PURPOSE: Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either KIT or platelet-derived growth factor receptor A (PDGFRA) and are highly responsive to several selective tyrosine kinase inhibitors. In this study, a targeted next-generation sequencing (NGS) assay with an Oncomine Focus Assay (OFA) panel was used for the genetic characterization of molecular targets in 30 Korean patients with GIST. MATERIALS AND METHODS: Using the OFA that enables rapid and simultaneous detection of hotspots, single nucleotide variants (SNVs), insertion and deletions (Indels), copy number variants (CNVs), and gene fusions across 52 genes relevant to solid tumors, targeted NGS was performed using genomic DNA extracted from formalin-fixed and paraffin-embedded samples of 30 GISTs. RESULTS: Forty-three hotspot/other likely pathogenic variants (33 SNVs, 8 Indels, and 2 amplifications) in 16 genes were identified in 26 of the 30 GISTs. KIT variants were most frequent (44%, 19/43), followed by 6 variants in PIK3CA, 3 in PDGFRA, 2 each in JAK1 and EGFR, and 1 each in AKT1, ALK, CCND1, CTNNB1, FGFR3, FGFR4, GNA11, GNAQ, JAK3, MET, and SMO. Based on the mutation types, majority of the variants carried missense mutations (60%, 26/43), followed by 8 frameshifts, 6 nonsense, 1 stop-loss, and 2 amplifications. CONCLUSIONS Our study confirmed the advantage of using targeted NGS with a cancer gene panel to efficiently identify mutations associated with GISTs. These findings may provide a molecular genetic basis for developing new drugs targeting these gene mutations for GIST therapy.

BACKGROUND: While qualitative analysis of methylation has been reviewed, the quantitative analysis of methylation has rarely been studied. We evaluated the methylation status of CDKN2A, RARbeta, and RASSF1A promoter regions in non-small cell lung carcinomas (NSCLCs) by using pyrosequencing. Then, we evaluated the association between methylation at the promoter regions of these tumor suppressor genes and the clinicopathological parameters of the NSCLCs. METHODS: We collected tumor tissues from a total of 53 patients with NSCLCs and analyzed the methylation level of the CDKN2A, RARbeta, and RASSF1A promoter regions by using pyrosequencing. In addition, we investigated the correlation between the hypermethylation of CDKN2A and the loss of p16INK4A immunoexpression. RESULTS: Hypermethylation of CDKN2A, RARbeta, and RASSF1A promoter regions were 16 (30.2%), 22 (41.5%), and 21 tumors (39.6%), respectively. The incidence of hypermethylation at the CDKN2A promoter in the tumors was higher in undifferentiated large cell carcinomas than in other subtypes (p=0.002). Hyperrmethylation of CDKN2A was significantly associated with p16INK4A immunoexpression loss (p=0.045). With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of p16INK4A immunoexpression (p=0.016). Squamous cell carcinoma and undifferentiated large cell carcinoma showed p16INK4A immunoexpression loss more frequently. The Kaplan-Meier survival curves analysis showed that methylation level and patient survival were barely related to one another. CONCLUSION: We quantitatively analyzed the promoter methylation status by using pyrosequencing. We showed a significant correlation between CDKN2A hypermethylation and p16INK4A immunoexpression loss.
Carcinoma, Large Cell ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; DNA Methylation ; Evaluation Studies as Topic ; Genes, p16 ; Genes, Tumor Suppressor ; Humans ; Incidence ; Kaplan-Meier Estimate ; Lung ; Methylation ; Promoter Regions, Genetic ; Receptors, Retinoic Acid ; Sequence Analysis, DNA ; Tumor Suppressor Proteins

BACKGROUND AND OBJECTIVES: Recent studies have reported that vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha are up-regulated in BRAF(V600E)-positive papillary thyroid carcinoma (PTC). We investigated whether papillary thyroid microcarcinomas (PTMCs) also exhibited increased expression of VEGF and HIF-1alpha. In addition, we analyzed the relationship between BRAF(V600E) mutation and clinicopathological parameters, as well as HIF-1alpha expression in PTMC. MATERIALS AND METHODS: We retrospectively selected 225 patients with PTMC. Immunohistochemical staining for HIF-1alpha and VEGF was performed using paraffinembedded PTMC tissue microarrays. BRAF(V600E) mutation status was analyzed by dideoxy sequencing. RESULTS: PTMCs larger than 0.5 cm tend to be related to aggressive clinicopathological features such as thyroid capsular invasion (p=0.023) and bilaterality (p=0.047). Immunoreactivity to HIF-1alpha (20.7%) and VEGF (30.2%) was more prominent in PTMCs as compared to normal follicular cells. However, HIF-1alpha and VEGF expression was not correlated with clinicopathological features. BRAF(V600E) mutation was found in 70.7% (159/225) of the PTMC cases. PTMCs harboring the BRAF(V600E) mutation exhibited larger tumor sizes as compared to PTMCs without the BRAF(V600E) mutation (p=0.038). However, BRAF(V600E) mutation status did not correlate with the expression of HIF-1alpha (p=0.623) or VEGF (p=0.990). CONCLUSION: HIF-1alpha and VEGF were more frequently detected in PTMCs as compared to normal thyroid tissues. However, BRAF(V600E) mutation status was not correlated with the expression of HIF-1alpha or VEGF in PTMCs.
Carcinoma ; Carcinoma, Papillary ; Humans ; Hypoxia-Inducible Factor 1 ; Proto-Oncogene Proteins B-raf ; Retrospective Studies ; Thyroid Gland ; Thyroid Neoplasms ; Vascular Endothelial Growth Factor A

