[Show abstract][Hide abstract] ABSTRACT: We present here a case of extrathyroid CASTLE (the third case reported in the English literature) treated with excision and neck dissection without radiotherapy. Also, we reviewed the literature and analyzed the therapeutic results of each treatment modality for CASTLE. A 27-year-old male had initially presented with a painless, right neck mass for 2 months. Computed tomography of the neck showed a 3.8 x 3.2 x 3.8 cm heterogeneously enhancing mass at right level IIa, and no definite thyroid lesion was found. An excisional biopsy was done and the pathologic diagnosis was CASTLE. Then we performed a right modified radical neck dissection and right thyroid lobectomy. After three years, no evidence of tumor recurrence was noted. Total excision followed by neck dissection could be a sufficient surgical treatment option for CASTLE. Postoperative radiotherapy might be an alternative treatment option for neck dissection in patients with positive nodal status.
World Journal of Surgical Oncology 08/2014; 12(1):247. · 1.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Malignant transformation or recurrence of intracranial mature teratoma is an extremely rare occurrence, compared to the usual ovarian counterpart. Previously, yolk sac tumor elements have been considered to be selective progenitors of enteric-type adenocarcinoma arising from intracranial germ cell tumors. However, the present case demonstrates the occurrence of enteric-type adenocarcinoma in recurrent intracranial mature cystic teratoma 12 years after gross total removal, a case of which has not previously been documented in the literature. The 11.5-cm long, dura mater-based tumor on the right fronto-temporal lobe displaced the brain; however, the patient had no neurologic symptoms or discomfort other than pus-like discharge on the scalp. Microscopic examinations revealed a small focus of adenocarcinoma and dysplastic colonic mucosa in the mature cystic teratoma. No immature elements were seen. The cystic wall was almost denuded and showed an exuberant xanthogranulomatous reaction with foreign-body type giant cells engulfing keratin materials and cholesterol clefts, suggesting that chronic inflammation due to repeated cyst wall rupture and the previous resection may contribute to malignant transformation. The adenocarcinoma showed strong immunohistochemical expression of CK20 and p53, but CK7 in patches. The molecular profile of the adenocarcinoma showed a mutation in KRAS and wild-type BRAF, which might be associated with malignant transformation of intracranial mature teratomas. In conclusion, the intracranial mature teratomas should require long-term follow-up, and clinicians, radiologists and pathologists should be aware of the potential for malignant progression of recurrent intracranial mature cystic teratoma despite gross total resection and no neurologic symptoms.
[Show abstract][Hide abstract] ABSTRACT: Helicobacter pylori infection is linked to the development of gastric cancer. H. pylori-associated gastric inflammation is considered to be the first important step in the histogenesis of such neoplasia. However, studies that compare proteome of gastric mucosa infected with or without H. pylori are lacking.
[Show abstract][Hide abstract] ABSTRACT: MET, a cell surface receptor for hepatocyte growth factor, is involved in the development of triple-negative/basal-like breast cancer (TNBC/BLBC). However, its utility as a therapeutic target in this subtype of breast cancer is poorly understood. To evaluate MET fully as a potential therapeutic target for TNBC/BLBC, we investigated the relationship between MET expression and clinical outcomes of patients with breast cancer and the functional effect of MET inhibition. Using automated immunohistochemistry (Ventana), we analyzed MET expression in 924 breast cancer patients with relevant clinicopathologic parameters. BLBC showed the strongest relationship with MET expression (57.5%, p < 0.001). High expression of MET in breast cancer resulted in poor overall survival (p = 0.001) and disease-free survival (DFS, p = 0.010). MET expression was relatively high in TNBC cell lines, and the silencing of MET via small interfering RNA reduced cell proliferation and migration. We observed reduced TNBC cell viability after treatment with the MET inhibitor PHA-665752. In the most drug-resistant cell line, MDA-MB-468, which showed elevated epidermal growth factor receptor (EGFR) expression, silencing of EGFR resulted in increased sensitivity to PHA-665752 treatment. We confirmed that PHA-665752 synergizes with the EGFR inhibitor erlotinib to decrease the viability of MDA-MB-468 cells. TNBC patients coexpressing MET and EGFR showed significantly worse DFS than that in patients expressing EGFR alone (p = 0.021). Our findings strongly suggest that MET may be a therapeutic target in TNBC and that the combined therapy targeting MET and EGFR may be beneficial for the treatment of TNBC/BLBC patients.
International Journal of Cancer 05/2014; 134(10). · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: KRAS is one of commonly mutated genetic "drivers" in non-small cell lung cancers (NSCLCs). Recent studies indicate that patients with KRAS-mutated tumors do not benefit from adjuvant chemotherapy, so there is now a focus on targeting KRAS-mutated NSCLCs. A feasible mutation detection method is required in order to accurately test for KRAS status.
