KRAS and PIK3CA mutations in colorectal adenocarcinomas correlate with aggressive histological features and behavior.

Tumor budding (TB) in colorectal carcinoma (CRC) is related to epithelial-mesenchymal transition and has been recently characterized as an indicator of poor prognosis along with lymphovascular tumor emboli, perineural invasion, and an infiltrative growth pattern. Mutations in the genes of the Ras-mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase pathways are associated with epithelial-mesenchymal transition and an aggressive CRC phenotype and have been used in patient stratification for anti-epidermal growth factor receptor therapies; however, the impact of these mutations on CRC morphology and behavior remains unclear. In this study, using a multigene panel, we detected KRAS, NRAS, BRAF, PIK3CA, TP53, and POLE mutations in 90 CRCs and investigated their associations with clinicopathological parameters, including TB. Our results showed that 21 of 34 tumors with high-grade TB had KRAS mutations (P=.001) and KRAS G12D and PIK3CA exon 9 variants were significantly associated with high-grade TB (P=.002 and .006, respectively); furthermore, tumors with KRAS mutations in exons 3 and 4 tended to have lymphovascular tumor emboli and perineural invasion (P=.044 and .049, respectively). PIK3CA exon 9 mutations indicated a tendency for shorter disease-free survival (P=.030), whereas BRAF mutations were associated with extracellular mucin deposition (P=.016). Our study revealed a correlation of KRAS mutations with high-grade TB, an association of certain KRAS and PIK3CA variants with aggressive clinicopathological features, as well as a possible relationship between BRAF mutations and mucin production in CRC.

A case report of spindle cell myoepithelioma with extensive lipomatous metaplasia and thick collagen bundles in the submandibular gland.

Spindle cell myoepithelioma with extensive lipomatous metaplasia and thick collagen bundles has not yet been described, and there are no published reports on its cytological appearance in fine-needle aspiration (FNA). A 49-year-old man presented with a painless mass in the right submandibular area that had been gradually enlarging for a period of 5 years. The cytologic smears showed fascicles of cohesive spindle cells as well as individual bland cells with bipolar naked nuclei in a fibrillary background. Brightly eosinophilic bundles were intermingled with spindle cells and fat-like vacuoles. The FNA results were suggestive of neurogenic tumor. Patient underwent submandibular gland resection. Grossly, the cut surface showed a well-encapsulated, yellowish-white, soft, elastic mass, measuring 2.8 × 1.9 × 1.5 cm. The tumor consisted of uniform bland spindle cells arranged in short fascicles admixed with adipocyte-like cells and transversing thick collagen bundles, which demonstrated immunoreactivity for myoepithelial markers and ultrastructural features characteristic of myoepithelial cells, suggesting the presence of lipomatous metaplasia. The FNA cytology of spindle cell myoepithelioma with extensive lipometaplasia mimicked that of neurogenic tumor or lipomatous mesenchymal tumor. This case represents the first description of submandibular gland myoepithelioma with lipometaplasia, which is characterized by the coexistence of spindle cells, collagen bundles, and fat-like vacuoles in a fibrillary background. Diagn. Cytopathol. 2016;44:764-769. © 2016 Wiley Periodicals, Inc.

Cribriform-morular variant of papillary thyroid carcinoma: a study of 3 cases featuring the PIK3CA mutation.

