Radiomic biomarkers for platinum-refractory head and neck cancer in the era of immunotherapy.

OBJECTIVE: Immune checkpoint inhibitors (ICI) are recommended as the first-line therapy for platinum-refractory head and neck squamous cell carcinoma (HNSCC), a disease with a poor prognosis. However, biomarkers in this situation are rare. The objective was to identify radiomic features-associated biomarkers to guide the prognosis and treatment opinions in the era of ICI. METHODS: A total of 31 platinum-refractory HNSCC patients were retrospectively enrolled. Of these, 65.5% (20/31) received ICI-based therapy and 35.5% (11/31) did not. Radiomic features of the primary site at the onset of recurrent metastatic (R/M) status were extracted. Prognostic and predictive radiomic biomarkers were analysed. RESULTS: The median overall survival from R/M status (R/M OS) was 9.6 months. Grey-level co-occurrence matrix-associated texture features were the most important in identifying the patients with or without 9-month R/M death. A radiomic risk-stratification model was established and equally separated the patients into high-, intermittent- and lower-risk groups (1-year R/M death rate, 100.0% vs. 70.8% vs. 27.1%, p = 0.001). Short-run high grey-level emphasis (SRHGE) was more suitable than programmed death ligand 1 (PD-L1) expression in selecting whether patients received ICI-based therapy. CONCLUSIONS: Radiomic features were effective prognostic and predictive biomarkers. Future studies are warranted.

Clinical effects of dupilumab: A novel treatment for Kimura disease.

BACKGROUND: Kimura disease (KD) is a rare chronic inflammatory disorder involving the Th2 pathway. Although medical treatment with steroids or other immunosuppressants is available, they may cause developmental issues in the pediatric population. Surgical intervention has also been suggested; however, it is associated with high recurrence rates. CASE PRESENTATION: A 14-year-old boy presented with left retroauricular lymph node enlargement at the age of 5 years. At the age of 7 years, he was diagnosed with nephrotic syndrome which subsided after steroid treatment for approximately 6 years. The retroauricular lymph node was surgically excised, and KD was confirmed. However, recurrent enlargement of the left retroauricular and neck lymph nodes occurred after 2 years. Persistently high IgE levels and fluctuating eosinophil counts were observed following steroid treatment. Dupilumab was prescribed because of the difficulty in tapering the steroid dosage. A loading dose of 600 mg was administered, followed by a maintenance dose of 300 mg every 2 weeks. The IgE level decreased after 3 months, and a low eosinophil count was maintained after steroid discontinuation. Follow-up computed tomography revealed a decrease in the size of the lymph nodes with no side effects such as conjunctivitis. CONCLUSION: Traditional treatments have raised developmental concerns in the pediatric population and are associated with high recurrence rates. Dupilumab targets the Th2 pathway and provides effective results, with few adverse effects. Dupilumab may be a therapeutic option for KD and other diseases involving the Th2 pathway.

Adult-Onset Still's Disease following Coronavirus 2 (SARS-CoV-2) Vaccination: A Case Report.

In recent years, during the ravages of COVID-19, a variety of vaccines have been developed and are now on the market. However, although these new vaccines have undergone various trials, there are still many unknown side effects. We report a case of a 30-year-old woman who presented with general weakness, sore throat, generalized skin rashes, symmetrical arthralgia, and persistent fever of up to 40 °C with onset 16 days after receiving the Moderna COVID-19 vaccine. Adult-onset Still's disease (AOSD) was diagnosed according to Yamaguchi's criteria after excluding the feasibility of infectious diseases, autoimmune diseases, and malignancies. In particular, her responses to glucocorticoids and naproxen were significant and inversely proportional to her use of empirical antibiotics in the initial stage of treatment. We studied some similar cases of AOSD, which also considered the adverse effects of COVID-19 vaccination and suggested the immunogenicity and possibility of inflammatory responses related to COVID-19 vaccination.