The Korean Journal of Pathology 04/2014; 48(2):100-7. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was aimed at investigating the relation of P2X7 receptor (P2X7R) expression with the clinicopathological features of papillary thyroid carcinoma (PTC) coexisting with Hashimoto's thyroiditis (HT).
We examined 170 patients (84, PTC with HT; 86, PTC without HT). P2X7R expression was examined by immunohistochemical methods. The staining intensity and patterns were evaluated and scored using a semi-quantitative method.
The PTC with HT group was more likely to contain women and had less extrathyroid extension, lymph node (LN) metastasis, lymphovascular invasion, and recurrence than the PTC without HT group. Patients positive for P2X7R had significantly higher frequencies of lymphovascular invasion, extrathyroid extension, LN metastasis, and absence of HT. As shown by multivariate analysis, the expression of P2X7R was significantly higher if HT was absent and extrathyroid extension was present. In the PTC with HT group, the expression of P2X7R was significantly higher in patients with tumor multifocality, lymphovascular invasion, and extrathyroid extension. In the PTC without HT group, the expression of P2X7R was significantly higher in women and those having tumor multifocality.
Coexistence of PTC with HT is associated with good prognostic factors, and P2X7R expression in PTC was correlated with poor prognostic factors and the absence of HT.
The Korean Journal of Pathology 02/2014; 48(1):30-5. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human papillomavirus (HPV) is an important prognostic factor for tonsillar squamous cell carcinoma (TSCC). HPV-positive and HPV-negative TSCCs are considered distinct in terms of prognosis and sensitivity to chemo/radiotherapy. However, to date, no study has thoroughly evaluated the individual prognostic factors for these two disease subgroups. Hepatocyte growth factor (HGF)-Met signaling pathway can be a predictive marker for prognosis or therapy response, especially in HPV-negative TSCC. We therefore investigated the prognostic values of HGF and c-Met expression in TSCC according to HPV status. Immunohistochemical analyses of HGF and c-Met protein expression and silver in situ hybridization of c-Met gene copy number were performed in 79 formalin-fixed paraffin-embedded specimens. In HPV-negative TSCC, HGF overexpression, regional lymph node category, and ipsilateral cervical nodal metastasis predicted decreased overall survival (OS) (P = .017, P = .024, and P = .003, respectively). The latter two were also independent prognostic factors for progression-free survival (PFS) (P = .023 and P = .002, respectively). In HPV-positive TSCC, heavy alcohol consumption and advanced primary tumor category were predictive of PFS, whereas no independent prognostic factor for OS was identified. HGF overexpression had a significant effect on OS in HPV-negative TSCC, but not in HPV-positive TSCC. HPV-negative/HGF-high expression tumors exhibited the worst survival outcomes, whereas HPV-positive/HGF-low expression tumors had the most favorable prognosis. c-Met expression and c-Met gene amplification were not associated with survival outcomes in TSCC patients. In conclusion, HGF may be a potential prognostic marker in HPV-negative TSCC, whereas c-Met exhibited limited clinical significance in TSCC.
[Show abstract][Hide abstract] ABSTRACT: Risk factors for lymph node metastasis in tonsillar squamous cell carcinoma (TSCC) need to be established to determine the degree of surgery required to achieve high curative rates. However, little is known currently about the histopathological features predicting prognosis, specifically in TSCC.
This study included 53 patients who underwent surgical resection with neck dissection. Clinicopathological factors investigated included age, gender, alcohol use, tobacco consumption, tumor stage, adjacent structure involvement, cell differentiation, squamous dysplasia, in situ carcinoma associated with primary invasive cancer, carcinoma in situ skip lesions, necrosis, invasive front, depth of invasion, and lymphatic, muscle, or perineural invasion.
Contralateral cervical metastasis was associated with higher T stages and soft palate invasion. Lymphatic and muscle invasion were associated with ipsilateral cervical metastasis. Advanced T stage, invasion to the base of tongue, and skip lesions were associated with decreased disease-free survival. Advanced T stage and skip lesions were associated with worse overall survival.
Advanced T stage and soft palate invasion may predict a high risk of contralateral nodal metastasis. T stage and skip lesion are worse prognostic factors in TSCC and should be commented in pathology reports.
