ABSTRACT
INTRODUCTION: Solitary fibrous tumour (SFT) is a rare mesenchymal tumour with intermediate malignant potential. Although this tumour arises in several sites, prostatic SFT is an extremely rare neoplasm and may prove confusing owing to the lack of clinical experience because of tumour rarity. The diagnosis may be further difficult because SFTs can manifest positive immunoreactivity for CD34 and progesterone receptor, which are known markers of prostatic stromal tumours. Herein, we describe a case of prostatic SFT that was difficult to differentiate from a prostatic stromal tumour of uncertain malignant potential because of positive immunoreactivity to CD34 and progesterone receptor. CASE REPORT: A 40-year-old Japanese man presented with lower abdominal pain. Computed tomography revealed a prostatic mass; furthermore, prostate core needle biopsy revealed proliferating bland spindle cells, without necrosis or prominent mitoses. Tumour cells were positive for CD34 and progesterone receptor on immunohistochemical analysis; thus, a prostatic stromal tumour of uncertain malignant potential was initially suspected. However, as the tumour cells showed positive immunoreactivity for STAT6, the final diagnosis was an SFT of the prostate. The patient underwent tumour resection, and at the 6-month postoperative follow-up, neither local recurrence nor distant metastasis occurred. CONCLUSION: For an accurate diagnosis of an SFT of the prostate, STAT6 immunohistochemistry should be conducted for all mesenchymal tumours of the prostate. When STAT6 immunohistochemical analysis is unfeasible, pathologists should be aware that the morphological and immunohistochemical characteristics of SFT variable from case to case and diagnose with combined analysis of several immunohistochemical markers.
Subject(s)
Biomarkers, Tumor/analysis , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Solitary Fibrous Tumors/diagnosis , Solitary Fibrous Tumors/pathology , Adult , Humans , Male , STAT6 Transcription Factor/biosynthesisABSTRACT
PURPOSE: To verify distress and impact thermometer (DIT) for screening emotional distress in gynecological cancer patients by Hospital Anxiety and Depression Scale total (HADS-T) as gold standard and to assess emotional changes by DIT and HADS-T. METHODS: A prospective study was conducted in newly diagnosed gynecological cancer patients during the peri-treatment period after the cancer diagnosis followed by 6-month. We defined a HADS-T score of ≥11 as being indicative of emotional distress. RESULTS: 117 patients were enrolled between May 1, 2011 and March 31, 2012, and 95 were eligible. The median age was 54 years (range 31-77). (1) From the baseline to 3-month, distress (DIT-D) ≥4 with Impact (DIT-I) ≥2 exhibited sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) of 0.776 [95 % confidential interval (CI) 0.688, 0.850], 0.889 (95 % CI 0.824, 0.954), 0.868 (95 % CI 0.792, 0.949), and 0.808 (95 % CI 0.731, 0.886), respectively. (2) At 6-month, DIT-D ≥2 with DIT-I ≥1 exhibited sensitivity, specificity, PPV and NPV of 0.893 (95 % CI 0.778, 1), 0.825 (95 % CI 0.707, 0.942), 0.781 (95 % CI 0.638, 0.928), and 0.917 (95 % CI 0.826, 1). (3) At 6-month, the HADS-T, DIT-D, and DIT-I scores in individual patients were significantly reduced by a mean of 4.57 (p < 0.0001), 2.34 (p < 0.0001), and 1.10 (p = 0.0031), respectively, compared with those scores of baseline (Student's paired t test), but still remained high. CONCLUSIONS: (1) On acute phase within 3-month setting, DIT; DIT-D ≥4 with DIT-I ≥2, is a reliable cut-off to screen emotional distress among gynecological cancer patients. (2) The patients' moods had improved, but not completely recovered at 6-month after the diagnosis.
Subject(s)
Anxiety/diagnosis , Depression/diagnosis , Genital Neoplasms, Female/psychology , Mood Disorders/diagnosis , Psychometrics/methods , Adult , Aged , Female , Genital Neoplasms, Female/therapy , Humans , Medical Oncology , Middle Aged , Predictive Value of Tests , Prospective StudiesABSTRACT
Ovarian and endometrial cancers diagnosed at advanced stages are often associated with malignant ascites. This study aimed to determine the safety, feasibility and efficacy of intraperitoneal (IP) docetaxel (TXT) for the treatment of ascites. A phase I study, including nine patients, was undertaken to determine the maximum tolerable dose. Efficacy was retrospectively assessed in 18 patients treated with 40-70 mg/m(2) IP TXT between 2005 and 2012. In a phase I study, the dose was safely escalated to a maximum of 70 mg/m(2), at which level no patients had grade -3 haematological adverse events. In a retrospective study of 18 patients, seven had an Eastern Cooperative Oncology Group performance status of 3; 16 had prior paclitaxel administration and two, with doses of 40 and 70 mg/m(2), experienced a serological response and a decrease in paracentesis. Thus, palliative treatment of recurrent OC should be further studied with 40 mg/m(2) among more patients, and 70 mg/m(2) could be evaluated for first-line IP chemotherapy.