Plasma Endoglin is Associated with Favorable Outcome for Pemetrexed-Based Therapy in Advanced Non-Small Cell Lung Cancer.

PURPOSE: Pemetrexed-based chemotherapy (Pem-C) is the first-line chemotherapy for advanced non-squamous non-small cell lung cancer (NSCLC). However, limited tumor-associated proteins in blood are available to predict pemetrexed response and/or survival. PATIENTS AND METHODS: Plasma samples from three responders and three nonresponders with stage IIIB-IV NSCLC were collected prior to Pem-C and analyzed using Proteome ProfilerTM Human XL Oncology Array to detect 84 oncology-related proteins. The plasma concentrations of cathepsin S, endoglin (ENG), and matrix metalloproteinases 3 and 9 in 71 patients with advanced NSCLC treated with Pem-C were further measured using enzyme-linked immunosorbent assay based on the remarkable differences in the four proteins between responders and nonresponders in the array results. RESULTS: Pem-C responders had significantly higher ENG levels but not the other three markers than nonresponders (mean ENG level: 27.1 ± 7.4 vs 22.3 ± 6.9, p < 0.01). High ENG concentration was correlated with improved progression-free survival (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.31-0.86, p < 0.01) and overall survival (HR: 0.55, 95% CI: 0.32-0.94, p < 0.05) in patients treated with Pem-C, and the ENG level was an independent factor in our cohort (HR: 0.54, 95% CI: 0.33-0.89, p < 0.05). ENG concentration in Pem-C responders also significantly increased at the time of best response (p < 0.05). CONCLUSION: Cumulatively, this study reveals that ENG is correlated with Pem-C responsiveness in patients, which indicates the potential use of plasma ENG levels as a non-invasive biomarker for pemetrexed-based treatment in patients with non-squamous NSCLC.

The Protective Role of GMI, an Immunomodulatory Protein From Ganoderma microsporum, on 5-Fluorouracil-Induced Oral and Intestinal Mucositis.

5-Fluorouracil (5-FU) is used in the treatment of head and neck cancer patients. However, adverse effects experienced such as mucositis and poor appetite may lead to interruption in chemotherapy. The aim of this study is to evaluate the efficacy of GMI, one fungal immunomodulatory protein found in Ganoderma microsporum, for mucositis induced by 5-FU in a mouse model. Mice were administered 5-FU intraperitoneally for 4 days per cycle for a total of 2 chemotherapy cycles. In addition, mice were pretreated with GMI or phosphate-buffered saline 3 days before 5-FU intraperitoneal injection and daily until day 14. On histological analysis, GMI prevented 5-FU-induced damage to the intestinal mucosa and tongue epithelium. We also demonstrated that GMI enhanced the cytotoxicity of 5-FU in 2 oral cancer cell lines, while GMI could not promote this effect in an oral normal cell. In conclusion, GMI alleviates 5-FU-induced damage and decelerates cell death in normal alimentary tract tissue.

Protective Effects of Morus Root Extract (MRE) Against Lipopolysaccharide-Activated RAW264.7 Cells and CCl4-Induced Mouse Hepatic Damage.

BACKGROUND/AIMS: Inflammation is one of the main contributors to chronic diseases such as cancer. It is of great value to identify the potential activity of various medicinal plants for regulating or blocking uncontrolled chronic inflammation. We investigated whether the root extract of Morus australis possesses antiinflammatory and antioxidative stress potential and hepatic protective activity. METHODS: The microwave-assisted extractionwere was used to prepare the ethanol extract from the dried root of Morus australis (MRE), including polyphenolic and flavonoid contents. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells was examined the anti-inflammatory and anti-oxidative potential of MRE. CCl4-induced mouse hepatic damage were performed to detect the hepatic protective potential in vivo. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. RESULTS: MRE contained approximately 23% phenolic compounds and 3% flavonoids. The major flavonoid component of MRE was morusin. MRE and morusin inhibited lipopolysaccharide-induced production of nitrite and prostaglandin E2 in RAW264.7 cells. MRE and morusin also suppressed the formation of intracellular reactive oxygen species and the expression of iNOS and COX-2. In an in vivo study, a thiobarbituric acid reactive substances assay showed that MRE inhibited CCl4-induced oxidative stress and expression of nitrotyrosine. MRE also decreased CCl4-induced hepatic iNOS and COX-2 expression, as well as CCl4-induced hepatic inflammation and necrosis in mice. CONCLUSION: MRE exhibited antiinflammatory and hepatic protective activity.