The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is an unusual neoplasm with a considerably important association with familial adenomatous polyposis in young women, characterized by a peculiar histologic morphology with mixed cribriform, papillary, solid, tall columnar, and morular patterns. However, it can also occur sporadically. The molecular pathogenesis of sporadic CMV-PTC is not completely understood. We report cases of 3 patients with sporadic CMV-PTC with PIK3CA mutations. Using sequencing analyses and immunohistochemistry, we examined KRAS, BRAF, PIK3CA, and CTNNB1 mutations and related proteins, including ß-catenin, PTEN, CD10, estrogen receptor, progesterone receptor, cytokeratin 19, and cyclin D1 in 3 CMV-PTCs. The 3 patients were teenaged girls. The tumors were solitary and encapsulated without cervical lymph node metastasis. They showed no recurrence for more than 6 years after the operation. Three tumors were diffusely positive for ß-catenin, cyclin D1, and PTEN. The biphasic immunohistochemical patterns between the morular and nonmorular components were identified; the nonmorular components were positive for estrogen receptor, progesterone receptor, and cytokeratin 19, whereas the morular components showed CD10 positivity. All tumors harbored the same mutation in exon 9, codon 545 of the PIK3CA gene (p.E545A), whereas the KRAS, BRAF, and CTNNB1 mutations were not detected. This is the first study identifying the PIK3CA mutation specifically in sporadic CMV-PTC. The presence of the PIK3CA mutation and the wild-type KRAS, BRAF, CTNNB1 genes, and the intact PTEN expression in 3 sporadic CMV-PTCs may suggest the possible contribution of the PIK3CA mutation in its tumorigenesis.

Comparison of HER2 gene amplification and KRAS alteration in eyelid sebaceous carcinomas with that in other eyelid tumors.

Eyelid sebaceous carcinoma (SC) represents a highly aggressive malignancy. Despite the poor prognosis, genetic alterations as potential molecular targets are not available. KRAS mutation and HER2 gene amplification may be candidates related to their genetic alterations. We examined the HER2 and KRAS alteration status in eyelid SCs and compared it with that in other eyelid tumors. The controversial topics of the human papillomavirus (HPV) and p16 expression were also investigated. HER2 amplification was determined by silver in situ hybridization, while immunohistochemistry was performed to study protein expressions in 14 SCs and controls, including 23 other eyelid malignancies and 14 benign tumors. Peptide nucleic acid-mediated PCR clamping and direct sequencing were used to detect KRAS mutations. HER2 protein overexpression was observed in 85.7% (12/14) of the SCs, of which two-thirds showed HER2 gene amplification. HER2 protein overexpression and HER2 amplification were found more frequently in eyelid SCs than in other eyelid tumors. All SCs harbored wild type KRAS genes. No HPV infections were identified in the SCs. Nevertheless, p16 overexpression was found in 71.4% (10/14) of SCs, irrespective of the status of HPV infection. Furthermore, p16 overexpression in eyelid SCs was also significantly higher than that in other eyelid tumors. HER2 protein overexpression, HER2 gene amplifications, and wild type KRAS genes are common in eyelid SCs. HER2 gene amplification may represent potential therapeutic targets for the treatment of eyelid SCs.

Low frequency of KRAS mutation in pancreatic ductal adenocarcinomas in Korean patients and its prognostic value.

OBJECTIVES: Low prevalence and prognostic relevance of KRAS mutations in Korean pancreatic ductal adenocarcinomas (PDACs) need to be validated with sensitive detection method. METHODS: Peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping was used to precisely detect KRAS mutation in 72 paraffinized tumor samples and was validated by pancreatic cell lines to compare the efficiency of direct sequencing. RESULTS: The PNA-mediated PCR clamping detected mutant allele proportions of as low as 0.5% against a background of wild-type DNA and was 20-fold more sensitive than direct sequencing through the validation of pancreatic cell lines. Peptide nucleic acid-mediated PCR clamping detected KRAS mutations in 47.2% of 72 PDACs. Low tumor cellularity and low PCR amplification efficiency led to be undetected or failed by direct sequencing in pancreatic paraffinized samples.KRAS mutations were an independent worse prognostic factor predicting a reduced progression-free survival rate in the postoperative chemotherapy group. CONCLUSIONS: Peptide nucleic acid clamp real-time PCR was a sensitive method for detecting KRAS status in paraffinized PDAC samples. We identified a low KRAS mutation rate among the Korean PDAC patients using PNA clamp real-time PCR, potentially implicating epidemiological characteristics. The low KRAS mutation rate and its prognostic role may suggest the further survival benefit in Korean PDAC patients.

Frequent hepatocyte growth factor overexpression and low frequency of c-Met gene amplification in human papillomavirus-negative tonsillar squamous cell carcinoma and their prognostic significances.

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 2 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 2 were also independent prognostic factors for progression-free survival (P = .023 and P = .002, respectively). In HPV-positive TSCC, heavy alcohol consumption and advanced primary tumor category were predictive of progression-free survival, 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.