Subject(s)
Adenocarcinoma, Clear Cell/drug therapy , Antineoplastic Agents/administration & dosage , Ascites/drug therapy , Genital Neoplasms, Female/drug therapy , Taxoids/administration & dosage , Adenocarcinoma, Clear Cell/complications , Aged , Ascites/etiology , Docetaxel , Feasibility Studies , Female , Genital Neoplasms, Female/complications , Humans , Infusions, Parenteral , Middle Aged , Retrospective Studies , Salvage TherapyABSTRACT
BACKGROUND: We evaluated the methylation patterns of histone H3 lysine 27 (H3K27), H3 lysine 36 (H3K36) and the expression of H3K27 methylase EZH2 in patients with colorectal carcinomas with metachronous liver metastasis to search for biomarkers identifying these patients. METHODS: Double 2-mm core tissue microarrays were made from 54 paraffin-embedded samples of primary colorectal adenocarcinomas and corresponding liver metastases and examined using an immunohistochemical analysis of dimethylation and trimethylation in H3K27, H3K36 and EZH2. Positive tumor cell staining for each histone modification (H-score) was used to classify patients into low- and high-staining groups, which were then examined to identify any correlations between the clinicopathological parameters and the clinical outcomes. RESULTS: The H-scores of H3K27me2 were lower in the liver metastases than in the corresponding primary tumors, while the H-scores of H3K36me2 were higher in the liver metastases than in the corresponding primary tumors (P < 0.001). H3K27me2 in the primary tumors correlated with tumor size (P = 0.016), H3K36me2 in the primary tumors correlated with histological type (P = 0.038), and H3K36me3 in the primary tumors correlated with lymph node metastasis (P = 0.017). In addition, lower levels of H3K27me2 in the primary tumors correlated with poorer survival rates (P = 0.039). The multivariate survival analysis showed that the H3K27me2 status is an independent prognostic factor for colorectal cancer patients (P = 0.047). CONCLUSIONS: Our findings suggest that the methylation level of H3K27me2 detected with immunohistochemistry may be an independent prognostic factor for metachronous liver metastasis of colorectal carcinomas.
Subject(s)
Adenocarcinoma/metabolism , Colorectal Neoplasms/metabolism , Histones/metabolism , Liver Neoplasms/metabolism , Neoplasms, Second Primary/metabolism , Polycomb Repressive Complex 2/metabolism , Adenocarcinoma/enzymology , Adenocarcinoma/genetics , Adenocarcinoma/secondary , Adult , Aged , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Methylation , Enhancer of Zeste Homolog 2 Protein , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Liver Neoplasms/enzymology , Liver Neoplasms/genetics , Liver Neoplasms/secondary , Lysine , Male , Methylation , Middle Aged , Multivariate Analysis , Neoplasms, Second Primary/enzymology , Neoplasms, Second Primary/genetics , Neoplasms, Second Primary/secondary , Prognosis , Retrospective Studies , Risk Factors , Tissue Array AnalysisABSTRACT
BACKGROUND: Inhibitors of the epidermal growth factor (EGFR) signaling pathway have a major role in the treatment of KRAS wild-type colorectal cancer patients. The EGFR pathway has been shown to be activated in gastric cancer (GC). However, published data on KRAS and BRAF mutation status is limited in GC and has not been compared between GC from different geographic regions. METHODS: The prevalence of KRAS and BRAF mutations was established in 712 GC: 278 GC from the United Kingdom, 230 GC from Japan and 204 GC from Singapore. The relationship between KRAS/BRAF mutation status, DNA mismatch repair (MMR) status, clinicopathological variables and overall survival was analysed. RESULTS: Overall, 30 (4.2%) GC carried a KRAS mutation. In total, 5.8% of the UK GC, 4% of Japan GC and 1.5% of Singapore GC were KRAS mutant. KRAS mutant GC had fewer lymph node metastases in the UK cohort (P=0.005) and were more frequent in elderly patients in the Japan cohort (P=0.034). KRAS mutations were more frequent in MMR-deficient GC in the UK and the Japanese cohort (P<0.05). A BRAF mutation was only detected in a single Japanese GC. CONCLUSIONS: This large multicentre study demonstrated that KRAS mutations and DNA MMR deficiency have a role in a small subgroup of GC irrespective of country of origin, suggesting that this subgroup of GC may have developed along a common pathway. Further studies need to establish whether concomitant mutations or amplifications of other EGFR signalling pathway genes may contribute to the activation of this pathway in GC.