Association of Fibroblast Growth Factor Receptor 4 Genetic Polymorphisms With the Development of Uterine Cervical Cancer and Patient Prognosis.

This is the first study to investigate the relationships among fibroblast growth factor receptor 4 (FGFR4) genetic polymorphisms, development of uterine cervical cancer, clinicopathological variables, and patient prognosis in Taiwanese women. Real-time polymerase chain reaction and genotyping were used to detect the genotype frequencies of 4 FGFR4 single-nucleotide polymorphisms (SNPs), rs351855 (C/T, Gly388Arg), rs2011077 (G/A), rs7708357 (G/A), and rs1966265 (Ile10Val), in 138 patients with invasive cancer, 89 with precancerous lesions of uterine cervix, and 335 normal controls. The results showed that there is no significant difference in the frequencies of FGFR4 SNPs rs351855, rs2011077, rs7708357, and 1966265 between women with cervical invasive cancer and normal controls even after controlling for age. However, significant differences existed in the distributions of the FGFR4 genetic polymorphism rs2011077, when mutant homozygotes (AA) were compared using other genotypes (GG/GA) as a reference, as well as rs1966265, when mutant homozygotes (AA) were compared using GG/GA as a reference, between women with cervical precancerous lesions and normal women even after controlling for age. In multivariate analysis, lymph node metastasis was associated with cancer recurrence, and lymph node metastasis and FGFR4 rs351855 were associated with patient survival. In conclusion, our study demonstrated that FGFR4 rs2011077 and rs1966265 are associated with the progression of cervical normal tissues to precancerous lesions in Taiwanese women. Moreover, rs351855 (Gly388Arg) is the only FGFR4 genetic polymorphism that is associated with patient survival.

Impact of microRNA-34a and polymorphism of its target gene CA9 on susceptibility to uterine cervical cancer.

The purposes of this study were to associate the genetic polymorphisms in carbonic anhydrase (CA) 9 with uterine cervical cancer and identify the clinical implications. Three single-nucleotide polymorphisms (SNPs), rs2071676 (+201, G/A), rs3829078 (+1081, A/G), and rs1048638 (+1584, C/A), and an 18-base-pair deletion/insertion (376del393) in CA9 were examined. We used the Boyden chamber assay to evaluate the influence of CA9 on the migration of cervical cancers. Tissue microarrays were used to evaluate CAIX immunoreactivity and determine its clinical significance. The results revealed that the CA9 SNP rs1048638 is the only significant polymorphism that increases the risk of cervical cancer in Taiwanese women. We discovered that the CA9 SNP rs1048638 influences the expression of CA9 through the interaction between the 3'-untranslated region (UTR) of exon 11, where the SNP is located, and miR-34a, and influences the migration of cervical cancer cells. Moreover, we demonstrated that CAIX immunoreactivity is related to the occurrence of cervical cancer, and elevated CAIX immunoreactivity is associated with a more advanced stage. In conclusion, the finding that the CA9 SNP rs1048638 exerts its action through duplexes of the miR-34a and CA9 3'-UTRs and plays a vital role in cervical cancer in Taiwanese women may be applicable to translational medicine.

Upregulation of caveolin-1 by mulberry leaf extract and its major components, chlorogenic acid derivatives, attenuates alcoholic steatohepatitis via inhibition of oxidative stress.

