Hiroko Furumoto

Epidermal Growth Factor Receptor Overexpression and Genetic Aberrations in Metastatic Squamous-Cell Carcinoma of the Skin

Background: Cutaneous squamous-cell carcinoma (SCC) sometimes causes lymph node metastasis and results in poor prognosis. However, little is known about cytogenetic alterations underlying tumor progression or metastasis. The aim of the present study was to investigate the genetic aberrations and expression of epidermal growth factor receptor (EGFR) in metastatic SCC of the skin. Methods: We undertook comparative genomic hybridization (CGH) analysis of 4 specimens which were obtained from a case of cutaneous SCC, including the primary lesion and 3 lymph nodes of the metastatic lesion. Results: Only one amplified locus (7p12–13) was detected in any metastatic lymph node, in which the EGFR gene is located. Therefore, we applied immunohistochemistry for EGFR to 5 cases of metastatic SCC including the case analyzed using CGH and 4 other cases (5 primary and 5 metastatic lesions). EGFR was expressed in 4 of 5 cases (both primary and metastatic lesions, including the case analyzed using CGH), and the staining patterns of primary and metastatic lesions were different. The primary tumors were focally weakly positive for immunostaining (+), whereas the 4 metastases were diffusely and strongly positive (+++). Conclusions: Our findings suggest that the clone with EGFR expression might selectively metastasize in some cutaneous SCCs. The existence of an EGFR-negative case reveals that EGFR expression is not always required for skin carcinogenesis, but expression of EGFR might confer metastatic potential of cutaneous SCCs.

Overexpression of p53 protein associated with proliferative activity as evaluated by Ki-67 immunostaining in well-differentiated squamous cell carcinoma of the skin

BACKGROUND Overexpression of p53 protein has been demonstrated in a variety of human malignant tumors, and its role in oncogenesis and tumor progression is thought to be important. Recently, some reports have suggested that p53 overexpression might be an indicator of immaturity or proliferative activity of cells in cutaneous lesions. OBJECTIVE The aim of the present study was to clarify the relationship between overexpression of p53 protein and the proliferative activity evaluated by Ki-67 immunostaining in well-differentiated squamous cell carcinoma (SCC) of the skin. METHODS Sixteen cases of well-differentiated SCC were analyzed by immunohistochemistry for the expression of p53 protein and Ki-67 antigen. RESULTS p53 protein was detected in 12 out of the 16 cases (75%). The percentage of p53-protein-positive tumor cells (DO-7 index) ranged from 0 to 80.4 (mean +/- SD = 33.8 +/- 29.7) and the percentage of Ki-67-antigen-positive tumor cells (MIB-1 index) from 23.4 to 65.1 (mean +/- SD = 42.3 +/- 15.8). Cases with higher DO-7 indices tended to show higher MIB-1 indices and the correlation was statistically significant. CONCLUSION Overexpression of the p53 protein seems to be a useful indicator of proliferative activity in cutaneous SCC.

Food-Dependent Exercise-Induced Anaphylaxis Occurring Only in Winter

The syndrome of exercise-induced anaphylaxis represents a distinct form of physical allergy [1, 2]. The intake of particular foods or acetylsalicylic acid and certain weather conditions are possible cofactors [1, 3–5]. In particular, food-dependent exercise-induced anaphylaxis (FDEIA) has been recognized with increasing frequency in recent years. We describe a 13-year-old Japanese girl with FDEIA. Our patient had a 6-year history of urticaria and angioedema associated with exercise after ingestion of wheat-containing foods such as bread and spaghetti, only in winter. The frequency had become higher year by year. The attack often occurred after 10–40 min of outdoor exercise. No other foods induced the symptoms, even after exercise. An allergy prick test was positive for wheat antigen. A cold test with ice cubes was negative. On the basis of this history, the patient received a diagnosis of FDEIA caused by wheat. In order to confirm the diagnosis and to evaluate the effect of inductive factors, provocation tests were performed after admission to our hospital. The attack developed after 15–20 min of outdoor jogging (the temperature was about 10°C) after taking wheat bread, but not by indoor exercise (about 20°C). The severity of the attack was independent of the amount of foods. Although the pathomechanism of FDEIA is still unclear, some causal factors (such as aspirin, infectious diseases, high temperature and high humidity) have been identified [6–9]. In our case, ‘cold’ seems to be a cofactor. Ashida et al. [6] described FDEIA caused by shrimp, which occurred only in winter, and Okano et al. [10] also reported a case of ‘cold-induced’ FDEIA. In these cases, cold is a triggering factor for FDEIA. In general, exercise-induced anaphylaxis is considered to be related to heat rather than cold [3, 5]. ‘Cold-related FDEIA’ might be a distinct disease from ‘ordinary FDEIA’.

