Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma

위영찬,문아림,정민정,김예슬,방성식,장기석,백승삼,신수진 대한병리학회 2018 Journal of Pathology and Translational Medicine Vol.52 No.6

Background: BRCA1-associated protein 1 (BAP1) mutations are frequently reported in clear cell renal cell carcinoma (ccRCC); however, very few studies have evaluated the role of these mutations in other renal cell carcinoma (RCC) subtypes. Therefore, we analyzed BAP1 protein expression using immunohistochemistry in several RCC subtypes and assessed its relationship with clinicopathological characteristics of patients. Methods: BAP1 expression was immunohistochemically evaluated in tissue microarray blocks constructed from 371 samples of RCC collected from two medical institutions. BAP1 expression was evaluated based on the extent of nuclear staining in tumor cells, and no expression or expression in < 10% of tumor cells was defined as negative. Results: Loss of BAP1 expression was observed in ccRCC (56/300, 18.7%), chromophobe RCC (6/26, 23.1%), and clear cell papillary RCC (1/4, 25%), while we failed to detect BAP1 expression loss in papillary RCC, acquired cystic disease-associated RCC, or collecting duct carcinoma. In ccRCC, loss of BAP1 expression was significantly associated with high World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (p = .002); however, no significant correlation was observed between loss of BAP1 expression and survival in ccRCC. Loss of BAP1 expression showed no association with prognostic factors in chromophobe RCC. Conclusions: Loss of BAP1 nuclear expression was observed in both ccRCC and chromophobe RCC. In addition, BAP1 expression loss was associated with poor prognostic factors such as high WHO/ISUP grade in ccRCC.

Bacterial Ball as an Unusual Finding in Patients With Chronic Rhinosinusitis

김동규,위영찬,신수진,장연일,김경래,조석현 대한이비인후과학회 2018 Clinical and Experimental Otorhinolaryngology Vol.11 No.1

Objectives. Pathophysiology of chronic rhinosinusitis (CRS) is very complex and has not yet been clearly understood. To date, various factors have been researched to have relations with the pathogenesis of CRS, such as superantigens and biofilms. Recently, we found an unusual pathological finding in patients with CRS, and we called this new entity as bacteria ball (or bioball). In this study, we analyze the clinical characteristics of bacteria ball occurred in CRS. Methods. This study enrolled consecutive 247 patients with CRS who underwent functional endoscopic sinus surgery from January 2015 to August 2016. The diagnosis of bacterial ball was made when negative in Gomori-methenamine-silver stain and positive in Gram stain. Histologically, bacterial ball was defined as acellular mucous materials with bacterial colonies and inflammatory cell infiltrates. We compared clinical data and computed tomography (CT) findings between fungal and bacterial balls. Results. Six cases (2.4%) of CRS were confirmed histologically as bacterial ball. Most of them were found in the maxillary sinus of CRS without nasal polyposis (66.7%). Bacterial ball was green or brown colored materials similar to fungal ball which was harder and tightly adherent to the antral mucosa. Compared to fungal ball, patients with bacterial ball showed significantly less peripheral eosinophils (P=0.011) and calcification in CT scans (P=0.003). Conclusion. Bacterial ball is unusual findings occurred in patient with CRS which is different from fungal ball and biofilm. For diagnosis of bacterial ball, Gram stain is essentially required to identify bacterial colonies. Bacterial ball might appear to be evidence of a new strategy for living in the paranasal sinuses.

The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma

정유민,위영찬,김예슬,방성식,양정호,장기석,민경환,백승삼 대한병리학회 2018 Journal of Pathology and Translational Medicine Vol.52 No.1

Background: Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma. Methods: Combined expression patterns based on Smad4+/– and PTEN+/– status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed. Results: Smad4–/PTEN– status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p < .001). When Smad4–/PTEN– and Smad4+/PTEN+ groups were compared, Smad4–/PTEN– status was associated with high N stage (p = .018) and defective mismatch repair proteins (p = .006). Significant differences in disease-free survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4–/PTEN+ or Smad4+/PTEN–, and Smad4–/PTEN–) (all p < .05). Conclusions: Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.

상부 위장관 침범을 동반한 궤양성 대장염 1예

강혜진,윤병철,위영찬,백승삼 대한내과학회 2017 대한내과학회 추계학술대회 Vol.2017 No.1

Wnt7a Deficiency Could Predict Worse Disease-Free and Overall Survival in Estrogen Receptor-Positive Breast Cancer

이기종,민경환,위영찬,김예슬,신수진,정민성,장기석,백승삼 한국유방암학회 2017 Journal of breast cancer Vol.20 No.4

Purpose: Wnt7a is a glycoprotein involved in embryonic development and the progression of different types of malignant tumors. This study aimed to detect the level of Wnt7a expression in breast cancer and explore its role in the disease progression and prognosis. Methods: A total of 258 patients diagnosed with invasive ductal carcinoma of the breast were included in this study. Using tissue microarray and immunohistochemical staining, we evaluated the association between Wnt7a expression and clinicopathological parameters, and the prognostic value of Wnt7a. Results: Wnt7a expression was significantly correlated with estrogen receptor (ER) expression (odds ratio, 3.95; 95% confidence interval [CI], 1.99–7.80; p<0.001). On univariate and multivariate analyses, loss of Wnt7a expression was associated with poor disease-free survival (DFS) (multivariate hazard ratio [HR], 9.12; 95% CI, 1.80–46.09; p=0.008), but not with poor overall survival (OS). In the ER-positive group (n=114), loss of Wnt7a expression was an independent prognostic factor for shorter DFS (multivariate HR, 13.54; 95% CI, 1.11–165.73; p= 0.042) and OS (multivariate HR, 4.76; 95% CI, 1.29–17.61; p=0.019) on univariate and multivariate analyses. However, in the ER-negative group, there was no significant difference in DFS and OS according to Wnt7a expression. Conclusion: The loss of Wnt7a expression might be a meaningful factor in assessing DFS and OS, especially in ER-positive breast cancer.

Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma

이기종,김현성,정유민,안혜인,심종민,위영찬,표주연,송영수,백승삼,오영하 대한병리학회 2016 Journal of Pathology and Translational Medicine Vol.50 No.5

Background: Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown. Methods: Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between Ecadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated. Results: E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p < .001) but was not correlated with patient’s survival. Thirty-two cases (13.3%) showed at least focal nuclear Prrx-1 immunoreactivity while all non-neoplastic livers (n = 22) were negative. Prrx-1 expression was not associated with E-cadherin loss, survival or recurrence rates, pathologic factors, or the Ki-67 labeling index. Twenty tumors that were positive for E-cadherin and Prrx-1 had significantly higher nuclear grades than the rest of the cohort (p = .037). In Cox proportional hazard models, E-cadherin loss and large vessel invasion were independent prognostic factors for shorter disease-free survival. Cirrhosis and high Ki-67 index (>40%) were independent prognostic factors for shorter overall survival. Conclusions: Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.