Excessive alcohol uptake exerts hepatocellular toxicity, ultimately leading to multiple liver diseases such as steatohepatitis and liver cirrhosis. Here, we aimed to explore the effects of mulberry leaf extract (MLE) and its major components chlorogenic acid (CGA) and neochlorogenic acid (nCGA) on alcoholic steatohepatitis. We determined the composition of MLE using liquid chromatography-mass spectrometric (LC-MS) analysis, which showed that MLE consisted of mainly chlorogenic acid derivatives and other polyphenols. Next, we utilized a high alcohol-fed mouse model and demonstrated that MLE alleviated alcohol-induced hepatocellular disorders, resulting in lowered hepatic injury markers and lipid accumulation. In addition, MLE reduced lipid peroxidation and meanwhile elevated hepatic superoxide dismutase (SOD). Immunohistochemical (IHC) staining revealed that MLE elevated the expression of caveolin-1 but reduced the expressions of epidermal growth factor receptor (EGFR), signal transducer and activator of transcription (STAT), inducible nitric oxide synthase (iNOS) and receptor interacting protein (RIP) 1/3. Major components of MLE, CGA and nCGA, not only exerted a similar biological activity as MLE but also inhibited alcohol-induced pro-apoptotic signals. Involvement of caveolin-1 in MLE, CGA and nCGA was demonstrated by using specific small inhibitory RNA. In conclusion, MLE and its chlorogenic derivatives CGA and nCGA upregulate caveolin-1 expression and diminish EGFR/STAT3/iNOS signalling, which may contribute to lowered hepatic lipid accumulation and peroxidation and inhibited pro-apoptotic cascades.

Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression.

Apigenin (4',5,7-trihydroxyflavone), a flavonoid commonly found in fruits and vegetables, has anticancer properties in various malignant cancer cells. However, the molecular basis of the anticancer effect remains to be elucidated. In this study, we investigated the cellular mechanisms underlying the induction of cell cycle arrest by apigenin. Our results showed that apigenin at the nonapoptotic induction concentration inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in the MDA-MB-231 breast cancer cell line. Immunoblot analysis indicated that apigenin suppressed the expression of cyclin A, cyclin B, and cyclin-dependent kinase-1 (CDK1), which control the G2-to-M phase transition in the cell cycle. In addition, apigenin upregulated p21WAF1/CIP1 and increased the interaction of p21WAF1/CIP1 with proliferating cell nuclear antigen (PCNA), which inhibits cell cycle progression. Furthermore, apigenin significantly inhibited histone deacetylase (HDAC) activity and induced histone H3 acetylation. The subsequent chromatin immunoprecipitation (ChIP) assay indicated that apigenin increased acetylation of histone H3 in the p21WAF1/CIP1 promoter region, resulting in the increase of p21WAF1/CIP1 transcription. In a tumor xenograft model, apigenin effectively delayed tumor growth. In these apigenin-treated tumors, we also observed reductions in the levels of cyclin A and cyclin B and increases in the levels of p21WAF1/CIP1 and acetylated histone H3. These findings demonstrate for the first time that apigenin can be used in breast cancer prevention and treatment through epigenetic regulation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 434-444, 2017.

Complicated skin and soft tissue infection with Mycobacterium fortuitum following excision of a sebaceous cyst in Taiwan.