Rabies post-exposure prophylaxis of overseas travelers in the international travel clinic of the national medical center from 2006 to 2012, Korea.

BACKGROUND: Rabies is an acute fatal viral disease generally transmitted from infected animals to humans through bites. It is distributed worldwide. The number of Korean people traveling to rabies-endemic countries and being bitten by infected animals has been increasing recently. Therefore, we investigated international travelers who received rabies post-exposure prophylaxis (PEP) at the National Medical Center (NMC) and compared the data with those of other clinics. MATERIALS AND METHODS: This study was a retrospective review of 106 patients who visited the International Travel Clinic of the NMC and received rabies PEP between July 2006 and December 2012. During that period, we used the Essen intramuscular regimen protocol. Complete rabies PEP was defined as 5 doses of rabies vaccination with or without rabies immunoglobulin (RIG) administration according to the World Health Organization guidelines. RESULTS: A total 106 cases documented within the period of 6 years were selected, including 10 children younger than 15 years and 96 older than 15 years. The mean age of the patients who received PEP was 33.4 years. Of the patients, 53 were male and another 53 were female. Most of the exposures occurred in Southeast Asia, predominantly from dog bites (71, 66.9%). The lower extremities were the most frequent site of exposure (37, 34.9%). All the patients began receiving rabies vaccination for prophylaxis after exposure, and 51 received rabies vaccination with RIG. Meanwhile, 74 cases (69.8%) initiated rabies vaccination overseas, but only 10 of them received RIG while overseas; the remaining 32 (30.2%) initiated rabies vaccination after returning to Korea. Within 7 days, all the children and 74 adults received their first rabies vaccination. Six adults initiated first rabies vaccination after 1 week. Eleven of the 106 patients stopped PEP before 5 doses, among whom 4 (1 child and 3 adults) discontinued vaccination after confirming that the biting animal remained healthy throughout 10 days of observation. None of the patients had been previously vaccinated against rabies. CONCLUSIONS: Most of the overseas travelers who visited our clinic after being bitten by suspected rabid animals received appropriate rabies PEP. However, the interval between exposure and first rabies vaccination was often delayed. Tourists who plan to travel in rabies enzootic regions need to be aware that prompt initiation of PEP is important to reduce the risk for developing human rabies.

P2X7 Receptor Expression in Coexistence of Papillary Thyroid Carcinoma with Hashimoto's Thyroiditis.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Histopathologic predictors of lymph node metastasis and prognosis in tonsillar squamous cell carcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

TWIST1 promoter methylation is associated with prognosis in tonsillar squamous cell carcinoma.

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.

E2F1 expression predicts outcome in Korean women who undergo surgery for breast carcinoma.

BACKGROUND: The transcriptional factors E2F1 and E2F2 have been reported to be associated with improved chemosensitivity in various cancers. We aimed to investigate whether E2F1 and E2F2 can be used as predictors of chemosensitivity in hormone-receptor-negative breast cancers (HRNBCs), which are common in Korean women. METHODS: A total of 183 patients with primary breast cancer who had undergone surgical resection were evaluated on the basis of hormonal status, age, histological subtype and grade, tumor size, lymph node metastasis, and stage. The immunohistochemical expressions of E2F1 and E2F2 were analyzed for these histopathological data and patient survival. RESULTS: E2F1 expression was associated with low histological grade (grade 1) and larger tumor size (>2 cm), while E2F2 expression was correlated only with large tumor size (>2 cm). The E2F1-positive group had less tumor recurrences, lymph node metastases during follow-up, and distant metastases than the E2F1-negative group; E2F1 expression was found to be an independent predictive factor of more favorable survival among HRNBC patients on univariate and multivariate analyses, but E2F2 expression was not. CONCLUSIONS: E2F1 may be a potential prognostic and predictive factor for clinical outcome and therapeutic results following adjuvant chemotherapy in HRNBC patients.

Comparison of tissue microarray and full section in immunohistochemistry of gastrointestinal stromal tumors.