The Korean Journal of Pathology 06/2013; 47(3):203-10. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Heterotopic gastrointestinal cysts are rarely found in the oral cavity. Most of these cysts are lined with gastric mucosa and involve the tongue. There have been no reported heterotopic intestinal cysts of the submandibular gland that are completely lined with colonic mucosa. An 8-year-old girl presented with an enlarging swelling in the left submandibular area, and a 4-cm unilocular cyst was fully excised. The cyst was completely lined with colonic mucosa that was surrounded by smooth muscle layer, and the lining cells were positive for CDX-2, an intestinal marker, indicating a high degree of differentiation. The pathogenesis remains unclear, but it may be related to the misplacement of embryonic rests within the oral cavity during early fetal development. Although heterotopic intestinal cysts rarely occur in the submandibular gland, they should be considered in the differential diagnosis of facial swellings in the pediatric population.
The Korean Journal of Pathology 06/2013; 47(3):279-83. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tonsillar squamous cell carcinomas (TSCC) frequently present with locally advanced diseases and cervical metastases, which are associated with poor prognoses. Epithelial-mesenchymal transition (EMT) is critical for tumor invasiveness and metastatic potential. Recent studies have shown that TWIST1-inducing EMT is overexpressed and hypermethylated in several cancers, indicating disease progression. The aim of the present study was to determine the clinical and prognostic significance of TWIST1 hypermethylation and EMT-related protein expression in TSCC. Methylation levels of TWIST1 promoter were analyzed by quantitative real-time methylation-specific polymerase chain reaction. Immunohistochemical analyses of TWIST1, Snail, and SMAD nuclear interacting protein-1 (SNIP1) were performed in 65 formalin-fixed, paraffin-embedded blocks of surgically resected specimens. TWIST1 promoter hypermethylation was found in 27.7% (18/65) of TSCCs. TWIST1 promoter hypermethylation was associated with poor differentiation (P = .012). Contralateral cervical lymph node metastasis was more frequently observed in TWIST1-methylated tumors (P = .029). High protein expressions of TWIST1, Snail, and SNIP1 were observed in 14 TSCC specimens (21.5%), 21 TSCC specimens (32.3%), and 38 TSCC specimens (58.5%), respectively. SNIP1 expression correlated significantly with TWIST1 methylation (P = .001), whereas TWIST1 protein expression did not. Contralateral cervical lymph node metastasis was an independent risk factor of the decreased overall survival rate (P = .002). TWIST1 methylation (P = .031) and pN stage (P = .037) were independent factors of poor prognoses affecting disease-free survival. TWIST1 promoter hypermethylation may be a useful molecular marker for predicting prognoses and contralateral cervical lymph node metastases in patients with TSCC.
[Show abstract][Hide abstract] ABSTRACT: The overexpression of tetraspanin CD151 - a transmembrane protein that promotes tumor invasion and metastasis - is associated with poor prognosis in various cancers. However, its clinical significance in non-small cell lung cancers (NSCLCs) has not been fully elucidated. We investigated CD151 expression status by immunohistochemical analysis in paraffin-embedded specimens obtained from 380 patients with surgically resected NSCLCs (245 squamous cell carcinomas [SCCs] and 135 adenocarcinomas [ADCs]) between 1994 and 2001. High CD151 expression was detected in 28.7% NSCLCs (20.8% of SCCs and 42.9% of ADCs) and was significantly associated with male gender, smokers, and ADCs. Moreover, elevated CD151 levels were correlated with reduced overall (OS) and disease-free survival (DFS), and were an independent negative prognostic factor for OS in NSCLC. According to histological type, high CD151 expression was an independent prognostic factor for lower OS in ADC, although not in each subtype, and the elevated CD151 expression levels were more common in solid-predominant tumors (48.3%). In contrast, there was no prognostic correlation in SCC. High CD151 expression appeared to correlate with aggressive behavior in NSCLC, suggesting that it may be a useful prognostic marker for lung ADC patients and a potential molecular target for NSCLC treatment.
Lung cancer (Amsterdam, Netherlands) 04/2013; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Endoscopic submucosal dissection (ESD) is a well-established method for the treatment of gastrointestinal epithelial tumors. However, the treatment of gastric subepithelial tumors (SETs) that originate from the muscularis propria layer still depends primarily on surgical techniques. We evaluated the appropriate indications for ESD in the treatment of SETs that originate from the muscularis propria layer. METHODS: Thirty-five patients with gastric SETs that originate from the muscularis propria layer who underwent ESD were enrolled, and the charts were retrospectively reviewed to investigate the parameters predictive complete resection and complications. RESULTS: The mean age of the patients was 54.15 ± 9.3 years, and the male/female ratio was 2:3. Twenty-eight of the 35 SETs (85.7 %) were movable, and 15 (45.7 %) had a positive rolling sign. The most frequent location of the SETs was high body (n = 14). The most common pathological diagnoses were leiomyoma (60 %) and gastrointestinal stromal tumor (28.6 %). The complete resection rate was 74.3 %. A positive rolling sign (p = 0.022) and small tumor size (≤20 mm; p = 0.038) were significantly associated with complete resection. Two patients (6.1 %) developed perforations that required surgical treatment; their SMTs were neurogenic tumors with fixed lesion. Tumor mobility was significantly associated with perforation (p = 0.017). CONCLUSIONS: The ESD method appears to be relatively safe for use in the complete resection of SETs that originate from the muscularis propria layer. Small tumor size (≤20 mm) and a positive rolling sign are appropriate indications for ESD.