Mycobacterium fortuitum group (M. fortuitum), also known as rapidly growing Mycobacteria, can cause pyogenic infections in human beings, most commonly in immunocompromised patients. Herein, we present a 40-year-old immunocompetent male patient who underwent planned excision of a sebaceous cyst in the abdominal wall. He suffered from tender erythematous lesions with purulent discharge around the healing wound that developed 2 weeks after surgery. Gram stain, bacterial and fungal culture results of the wound were negative. A diagnosis of non-tuberculous mycobacteria was made from a wound culture from the area of operative debridement, which was subsequently confirmed to be M. fortuitum group using PCR-restriction fragment length polymorphism analysis of the hsp65 gene. The patient received 4 weeks of parenteral imipenem/cilastatin 500 mg every 6 hours and amikacin 500 mg every 12 hours, plus oral clarithromycin 500 mg twice daily, and the wound recovered completely. He was discharged and followed up regularly at our outpatient clinic, and continued taking oral ciprofloxacin and clarithromycin 500 mg twice daily for 6 months. This case highlights the importance of strict aseptic precautions even during minor procedures, and also the characteristics of M. fortuitum infections in immunocompetent patients, which usually develop as localized postsurgical wound infections. We also share our experience in successfully treating a M. fortuitum complicated skin and soft tissue infection.

Association of single-nucleotide polymorphisms of high-mobility group box 1 with susceptibility and clinicopathological characteristics of uterine cervical neoplasia in Taiwanese women.

To date, no study associated the genetic polymorphisms of high-mobility group box 1 protein (HMGB1) with the development of uterine cervical cancer. We therefore conducted this study to investigate the associations of HMGB1 single-nucleotide polymorphisms (SNPs) with cervical carcinogenesis and clinicopathological characteristics of cancer patients. Five hundred two women, including 112 with invasive cancer, 85 with precancerous lesions of the uterine cervix, and 305 normal controls, were consecutively enrolled into this study. Analysis of HMGB1 SNPs was done by real-time polymerase chain reaction and genotyping. Our results found that the risk of susceptibility to cervical invasive cancer was 1.85 (95 % CI 1.12-3.04; p = 0.016) in women with TC and 1.99 (95 % CI 1.24-3.23; p = 0.005) in women with TC/CC after adjusting for age, using TT as a comparison reference in HMGB1 SNP rs1412125. In rs2249825, the increased risk was also seen for the development of cervical invasive cancer in women with CG [adjusted odds ratio (AOR) 2.04, 95 % CI 1.22-3.40; p = 0.006] or CG/GG (AOR 2.02, 95 % CI 1.22-3.32; p = 0.006) using CC as a comparison reference. An additional integrated in silico analysis confirmed that rs2249825 creates a binding site for v-Myb, which may affect HMGB1 expression. In conclusion, Taiwanese women with TC or TC/CC in HMGB1 SNP rs1412125 as well as CG or CG/GG in rs2249825 were susceptible to the development of cervical invasive cancer.

Moniliformediquinone as a potential therapeutic agent, inactivation of hepatic stellate cell and inhibition of liver fibrosis in vivo.

BACKGROUND: Moniliformediquinone (MFD), a phenanthradiquinone in Dendrobium moniliforme, was synthesized in our laboratory. Beyond its in vitro inhibitory effects on cancer cells, other biological activity of MFD is unknown. The purpose of the present study was to investigate the effects of MFD on hepatic fibrogenesis in vitro and in vivo. METHODS: Hepatic stellate HSC-T6 was cultured. Cell viability assay and western blot analyses were performed. Male ICR mice were evaluated on CCl4-induced hepatotoxicity using both histological examination and immunohistochemical staining. RESULTS: First, in vitro study showed that the synthesized MFD effectively attenuated the expression of transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and type I collagen (COL-1), which modulated the hepatic fibrogenesis. Furthermore, MFD reduced the phosphorylation of p65 NFκB in HSC-T6 cells. In vivo, liver fibrosis was induced by CCl4 twice a week for 10 weeks in mice. The administration of the MFD was started after 1 week of CCl4 thrice-weekly; the MFD significantly reduced plasma aspartate transaminase (AST) and lactose dehydrogenase (LDH) as well as hepatic hydroxy-proline, α-SMA, and COL-1 expression in CCl4-treated mice. Pathological analysis showed that the MFD alleviated CCl4-induced hepatic inflammation, necrosis and fibrosis. These results suggest that MFD possesses therapeutic potential for liver fibrosis. CONCLUSIONS: The synthesized MFD exhibits anti-fibrotic potential by inactivation of HSCs in vitro and decreases mouse hepatic fibrosis in vivo. Further investigation into their clinical therapeutic potential is required.