The aim of the present study was to compare the efficiency of tissue microarray (TMA) results using immunohistochemistry markers applied to a variety of core sizes and full sections of gastrointestinal stromal tumors (GIST) using performance measures such as core loss rate and concordance rate. Six primary antibody markers (c-Kit, CD34, smooth muscle actin (SMA), S-100, p53, and Ki-67) were used with the TMA technique to analyze 0.6 mm, 2 mm, and 3 mm punch cores of GIST samples from 67 patients. No statistical association was found between core size and loss rate (P= 0.512). TMA results for the 0.6 mm, 2 mm, and 3 mm core showed that all core sizes could statistically significantly reflect full sections with regard to c-Kit, SMA, and S-100 antibodies, but that the 3 mm core section was the most representative except for CD34. With regard to p53 and Ki-67 staining, the 0.6 mm core section was not representative, but the 2 mm and 3 mm core sections could statistically significantly represent full section results. Among them, the 3 mm core section was more accurate than the 2 mm core section. Use of a single 3 mm core size in TMA is suitable for evaluating large numbers of protein and nuclear stains with regard to immunohistochemistry for GIST.

Bowel loop in an ovarian tumor: grossly visible, completely developed intestinal loop in mature cystic teratoma of malignant mixed germ cell tumor.

Although a gastrointestinal-type epithelium is observed in 7-13% of mature cystic teratoma cases, the occurrence of a grossly visible, organized gastrointestinal loop formation is very rare. Presented here is the case of a 14-year-old girl with malignant mixed germ cell tumor in the ovaries. In her left ovary a grossly visible, intestinal loop, 9 cm long, with hanging mesentery attached to the cystic wall of a mature cystic teratoma associated with a yolk sac tumor was observed, and in her right ovary another mature cystic teratoma was observed. Microscopy of the intestinal loop indicated a well-organized, intact layer of small intestinal wall. The yolk sac tumor predominantly had a poly-vitelline pattern. Previously, gastrointestinal wall or epithelium that was identified on microscopy has been reported. To the authors' knowledge this is the first case report of the formation of a grossly visible, completely developed intestinal loop in a malignant mixed germ cell tumor.

High mobility group HMGI(Y) protein expression in head and neck squamous cell carcinoma.

CONCLUSION: We conclude that increased expression level of the high mobility group I (HMGI(Y)) is closely associated with malignant transformation in head and neck squamous cell carcinomas (HNSCCs), and the measurement of HMGI(Y) levels in HNSCCs may be useful as a prognostic marker. OBJECTIVES: To investigate whether HMGI overexpression is observed in HNSCCs, and its value as a prognostic marker in HNSCCs. MATERIALS AND METHODS: HMGI(Y) expression was determined at the protein level by immunohistochemisty using a HMGI(Y)-specific antibody and RT-PCR in 10 surgically resected specimens of non-neoplastic tissue (normal palatal tissue) and 40 HNSCCs. We also evaluated the association of HMGI(Y) overexpression within clinicopathologic parameters, i.e. clinical stage, pathologic grade, status of cervical lymph node metastasis, recurrence rate. RESULTS: Expression of HMGI(Y) by immunohistochemical staining was observed in 35 of 40 (87.5%) HNSCC samples, whereas normal mucosa and/or the mucosa adjacent to the tumor tissue showed negative or weakly positive staining (p<0.05). Semi-quantification of HMGI(Y) by RT-PCR was 2.98+/-2.24 in cancer and 0.47+/-0.25 in normal tissue (p<0.001). High expression of HMGI(Y) was observed in recurrent cases, compared with non-recurrent cases (p<0.05). However, no significant correlation was observed between the levels of HMGI(Y) expression and other clinical factors such as clinical stage, pathologic grade, and status of cervical lymph node metastasis.

Surface and chemical properties of surface-modified UHMWPE powder and mechanical and thermal properties of its impregnated PMMA bone cement, IV: effect of MMA/accelerator on the surface modification of UHMWPE powder.