Successful Treatment of Vitiligo with a Sex Steroid‐Thyroid Hormone Mixture

Four patients with generalized vitiligo were successfully treated by oral administration of a sex steroid‐thyroid hormone (Metharmon‐F®, 2 tablets daily). Histopathologically, the repigmented skin showed increased numbers of melanocytes and melanin granules in the keratinocytes.

Association of apolipoprotein allele ε2 with psoriasis vulgaris in Japanese population

Abstract We studied phenotypic variations of apolipoprotein E (apoE) and the corresponding allele frequencies in 100 Japanese patients with psoriasis vulgaris (PV). The phenotypes of apoE were examined using analytical isoelectric focusing followed by immunoblotting with goat anti-apoE antibody and alkaline phosphatase-conjugated rabbit antigoat IgG. The phenotypic frequency of apoE3/2 in PV was significantly higher than in healthy controls, and this elevation was associated with an increased frequency of the ε2 allele. Therefore, it is suggested that the apoE molecule plays an important role in the development of PV.

Proteomic profiling of differential display analysis for human oral squamous cell carcinoma: 14-3-3 σ Protein is upregulated in human oral squamous cell carcinoma and dependent on the differentiation level

Oral squamous cell carcinoma (OSCC) has an absolute majority of all oral cancer. We used proteomic technology to analyze the protein expression profile in OSCC tissues and accompanying surrounding normal tissues in four oral locations (buccal mucosa, gingival mucosa, oral floor, and tongue). Ten protein spots were overexpressed more strongly in cancer tissues than normal ones, and were identified as proliferating cell nuclear antigen, 14‐3‐3 ε, 14‐3‐3 σ, proteasome subunit α type 5, translationally controlled tumor protein, eukaryotic translation initiation factor 3 subunit, macrophage capping protein, and mitochondrial isocitrate dehydrogenase subunit α. Macrophage capping protein and mitochondrial isocitrate dehydrogenase subunit α had two spots. Especially, we focused on 14‐3‐3 σ protein, one of the eight identified proteins, and assessed its expression level in four oral locations of OSCC by using differential display methods. The expression level of 14‐3‐3 σ protein was upregulated in four locations of oral cavity. Eight proteins which we identified in this study may play an important role in OSCC carcinogenesis and progression and could be used as diagnostic biomarkers of OSCC.

Disseminated subcutaneous Nocardia farcinica abscesses in a nephrotic syndrome patient.

We describe an unusual case of disseminated subcutaneous abscesses caused by Nocardia farcinica in a 49-year-old man with nephrotic syndrome. He had received systemic corticosteroid therapy for 5 months. He developed a submandibular abscess associated with sialoadenitis on the right submaxillary gland. Magnetic resonance imaging revealed connection between the submandibular abscess and the right submaxillary gland. The subcutaneous abscess spread from the submandibular triangle to the left axillary region, the left upper arm, the left hypochondriac region, the left scapular region, the right epigastric region, and the bilateral legs. A chest radiograph and computed tomograms of the chest and the brain did not reveal any pathologic changes. The patient was successfully treated by surgical drainage of the abscesses and by oral administration of minocycline.