[Show abstract][Hide abstract] ABSTRACT: Gastric serrated adenoma is a recently recognized entity that has been rarely described and poorly characterized. To examine whether gastric serrated adenoma shares the same immunophenotypic and molecular features of its colorectal traditional serrated adenoma, the clinicopathologic features, expression of mucin proteins (MUC2, MUC5AC, CD10, MUC6) and mismatch repair protein (MLH1), and mutations of BRAF and KRAS genes were studied. The nine serrated adenomas were obtained from five men and four women, with a mean age of 67 years. Seven (78%) serrated adenomas were located in the body of the stomach. The endoscopic findings were not sufficiently characteristic to diagnose serrated adenoma or serrated adenocarcinoma; however, most were elevated lesions. The initial biopsy material was available in all cases and the serrated features were evident in 6 cases diagnosed as adenoma. Among the nine cases, seven (78%) were associated with invasive adenocarcinoma within the serrated adenoma. MUC5AC was expressed in 6 serrated adenomas (67%). Expression of MUC5AC was observed in all tumors located in the lower third of the stomach. Focal MUC6 expression was observed in the basal part of two serrated adenomas. MLH1 expression was lost in two cases (22%). KRAS mutations were observed in three cases (33%) while BRAF mutations were not detected in any of the cases. Gastric serrated adenoma does not completely share the same immunophenotypic and molecular features of its colorectal counterpart. Gastric serrated adenomas are frequently associated with adenocarcinoma. When serrated adenoma is encountered in a gastric biopsy specimen, the possibility of associated adenocarcinoma should be considered in the adjacent stomach.
Histology and histopathology 02/2013; · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dermatofibrosarcoma protuberans (DFSP) is characterized genetically by the translocation t(17;22)(q22;q13), which creates a COL1A1/PDGFB fusion gene. The implications of this gene for the clinicopathologic features of the disease are not fully understood. Fifty-one cases of DFSP from 46 patients were reclassified as DFSP (n=29) and DFSP-fibrosarcomatous variant (DFSP-FS; n=22). Fluorescence in situ hybridization was performed using a dual-color break-apart probe to detect rearrangements involving PDGFB, and CD34 immunohistochemistry staining was done. The DFSP-FS was found in older patients, and the tumors were larger, with a smaller mean area of staining for CD34. PDGFB rearrangement was found in 45 cases (95.7%). The mean gene copy number was 3.82 (range 2.2-6.45) and was higher in DFSP-FS than in classic DFSP (4.54 vs. 3.47; P < .001). The PDGFB copy number showed a moderate positive correlation with the number of mitotic figures and tumor size. Patients undergoing wide excision or having no involvement of the resection margin had no relapses. These results suggest a role for COL1A1/PDGFB in sarcomatous change in DFSP over time. Detection of COL1A1/PDGFB rearrangement by fluorescence in situ hybridization is useful for confirmation of the diagnosis. Patients who present with metastatic DFSP-FS show less typical histologic findings and loss of CD34 staining, leaving PDGFB rearrangement as the preferred adjunctive method for diagnosis from small biopsies and for prediction of the value of imatinib therapy.
[Show abstract][Hide abstract] ABSTRACT: Human papillomavirus (HPV) infection has been demonstrated in some of the nonmelanoma skin cancers as well as in precancerous lesions. Multiple infections of mucosal high-risk HPV may contribute to the onset of digital Bowen's disease through, if any, digital-genital transmission. We screened for the presence of the mucosal HPV DNA in patients with extragenital Bowen's disease (n = 30), squamous cell carcinoma (n = 11), bowenoid papulosis (n = 9), verrucous carcinoma (n = 1), actinic keratosis (n = 5), and basal cell carcinoma (n = 5). We used a PANArray HPV Genotyping Chip for high-risk and low-risk mucosal types. Genotyping data was confirmed using a conventional direct DNA sequencing method. Two cases of extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. None of the squamous cell carcinoma cases were positive. Neither patients with digital Bowen's disease (n = 5) nor those with squamous cell carcinoma (n = 3) showed any mucosal high-risk HPV. Mucosal high-risk HPV DNA was confirmed in 5 (55.6%) of the 9 patients with bowenoid papulosis. HPV 16 was most prevalent (n = 3), while the DNA of HPVs 35 and 67 was detected in one sample for each of the two types. Our study demonstrated that two (6.7%) of the patients with 30 extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. HPVs belonging to the mucosal high-risk group may participate in the development of extragenital Bowen's disease. However, we could not find any relationship between the mucosal high-risk HPV and Bowen's disease or squamous cell carcinoma in the fingers.