In our previous study, we manufactured a reinforced poly(methylmethacrylate) (PMMA) bone cement with 3 wt% of the surface-modified ultra high molecular weight polyethylene (UHMWPE) powder to improve its poor mechanical and thermal properties resulting from unreacted methylmethacrylate (MMA), the generation of bubble and shrinkage, and high curing temperature. In the present study, the effect of ratios of MMA and N,N'-dimethyl-p-toluidine (DMPT) solutions in redox polymerization system was investigated for the surface modification of UHMWPE powder. We characterized physical and chemical properties of surface-modified UHMWPE powder and reinforced bone cements by a scanning electron microscope, ultimate tensile strength (UTS) and curing temperature (Tmax). It was found that UTSs (41.3-51.3 MPa) of the reinforced PMMA bone cements were similar to those (44.5 MPa) of conventional PMMA bone cement (control), as well as significantly higher (P < 0.05) than those (33.8 MPa) of 3 wt% unmodified UHMWPE powder-impregnated bone cement. In particular, the UTS of redox polymerization system using MMA/DMPT solution was better than that of radical system using MMA/xylene solution. Also, Tmax of the reinforced PMMA bone cements decreased from 103 to 72-84 degrees C. From these results, we confirmed that the surface-modified UHMWPE powder can be used as reinforcing agent to improve the mechanical and thermal properties of conventional PMMA bone cement.

Imipenem-resistant Achromobacter xylosoxidans carrying blaVIM-2-containing class 1 integron.

We characterized seven isolates of imipenem-resistant Achromobacter xylosoxidans that were isolated from patients hospitalized in the intensive care unit at a tertiary hospital in Korea during 2001 to 2003. From the analysis with an isoelectric focusing, polymerase chain reaction, and sequencing methods, all isolates were found to produce VIM-2, OXA-30, and chromosomal AmpC beta-lactamase with a pI of 8.4. They showed a similar antibiogram, which were resistant to all tested aminoglycosides as well as beta-lactams including imipenem (16-32 mg/L) and aztreonam (128 mg/L), and a same DNA fingerprinting pattern by random amplified polymorphic DNA analysis, suggesting that these originated from a single clone. From the analysis of integron structure carried by an isolate of A. xylosoxidans CBU1760, bla(VIM-2) was found to be part of a gene cassette carried on a class 1 integron (3.4 kb) containing three aacA4 gene cassettes. This is the first report of bla(VIM-2) in A. xylosoxidans.

Expression of maspin is associated with the intestinal type of gastric adenocarcinoma.

PURPOSE: Maspin is known as a tumor suppressor gene, but its significance has been questioned in various human cancers. The aim of this study was to investigate the expression pattern of Maspin in human gastric adenocarcinomas and its possible correlation with clinicopathological findings. MATERIALS AND METHODS: The expression of Maspin mRNA was measured by nested RT-PCR using 60 frozen adenocarcinomas of the stomach and 31 noncancerous tissues from the proximal resection margin. Immunohistochemical study for Maspin protein expression was carried out using 62 paraffin-embedded tissues, composed of both cancer and noncancerous tissues. RESULTS: Maspin mRNA expression was detected in 80.0% (48 of 60) of the gastric adenocarcinomas, but in only 22.6% (7 of 31) of the normal gastric mucosa (p<0.001). The positive rate of Maspin protein expression was higher in the adenocarcinomas than the normal tissues (62.9% vs. 27.4%, p<0.05). In addition, the intestinal type of tumors showed significantly higher expression levels compared to the diffuse type of tumors (81.5% vs. 48.6%, p<0.05). CONCLUSION: Our results suggest that Maspin is frequently expressed in human gastric cancers, and its expression might be associated with tumorigenesis of the intestinal type of gastric cancer.

Expression profiles of p63, p53, survivin, and hTERT in skin tumors.