Here we report a case of Strongyloides stercoralis infection of the gastric and pancolonic mucosa in a 79-year-old female with a monoclonal gammopathy of undetermined significance. Endoscopic biopsies were performed in gastric antrum, cecum, distal ascending colon, and hepatic flexure of the colon. On microscopic examination, there were many adult worms, larvae and eggs in the gastric and colonic mucosa. Worms, larvae, and eggs were located in the crypts and within the lumen of the crypts. The body wall of the adult worm was composed of cuticle and a weak muscle layer. A routine stool examination failed to detect larvae or ova. Based on the histopathologic examination, these parasites were confirmed as S. stercoralis.
Adult ; Aged ; Biopsy ; Cecum ; Colon ; Colon, Ascending ; Eggs ; Female ; Humans ; Larva ; Monoclonal Gammopathy of Undetermined Significance ; Mucous Membrane ; Muscles ; Ovum ; Paraproteinemias ; Parasites ; Pyloric Antrum ; Stomach ; Strongyloides stercoralis ; Strongyloidiasis

Here we report a case of Strongyloides stercoralis infection of the gastric and pancolonic mucosa in a 79-year-old female with a monoclonal gammopathy of undetermined significance. Endoscopic biopsies were performed in gastric antrum, cecum, distal ascending colon, and hepatic flexure of the colon. On microscopic examination, there were many adult worms, larvae and eggs in the gastric and colonic mucosa. Worms, larvae, and eggs were located in the crypts and within the lumen of the crypts. The body wall of the adult worm was composed of cuticle and a weak muscle layer. A routine stool examination failed to detect larvae or ova. Based on the histopathologic examination, these parasites were confirmed as S. stercoralis.
Adult ; Aged ; Biopsy ; Cecum ; Colon ; Colon, Ascending ; Eggs ; Female ; Humans ; Larva ; Monoclonal Gammopathy of Undetermined Significance ; Mucous Membrane ; Muscles ; Ovum ; Paraproteinemias ; Parasites ; Pyloric Antrum ; Stomach ; Strongyloides stercoralis ; Strongyloidiasis

PURPOSE: Phyllodes tumors (PTs) of the breast have been classified as benign, borderline, or malignant based on their histopathologic features. However, predicting clinical behavior based on these features has proven to be difficult given that local recurrence occurs in both benign and malignant PTs. Recurrence has been shown to mirror the histologic pattern of the primary tumor or to show dedifferentiation. The aim of this study was to assess the value of the histopathologic parameters, expression or mutation of c-Kit and platelet derived growth factor receptor alpha (PDGFRA) in predicting tumor recurrence. METHODS: Representative areas from 39 benign, 16 borderline, and 12 malignant PTs were selected for construction of tissue microarrays. Immunohistochemical analyses for p53, Ki-67, c-Kit, and PDGFRA were performed and SSCP-PCR analysis was carried out to identify mutations in exons 9, 11, 13, and 17 of the c-Kit gene and exons 12 and 18 of the PDGFRA gene. Clinicopathologic features, including tumor recurrence and margin status, were also evaluated. RESULTS: Of the 67 PTs, 11 cases (16.4%) recurred from 3 to 92 months following initial diagnosis (4 benign, 2 borderline, and 5 malignant). One benign PT case recurred as a borderline tumor and two borderline PT cases recurred as malignancies. Three patients died of malignant PT. No mutations of the c-Kit or PDGFRA genes were found and there was no statistically significant association of either p53 or p16 immunostaining with recurrent disease (p>0.05). However, histologic grade (p=0.033), margin status (p<0.001), Ki-67 (p=0.012), c-Kit (p=0.002), and PDGFRA (p=0.007) stromal immunopositivity were significantly correlated with recurrence. CONCLUSION: Even though positive or close margins were significantly associated with tumor recurrence, stromal c-Kit, PDGFRA positivity, and the Ki-67 index were useful for predicting recurrent PTs. Despite this, no c-Kit or PDGFRA mutations were found.
Breast ; Exons ; Humans ; Phyllodes Tumor ; Proto-Oncogene Proteins c-kit ; Receptors, Platelet-Derived Growth Factor ; Recurrence