Subject(s)
DNA Mismatch Repair , DNA Repair-Deficiency Disorders , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins/genetics , Stomach Neoplasms/genetics , ras Proteins/genetics , Aged , Cohort Studies , ErbB Receptors/genetics , Female , Genes, ras , Humans , Immunohistochemistry , Male , Middle Aged , Proto-Oncogene Proteins p21(ras) , Stomach Neoplasms/enzymologyABSTRACT
BACKGROUND: To search for biomarkers identifying pancreatic cancer patients likely to benefit from adjuvant gemcitabine chemotherapy, we investigated the status of several histone modifications in pancreatic tumors and their relationship to clinicopathological features and outcomes. METHODS: Sixty one pancreatic cancer patients, primarily treated by surgical removal of tumors, were involved in the study. Thirty patients completed postoperative adjuvant gemcitabine, and in 31 it was discontinued. Tumor specimens were examined using immunohistochemistry for di- and tri-methylation of histone H3 lysine 4 (H3K4me2 and H3K4me3), dimethylation and acetylation of histone H3 lysine 9 (H3K9me2 and H3K9ac), and acetylation of histone H3 lysine 18 (H3K18ac). Positive tumor staining for each histone modification was used to classify patients into low- and high-staining groups, which were examined for relationships to clinicopathological features and clinical outcomes. RESULTS: High expression of H3K4me3 was related to the well and moderately differentiated tumor histological type (p = 0.012) and low expression of H3K4me2 was related to the presence of perineural invasion (p = 0.007). No cellular histone modifications were associated with overall or disease-free survival of patients as a whole. In the subgroup analyses, a low level of H3K4me2 was significantly associated with worse disease free survival in patients that completed adjuvant gemcitabine (p = 0.0239). Univariate and multivariate hazard models also indicated that a low level of H3K4me2 was a significant independent predictor of disease-free survival (p = 0.007). CONCLUSION: H3K4me2 was found to be a predictor of response to adjuvant gemcitabine in Asian patients with pancreatic cancer.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Deoxycytidine/analogs & derivatives , Histones/metabolism , Pancreatic Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Deoxycytidine/therapeutic use , Disease-Free Survival , Female , Humans , Immunohistochemistry , Lysine/metabolism , Male , Methylation , Middle Aged , Pancreatic Neoplasms/metabolism , GemcitabineABSTRACT
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but fatal tumour. Although most MPM patients show pleural effusion at even the early stage, it is hard to diagnose as MPM at the early stage because a sensitive and reliable diagnostic marker for MPM has not been found in plasma or pleural effusion. METHODS: In this study, we investigated whether intelectin-1 was specifically contained in MPM cells and the pleural effusion of MPM patient by immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay. RESULTS: Malignant pleural mesothelioma cell lines, but not lung adenocarcinoma cell lines, secreted intelectin-1. In immunohistochemistry, epithelioid-type MPMs, but neither pleura-invading lung adenocarcinomas nor reactive mesothelial cells near the lung adenocarcinomas, were stained with anti-intelectin antibodies. Pleural effusion of MPM patients contained a higher concentration of intelectin-1 than that of lung cancer patients. CONCLUSION: These results suggest that detection of intelectin-1 may be useful for a differential diagnosis of epithelioid-type MPM in immunohistochemistry and that a high concentration of intelectin-1 in pleural effusion can be used as a new marker for clinical diagnosis of MPM.
Subject(s)
Biomarkers, Tumor/metabolism , Cytokines/metabolism , Lectins/metabolism , Mesothelioma/metabolism , Pleural Effusion, Malignant/metabolism , Pleural Neoplasms/metabolism , Aged , Biomarkers, Tumor/analysis , Cell Line, Tumor , Cytokines/analysis , GPI-Linked Proteins , Humans , Lectins/analysis , Male , Middle Aged , Pleura/metabolism , Pleural Effusion, Malignant/chemistryABSTRACT
BACKGROUND: Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. METHODS: In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. RESULTS: Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. CONCLUSION: These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.