Antitumor progression potential of morusin suppressing STAT3 and NFκB in human hepatoma SK-Hep1 cells.

Morusin is a prenylated flavonoid that has been isolated from the root bark of the mulberry tree (Morus species, Moraceae), a Chinese traditional medicine. It has been synthesized by our laboratory from commercially available phloroglucinol, and has demonstrated to possess antitumor effects of cell lines including A549, MCF-7, and MDA-MB-231. In this study, at non-cytotoxic concentrations, morusin altered invasive morphology and suppressed cell-matrix adhesion, cell motility and cell invasion in SK-Hep1 cells. Morusin also increased the expression of E-cadherin, an epithelial cell junction protein, decreased the expression of vimentin, a mesecnchymal marker, and α2-, α6-, ß1- integrin, which regulated cancer attachment and migration. In addition, morusin reduced the activity of matrix metalloproteinase-2 and 9 (MMP-2 and MMP-9), which were involved in extracellular matrix (ECM) degradation and promoting cancer cell invasion. Furthermore, morusin suppressed the signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NFκB) signaling pathways, which modulate the protein expression involved in the invasion process. Finally, morusin decreased the lung colonization of the SK-Hep1 cells in the nude mice. These results indicate morusin possesses antitumor progression potential through suppressing STAT3 and NFκB.

A qualitative study comparing the assay performance characteristics between the 2007 and the 2013 American Society for Clinical Oncology and College of American Pathologists HER2 scoring methods in mucinous epithelial ovarian cancer.

The remarkable success of trastuzumab and other newly developed anti-HER2 (human epidermal growth factor receptor 2) therapies in breast, gastric, or gastroesophageal junction cancer patients has supported us to investigate the HER2 status and its possible therapeutic implication in mucinous epithelial ovarian cancer (EOC). However, there is currently no standardization of HER2 scoring criteria in mucinous EOC. In this study, we aimed to compare both the assay performance characteristics of the 2007 and the 2013 American Society for Clinical Oncology and College of American Pathologists scoring methods. Forty-nine tissue microarray samples of mucinous EOC from Asian women were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests using the 2007 and the 2013 criteria, respectively. The overall concordance between IHC and FISH by the 2007 criteria was 97.92 % (kappa = 0.921), and that by the 2013 criteria was 100% (kappa = 1.000). The percentage of Her2 FISH-amplified cases showed an increasing trend significantly through their corresponding HER2 IHC ordinals by the 2007 and the 2013 criteria, respectively (P < 0.001, P < 0.001). After excluding equivocal cases, the specificity (100%) and positive predictive value (100%) were unchanged under either the 2007 or the 2013 criteria. The sensitivity (100%), negative predictive value (NPV) (100%), and accuracy (100%) of HER2 IHC were higher under the 2013 criteria than those (sensitivity 87.5%, NPV 97.6%, and accuracy 97.9%) under the 2007 criteria. Of the total 49 cases, the number (n = 4) of HER2 IHC equivocal results under the 2013 criteria was 4-fold higher than that (n = 1) under the 2007 criteria (8.16% vs 2.04%). Conclusively, if first tested by IHC, the 2013 criteria caused more equivocal HER2 IHC cases to be referred to Her2 FISH testing than the 2007 criteria. That decreased the false-negative rate of HER2 status and increased the detection rates of HER2 positivity in mucinous EOC.

Ethyl acetate extract of Wedelia chinensis inhibits tert-butyl hydroperoxide-induced damage in PC12 cells and D-galactose-induced neuronal cell loss in mice.