BACKGROUND AND OBJECTIVES: The postoperative cheek cyst with orbital involvement is a rare condition and the treatment of eroded orbital floor is controversial. This study evaluated the efficacy of endoscopic marsupialization for treating postoperative cheek cyst with orbital floor defect and assessed the requirements of a direct orbital approach for orbital reconstruction. MATERIALS AND METHODS: The study involved a retrospective review of twelve patients with postoperative cheek cyst and orbital floor defect. Medical records were reviewed for details of previous surgery, presenting symptoms, surgical approach and the results of the operation. The maximum diameter of the involved orbital floor was calculated using the coronal imaging of paranasal sinus computed tomography (PNS CT). RESULTS: All patients had previously undergone Caldwell-Luc procedures. The most common symptom was pressure on the cheek. According to PNS CT, the maximum diameter of the involved orbital floor ranged from 0.7 to 3.1 cm (mean 1.46 cm) and the involved orbital area ranged from 0.35 to 4.23 cm2 (mean 1.87 cm2). All patients underwent only endoscopic marsupialization without orbital reconstruction. Postoperatively, all patients showed no recurrence of symptoms or required revision surgery. CONCLUSION: Endoscopic marsupialization without reconstruction of the orbital floor could be considered as a first treatment option for postoperative cheek cyst combined with orbital floor defect.
Cheek ; Cytochrome P-450 CYP1A1 ; Endoscopy ; Floors and Floorcoverings ; Humans ; Maxillary Sinus ; Medical Records ; Mucocele ; Orbit ; Recurrence ; Retrospective Studies

PURPOSE: A CXCR4/stroma derived factor-1alpha (SDF-1alpha, CXCL12) interaction is involved in many metastatic cancer mechanisms, including breast cancer. The primary objectives of this study were to investigate the correlation between CXCR4 and axillary lymph node metastasis and to clarify the interaction between CXCR4 in primary tumor cells and SDF-1alpha in metastatic lymph nodes. An analysis of the correlation between CXCR4, SDF-1alpha and clinicopathologic features was also performed. METHODS: Representative areas from 44 invasive ductal carcinomas were selected for construction of tissue microarrays using a 5 mm punch. Breast cancers (n=44), metastatic axillary lymph nodes (n=18) and non-metastatic axillary lymph nodes (n=26) were immunohistochemically stained for CXCR4, SDF-1alpha, estrogen receptor (ER), progesterone receptor (PR) and HER2. The parameters of age, tumor size, nuclear grade, histologic grade, lymph node status and pathologic node (pN) stage pN0 to pN3 were evaluated. RESULTS: CXCR4 expression was negatively correlated with increased age (p=0.005) and positively correlated with a large tumor size (p=0.043) and PR expression (p=0.027). CXCR4 expression was not correlated with metastatic lymph nodes (p=0.079) and SDF-1alpha expression in metastatic lymph nodes (p=0.062). However, CXCR4 nuclear positivity is correlated with lymph node metastasis (p=0.044). SDF-1alpha was not correlated with any clinicopathologic feature in a statistically significant manner. CONCLUSION: An evaluation of young age, large tumor size and PR expression helps predict lymph node metastasis and poor prognosis. Expression of CXCR4 nuclear positivity is correlated with a poor prognosis.
Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Chemokine CXCL12 ; Estrogens ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Receptors, Progesterone

Malignant deciduoid mesothelioma is a rare malignant neoplasm occurring in the peritoneum of young women. We report a case of malignant deciduoid mesothelioma that occurred in the omentum of a 47-year-old woman. The patient had never exposed to asbestos and had no history of cesarean section. The lesions were multiple infiltrative nodules affected the peritoneal cavity, omentum, and surface of the uterus with both ovaries. Microscopically, the nodules were composed of mesothelial cells similar to decidual cells
Asbestos ; Cesarean Section ; Female ; Humans ; Mesothelioma* ; Middle Aged ; Omentum ; Ovary ; Peritoneal Cavity ; Peritoneum ; Pregnancy ; Uterus

BACKGROUND: Liquid-based cytology is currently known as an effective method, and cervical cytology has been shown to be especially effective from of malignancy detection. In our study, the cytological detection rates of the Thinprep (Liquid-based cytology) and conventional cytology (bronchial washing & brushing) for endobronchial lesions were compared. METHODS: Between July 2005 and September 2005, the data from 30 patients with respiration symptom, who had shown abnormal lesion on bronchoscopy, were collected. RESULTS: The bronchoscopic biopsy group was consisted of 30 cytodiagnosis specimens, 24 of which were confirmed to be malignant. The others were tuberculosis (4), bronchiectasis and bronchopulmonary fistula (1 each). Of the 24 malignant case, cancer or atypical cells were detected in 19, 17 and 12 of the Thinprep, brushing cytology and washing cytology cases, respectively. None one of the methods detected cancer cells in the non-malignant specimens. Washing cytology has shown sensitivity, specificity, and positive and negative predictive values of 50, 100, 100 and 33.3% respectively. Brushing cytology has shown sensitivity, specificity, and positive and negative predictive values of 70.8, 100, 100 and 46.2%, respectively. Thinprep has shown sensitivity, specificity, and positive and negative predictive values of 79.2, 100, 100 and 54%, respectively. CONCLUSIONS: Thinprep (liquid-based cytology) showed better sensitivity and negative predictive values for the evaluation of lung cancer than conventional cytology. However a large-scale study will be needed in the future.
Biopsy ; Bronchiectasis ; Bronchoscopy* ; Cytodiagnosis ; Fistula ; Humans ; Lung Neoplasms ; Respiration ; Tuberculosis