytology of Palpable Lymph Nodes: A Single Institutional Experience of 1,346 Cases / 대한세포병리학회지

The aim of this study was to evaluate the diagnostic value of fine needle aspiration cytology (FNAC) for the assessment of palpable enlarged lymph nodes. The authors reviewed the results of 1,346 FNACs of palpable enlarged lymph nodes performed at Pusan National University Hospital from 1998 to 2004. Of the 1,346 cases, 1,265 (94.0%) were satisfactory and 81 (6.0%) unsatisfactory. Cytologic diagnoses were judged in 488 cases, based on subsequent histologic diagnoses, clinical follow up, or both. Global results for all malignancies (lymphoid and non-lymphoid neoplasms) based on cases with final diagnoses, showed a sensitivity of 87.4% and a specificity of 98.7%. The overall diagnostic accuracy was 93.2%, and the false negative rate reduced from 12.6% to 7.3% when lymphomatous cases were excluded. The annual data for this period showed that the number of diagnostic lymph node biopsies and the rate of inadequately sampled material markedly decreased. Gene rearrangement studies for IgH and TCR gamma were helful in 30 cases. FNAC is a useful initial diagnostic procedure for the evaluation of palpable enlarged lymph nodes. However, the technique should be assisted by the appropriate ancillary studies and by proper interpretation by a cytopathologist.

Invasine Ductal Carcinoma with Osteoclast-Like Giant Cell in a Young Woman / 대한세포병리학회지

Mammary carcinoma with osteoclast-like giant cells is an unusual neoplasm characterized by giant cells, mononuclear stromal cells, and hemorrhage accompanying a low grade carcinoma. We present the cytological findings in a case of invasive ductal carcinoma with osteoclast-like giant cells that was initially confused with a fibroadenoma, due to its well-demarcated and soft mass and the young age of the patient. A 28-year-old female presented with a 4.5 cm, well demarcated, soft and nontender mass in the right breast. Fine needle aspiration cytology (FNAC) showed a combination of low grade malignant epithelial cell clusters and osteoclast-like giant cells. The atypical epithelial cells were present in cohesive sheets and clusters. Osteoclast-like giant cells and bland-looking mononuclear cells were scattered. An histological examination revealed the presence of an invasive ductal carcinoma with osteoclast-like giant cells. We report here the cytological findings of this rare carcinoma in a very young woman. The minimal atypia of the epithelial cells and its soft consistency may lead to a false negative diagnosis in a young woman. The recognition that osteoclastlike giant cells are rarely present in a low grade carcinoma, but not in benign lesion, can assist the physician in making a correct diagnosis.

Male Patients with the Diagnoses of Synchronous Prostate and Breast Cancer / 대한비뇨기과학회지

Prostate cancer and male breast cancer are similar in many ways, including the potential role of steroidal hormones in their pathogenesis and shared genetic abnormalities. However, the combination of these cancers in the same patient is rare. Herein, the case of a male patient, diagnosed with synchronous prostate and breast cancers, is reported.

Analysis of Microsatellite Instability in Ovarian Epithelial Cancer

BACKGROUND: The aim of this study was to clarify the incidence and role of microsatellite instability (MSI) in sporadic ovarian epithelial cancers (OEC). We investigated the MSI status and mismatch repair (MMR) protein expression in OEC. METHODS: MSI was examined by fluorescence- based polymerase chain reaction using five NCI panel markers (BAT25, BAT26, D2S123, D5S346 and D17S250) in 46 cases of OEC. Immunohistochemistry (IHC) for hMLH1 and hMSH2 was performed. RESULTS: Seven cases (15.2%) exhibited high-frequency MSI (MSIH), one exhibited low-frequency MSI (MSI-L), and the remaining 38 demonstrated microsatellite stability (MSS). MSI-H in OEC was not associated with histologic grade, FIGO stage, tumor size, mitoses or histologic type. Loss of expression of either hMLH1 or hMSH2 was observed in 4 of the 7 (59.3%) MSI-H cases, whereas 4 of the 39 (10.3%) MSI-L or MSS tumors revealed loss of expression of MMR proteins. The sensitivity and specificity of immunohistochemistry for hMLH1 and hMSH2 were 57.1% and 89.7%. CONCLUSIONS: Our data suggest that a genetic defect in the MMR system might play a role in the carcinogenesis of a minor subset of sporadic OEC however, immunohistochemical testing for hMLH1 and hMSH2 cannot accurately determine microsatellite instability status in OEC.

Primary Alveolar Soft Part Sarcoma of the Lung

Alveolar soft part sarcoma (ASPS) is a rare epithelial-like soft tissue sarcoma. The two main sites of its occurrence are the lower extremities in adults and the head and neck in children. Primary pulmonary involvement of this sarcoma, without evidence of soft tissue tumor elsewhere, is very exceptional. We present a case of primary ASPS of the lung in a 42-yr-old woman. A computed tomographic scan of the thorax demonstrated a well-circumscribed, solid tumor located in the right upper lobe. The mass was resected by right upper lobectomy. After 5 months, three metastatic lesions, involving lumbar vertebrae and occipital scalp, were found. Histologically, the tumor consisted of alveolar nests of large polygonal tumor cells, the cytoplasm of which frequently revealed periodic acid-Schiff-positive, diastase-resistant intracytoplasmic rod-like structures. On immunohistochemical staining, the tumor cells were positive only for vimentin and alpha-smooth muscle actin. Ultrastuctural study using electron microscopy revealed characteristic electron-dense, rhomboid intracytoplasmic crystals.

Alteration of G1/S Cell Cycle Regulatory Proteins in Ovarian Epithelial Tumors

BACKGROUND: Disturbances of the cell cycle regulatory proteins are key events underlying the development and/or progression of human malignancies. The aim of this study was to evaluate the expression of G1/S cell cycle regulatory proteins in ovarian epithelial tumor. METHODS: We simultaneously evaluated the expression of cyclin D1, cyclin E, CDK4, CDK2, p16, Rb, E2F1, p53 and the Ki67 labelling index (LI) by immunohistochemical methods in 148 cases of ovarian epithelial tumor of the benign (n=47), borderline (n=29), and malignant type (n=72). RESULTS: The expression of cyclin E, CDK2, p16, Rb, E2F1, p53 and the Ki67 LI gradually increased from the benign type, through the borderline type, to the malignant tumors. Between the borderline and malignant tumors, the increased expression of cyclin E, E2F1, and p53, and the decreased expression of Rb were significantly associated with malignancy. The reduced Rb expression and the increased E2F1 expression were correlated with the FIGO stage and the histologic grade in the malignant ovarian epithelial tumors. CONCLUSIONS: Cyclin E, E2F1, and p53 overexpressions and the loss of Rb are the important components during carcinogenesis of ovarian epithelial tumors. Our results suggest that in- creased expression of E2F1 should be considered as a new parameter for the prognosis of patients with malignant ovarian epithelial tumors.