BACKGROUND: Wedelia chinensis is traditionally used as a hepatoprotective herb in Taiwan. The aim of this study was to evaluate the neuroprotective potential of W. chinensis. METHODS: An ethyl acetate extract of W. chinensis (EAW) was prepared and analyzed by HPLC. The neuroprotective potential of EAW was assessed by tert-butylhydroperoxide (t-BHP)-induced damage in PC12 cells and D-galactose-induced damage in mouse cortex. RESULTS: EAW exhibited potent radical scavenging property and highly contained luteolin and wedelolactone. EAW decreased t-BHP-induced reactive oxygen species (ROS) accumulation, cytotoxicity and apoptosis in PC12 cells. EAW and its major constituents blocked t-BHP-induced cytochrome C release and Bcl-2 family protein ratio change. EAW and its major constituents increased the endogenous antioxidant capacity evaluated by the binding activity assay of nuclear factor E2-related factor 2 (Nrf2) to antioxidant response element (ARE) and nuclear translocation of Nrf2 respectively in PC12 cells. Finally, EAW inhibited D-galactose-induced lipid peroxidation, apoptosis and neuron loss in the cerebral cortex of mice. CONCLUSION: These results demonstrate that W. chinensis has neuroprotective potential through blocking oxidative stress-induced damage and that luteolin and wedelolactone contribute to the protective action.

Assessing the HER2 status in mucinous epithelial ovarian cancer on the basis of the 2013 ASCO/CAP guideline update.

Her2 gene amplification and protein overexpression are important factors in predicting clinical sensitivity to anti-HER2 monoclonal antibody therapy in breast, gastric, or gastro-esophageal junction cancer patients. The purpose of this study was to evaluate the HER2 status in the mucinous epithelial ovarian cancer (EOC). Adopting the 2013 American Society for Clinical Oncology and the College of American Pathologists guideline update for HER2 testing, 49 tissue microarray samples of mucinous EOC were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests. The prevalence of HER2 positivity in Asian mucinous EOC was 9 of 49 Asian women (18.37%). The overall concordance was 100% between IHC and FISH results. Her2 gene copies before chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal, and positive IHC result categories (P<0.001), as did the Her2 gene copies after chromosome-17 correction (P<0.001). Of the Taiwanese cohort (n=21), HER2 heterogeneity was 4.76% (1/21) in all but 14.26% (1/7) in HER2-positive cancer. In conclusion, we demonstrated that the prevalence of HER2 positivity in both Asian and white women was comparable; complete HER2 concordance existed between IHC and FISH tests for the Her2 gene copies per tumor cell either before or after correction of chromosome-17, and this can be applied as a potentially valuable tool to analyze the HER2 status. Polysomy-17 was absent under the CEP17 cutoff ≥3. The existence of HER2 heterogeneity can be discerned in certain HER2-expressed primary mucinous EOC in Taiwanese women.

Steatocystoma multiplex as initial impression of non-small cell lung cancer with complete response to gefitinib.

Cutaneous metastases are rare and seldom present at the time of first diagnosis of cancer. Data from various studies show that 1-12% of lung cancer patients experience tumor spread to the skin. The scalp, chest, and abdomen are favored sites of skin metastases from lung cancers, but metastases to multiple skin sites in a single patient are rarely reported. We describe a 56-year-old lung adenocarcinoma patient, initially diagnosed with steatocystoma multiplex who responded well to gefitinib treatment. The efficacy of conventional chemotherapy for cutaneous metastases has been limited because of the relatively poor blood supply to the skin. It has been demonstrated that tyrosine kinase inhibitor (TKI), gefitinib, has significant clinical benefit in lung cancer patients with epidermal growth factor receptor (EGFR) mutation even in metastases to the brain. However, the therapeutic response to gefitinib in patients with skin metastases is seldom mentioned in the literature. We report one case of lung adenocarcinoma with multiple skin metastases that were successfully treated with gefitinib.