BioMed research international. 01/2013; 2013:421205.
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: The development of anaplastic lymphoma kinase (ALK) inhibitor has just followed the recent discovery of ALK rearrangement in lung cancer, therefore not much is yet known about the clinical course and treatment outcomes to chemotherapy in ALK-positive patients. The purpose of this study was to investigate the clinical characteristics and treatment outcomes in patients with ALK-positive NSCLC treated with conventional chemotherapy during pre-ALK inhibitor period. PATIENTS AND METHODS: We retrospectively screened 381 consecutive NSCLC patients without known epidermal growth factor receptor (EGFR) or KRAS mutation who were diagnosed between 2007 and 2008 at a single center, and identified ALK rearrangements by fluorescence in situ hybridization. Additional 44 ALK-positive patients who were identified since 2009 by central lab for participation on clinical trial were included for the analysis of clinical outcomes. RESULTS: Of the 381 tumors screened, 21 (5.6%) showed ALK rearrangements, with twenty adenocarcinomas and one pleomorphic carcinoma. Of 65 ALK-positive patients including additional 44 ALK-positive patients, 32 patients received pemetrexed as a second- or further-line therapy, in whom the response rate was 34.4% (11/32), median progression-free survival (PFS) was 4.0 months (range: 0-22.0 months) and median overall survival (OS) was 50.8 months (95% confidence interval [CI]: 38.7-62.8). CONCLUSIONS: The prevalence of ALK rearrangement was 5.6% among EGFR and/or KRAS wild-type/unknown NSCLC population. Pemetrexed, given as a second- or further-line therapy, showed favorable clinical outcomes in ALK-positive NSCLC patients.
Lung cancer (Amsterdam, Netherlands) 10/2012; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Secretory, clear cell, and rhabdoid meningiomas are rare variants of meningiomas characterized by unique histologies and behaviors. Extracellular matrix proteins provide a morphologic structure and influence the biologic behavior of tumors. However, the effects of extracellular matrix proteins on morphologies and biologic behaviors of secretory meningioma, clear cell meningioma, and rhabdoid meningioma have not been established. We evaluated the expression of matrix metalloproteinase 2, matrix metalloproteinase 9, galectin-3, fibronectin, and collagen IV in a series of those rare variants of meningioma and verified their clinicopathologic significance. A total 51 cases included 12 secretory meningiomas, 9 clear cell meningiomas, and 30 rhabdoid meningiomas. Extracellular matrix proteins showed different expression patterns according to the histologic subtypes, and messenger RNA levels were well correlated with immunoexpressions. Secretory meningiomas showed high expressions of fibronectin and galectin-3. Clear cell meningiomas showed high expression of matrix metalloproteinase 2, matrix metalloproteinase 9, and collagen IV. Rhabdoid meningiomas showed high expressions of matrix metalloproteinase 9, galectin-3, and fibronectin. Clinically, high expression of matrix metalloproteinase 9 was associated with tumor recurrence (P < .001) and local invasion at the time of diagnosis (P = .018) among the extracellular matrix-related proteins, and was also associated with shorter recurrence-free survival (P = .025) in the patients with rhabdoid meningioma. In conclusion, the differential expressions of extracellular matrix-related genes according to the histologic subtypes appear to be involved in biologic behavior and clinical outcome, and high matrix metalloproteinase 9 expression is associated with recurrences in rhabdoid meningiomas.
[Show abstract][Hide abstract] ABSTRACT: Malignant peripheral nerve-sheath tumors (MPNSTs) are rare, poorly defined spindle cell sarcomas, and they are accompanied by heterologous elements in some cases. Among them, a fibroblastic element is one of the rarest and has been mentioned in some organs in several publications, but not in the orbit. The authors report a case of fibroblastic low-grade MPNSTs in the orbit. The mass was removed surgically, and the patient has been under close observation without evidence of disease recurrence for 2 years.
Ophthalmic plastic and reconstructive surgery 12/2011; 28(4):e97-8. · 0.69 Impact Factor