Nonclostridial gas gangrene due to Streptococcus anginosus in a diabetic patient

Streptococcus anginosus was recently identified as a distinct species from the other members of Streptococcus milleri group (Streptococcus constellatus, Streptococcus intermedius). We report a rare case of nonclostridial gas gangrene caused by S. anginosus. A 62-year-old diabetic woman was admitted with gas gangrene of the perineal area. She had been taking her oral hypoglycemia medication regularly for 10 years, but the diabetes was inadequately controlled. She was treated with surgical debridement of the necrotic tissue, insulin injection, and antibiotic therapy, and had a satisfactory clinical course.

A new type of protein chip to detect hepatocellular carcinoma-related autoimmune antibodies in the sera of hepatitis C virus-positive patients

BackgroundWe report here a new type of protein chip to detect antibodies in sera. This chip method was used to a prototype created to detect hepatocellular carcinoma (HCC) -related autoantibodies in the sera of hepatitis C virus (HCV) infected individuals.ResultsFive cysteine-tagged (Cys-tag) and green fluorescent protein (GFP)-fused recombinant heat shock protein 70 (HSP70), superoxide dismutase 2 (SOD2), and peroxiredoxin 6 (PRDX6), were spotted and immobilized on maleimide-incorporated diamond-like carbon (DLC) substrates. The antibodies in diluted sera were trapped by these proteins at each spot on the chip, and visualized by a fluorescence-conjugated anti-human IgG. The total immobilized protein level of each spot was detected with anti-GFP mouse IgG and a fluorescence-conjugated secondary anti-mouse IgG. The ratio between the two fluorescence intensities was used to quantify autoantibody levels in each serum sample. Heat treatment of the chip in a solution of denaturing and reducing agents, before serum-incubation, improved autoantibody detection. We tested serum samples from healthy individuals and HCC patients using the chips. The HSP70 autoantibodies were found at high levels in sera from HCV-positive HCC patients, but not in HCV-negative sera.ConclusionThis protein chip system may have useful properties to capture a specific set of antibodies for predicting the onset of particular cancers such as HCC in HCV-infected individuals.

Profound skin infection with bone involvement due to Nocardia asteroides in a patient with myelodysplastic syndrome

To the Editor: A 81-year-old woman had a cutaneous ulcer with induration and associated satellite lesions on the dorsal aspect of her right foot (Fig. 1a). She had a past history of a burn on the region two years earlier. Magnetic resonance imaging (MRI) showed that the lesion invaded the metatarsal and cuneiform bones (Fig. 1b). Histopathological examination showed abscesses with granulomatous changes containing polymorphonuclear leukocytes, lymphocytes, and plasma cells. Pus obtained from the lesions yielded numerous colonies on Sabouraud dextrose agar and blood agar (Fig. 2) after 7–14 days of incubation at 37°C. The organism was identified as Nocardia asteroides by its growth characteristics and biochemical tests. A chest X-ray examination revealed no pathological changes. The laboratory values were hematocrit 33.2%, red blood cells 3760,000/μl, hemoglobin 11.2 g/dl, white blood cells 3,200/μl, neutrophils 61%, lymphocytes 37%, monocytes 2% and platelets 31,000/μl. A bone marrow aspiration test proved her to have been a myelodysplastic syndrome (MDS) patient. Based upon an in vitro susceptibility test, she was treated with various types of antibiotics over a year, including minocycline (150 mg/day), norfloxacine (300 mg/day), and levofloxacine (300 mg/day), but the treatment failed. We finally tried oral faropenem 600 mg/day with a good clinical response. We continued this therapy for 10 months, and no recurrence has been observed. Nocardiosis is usually an opportunistic infection caused by an aerobic actinomycete, Nocardia, which is acquired from the environment by inhalation and rarely by direct inoculation into the skin. Cutaneous nocardiosis can be divided into four types: 1) mycetoma, 2) lymphocutaneous infection, 3) superficial skin infections such as cellulitis, abscesses, ulcers, or granulomas, and 4) disseminated infection with cutaneous involvement (1, 2). Primary cutaneous nocardiosis, which is usually caused by N. brasiliensis, frequenctly occurs on the leg or the hand of farmers. N. asteroides is an organism that usually infects the pulmonary system and rarely causes cuThe Journal of Dermatology Vol. 28: 582–583, 2001