BACKGROUND: p63 is a p53 homolog and a marker expressed in replicating keratinocytes. Survivin is a recently characterized inhibitor of apoptosis protein that is abundantly expressed in most solid and hematologic malignancies. Telomerase reverse transcriptase (TERT) is the major determinant of human telomerase activity, and its expression is indicative of unlimited replication. We herein evaluated the expression profiles of p63, p53, survivin, and hTERT in usual skin cancers, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) and putative preneoplastic epidermal lesions, including actinic keratosis (AK), Bowen's disease, and porokeratosis. METHODS: Immunohistochemistry using antibodies against p63, p53, survivin, and hTERT was performed. Semi-quantitative evaluation (-, +, 2+, 3+) was carried out. RESULTS: BCCs showed diffuse p63 expression and SCCs heterogeneous p63 expression with negativity in terminally differentiated squamous cells. All preneoplastic epidermal lesions showed p63 expression in all cell layers. p53 was found in seven of 10 cases of BCCs, all 10 cases of SCCs, and nine of 10 cases of Bowen's disease. AK and porokeratosis revealed focal to moderate p53 expression. Survivin was found in eight of 10 cases of SCCs and eight of 10 cases of Bowen's disease. Six of 10 cases of BCCs revealed weak survivin positivity. AK and porokeratosis showed survivin expression confined to the basal layer. hTERT expression was found in most cases of skin cancers and preneoplastic lesions. CONCLUSIONS: p63 expression may be a marker of basal/progenitor cells and a diagnostic marker in skin tumors. p63 expression is not related to p53 expression in these tumors. This study points to a putative role of survivin and hTERT in the development of certain skin cancers. In addition, our data support the concept of porokeratosis being a premalignant condition.

Unilateral, multicentric Warthin's tumor mimicking a tumor metastatic to a lymph node. A case report.

BACKGROUND: Warthin's tumor may be associated with false positive diagnoses of malignancy on fine needle aspiration. The most common cause of error is markedly atypical squamous metaplasia mimicking metastatic cystic squamous carcinoma. The common location of Warthin's tumors within periparotid nodes may add to the clinical suspicion of metastasis. We report a case of unilateral, multicentric Warthin's tumor arising in periparotid and intraparotid glands, leading to a strong clinical and cytologic suspicion of malignancy. CASE: A 60-year-old female presented with a 3-month history of several enlarged lymph nodes in the right side of the neck. Fine needle aspiration, performed at the right upper neck lymph node, suggested the possibility of metastatic tumor. On computed tomography and ultrasonography there were 4 nodular lesions in the right retromandibular area and lateral aspect of the neck, 1-1.5 cm in diameter. A thyroid scan revealed diffuse enlargement of the thyroid gland and a nodular lesion in the right lobe. Right thyroid lobectomy and modified radical neck dissection, including right superficial parotidectomy, were performed for evaluation of occult malignancy. Histologically we confirmed that the tumor was a synchronous, multicentric Warthin's tumor arising in the parotid gland and intraparotid and paraparotid lymph nodes. CONCLUSION: Clinicians and pathologists should consider an extraparotid Warthin's tumor in the differential diagnosis of multiple cervical masses.

Expression of osteoprotegerin and RANK ligand in breast cancer bone metastasis.

Bone destruction is primarily mediated by osteoclastic bone resorption, and cancer cells stimulate the formation and activation of osteoclasts next to metastatic foci. Accumulating evidences indicate that receptor activator of NF-kB ligand (RANKL) is the ultimate extracellular mediator that stimulates osteoclast differentiation into mature osteoclasts. In contrast, osteoprotegerin (OPG) inhibits osteoclast development. In order to elucidate a mechanism for cancer-induced osteoclastogenesis, cells from a human breast cancer line, MDA-MB-231, were directly co-cultured with ST2, MC3T3-E1, or with primary mouse calvarial cells. Osteoclast-like cells and tartarate resistant acid phosphatase (TRAP) activities were then quantitated. We examined these cell lines and samples from breast cancer by RT-PCR for the expressions of OPG and RANKL mRNA. Compared to controls, co-culture of MDA-MB-231 cells with stromal or osteoblastic cells induced an increase in number of osteoclasts and TRAP activities. MDA-MB-231 cells alone or breast cancer samples did not express RANKL mRNA. However, co-culture of these cancer cells with stromal or osteoblastic cells induced RANKL mRNA expression and decreased OPG mRNA expression. These experiments demonstrate that direct interactions between breast cancer and stromal or osteoblastic cells induce osteoclastogenesis in vitro through modulating RANKL expression.