Subject(s)
Factor VII/metabolism , Ovarian Neoplasms/metabolism , Thromboplastin/metabolism , Venous Thromboembolism/etiology , Cell Hypoxia , Cell Line, Tumor , Cell-Derived Microparticles/metabolism , Female , Humans , Neoplasms, Glandular and Epithelial/chemistry , Ovarian Neoplasms/complications , Ovarian Neoplasms/pathologyABSTRACT
Carboplatin is one of the most commonly used and well-tolerated agents for gynecologic malignancies. The rate of hypersensitivity reactions (HSRs) in the overall population of patients receiving carboplatin has been reported to increase after multiple doses of the agent. We retrospectively analyzed the incidence, clinical features, management, or outcome of carboplatin-related HSRs in 113 Japanese patients with gynecologic malignancies and the possibility of rechallenge with the drug. We intravenously administered carboplatin after paclitaxel or docetaxel. Mild HSRs are resolved by temporary interruption of carboplatin infusion, an additional antihistamine, and/or a corticosteroid. If HSRs arose, carboplatin was diluted, not exceeding 1 mg/mL, and slowly infused over 2 hours in subsequent cycles. Ten patients experienced carboplatin HSRs, with an overall incidence of 8.85%. The first HSR episode was mild in all cases. When retreated with carboplatin, 4 exhibited severe HSRs. More than 9 cycles and/or more than 5000 mg of carboplatin administration significantly increased the incidence of HSRs. In particular, carboplatin treatment beyond 15 cycles and/or 8000 mg increased the risk of severe HSRs (P < 0.0001). The incidence of HSRs in the ovarian carcinoma group was significantly greater than that in the uterine carcinoma group (P = 0.0046). Careful attention should be paid to HSRs during carboplatin treatment beyond 9 cycles and/or 5000 mg. The rate of severe HSRs greatly increases beyond 15 cycles and/or 8000 mg. Further studies are needed to identify potential risk factors that may contribute to the development of carboplatin HSRs and to decrease the risk of reactions.
Subject(s)
Antineoplastic Agents/adverse effects , Carboplatin/adverse effects , Drug Hypersensitivity/etiology , Ovarian Neoplasms/drug therapy , Uterine Cervical Neoplasms/drug therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/secondary , Adenocarcinoma, Clear Cell/drug therapy , Adenocarcinoma, Clear Cell/secondary , Adult , Aged , Aged, 80 and over , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/secondary , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/secondary , Female , Humans , Incidence , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/pathology , Retrospective Studies , Treatment Outcome , Uterine Cervical Neoplasms/pathologyABSTRACT
The recommended therapy for genotype-2 chronic hepatitis C is a regimen of pegylated interferon alpha (peginterferon) plus ribavirin. This study was conducted to determine the value of early viral kinetics as a predictive factor for sustained virologic responder (SVR). Peginterferon alpha 2b (1.5 microg/kg/week) plus weight-based ribavirin (600-1000 mg/day) was administered to 51 patients with chronic HCV genotype 2 for 24 weeks. The HCV-RNA loads were measured at the baseline, hour 24, and week 1. The rebound index (RI, an index obtained from the viral load of week 1 divided by that of hour 24) was calculated. Compared with the baseline, the viral load at hour 24 for SVR was reduced by more than 1-log: it continued to decline thereafter, and at week 1 it was significantly lower than at hour 24 (P < 0.05). The viral load for non-SVR increased again between hour 24 and week 1. The SVR of patients with RI Subject(s)
Antiviral Agents/therapeutic use
, Hepacivirus/classification
, Hepatitis C, Chronic/drug therapy
, Interferon-alpha/therapeutic use
, Ribavirin/therapeutic use
, Viral Load
, Adult
, Aged
, Antiviral Agents/administration & dosage
, Asian People
, Female
, Genotype
, Hepacivirus/genetics
, Hepacivirus/isolation & purification
, Hepatitis C, Chronic/virology
, Humans
, Interferon alpha-2
, Interferon-alpha/administration & dosage
, Male
, Middle Aged
, Polyethylene Glycols
, RNA, Viral/blood
, Recombinant Proteins
, Ribavirin/administration & dosage
, Treatment Outcome
ABSTRACT
Uterine cervical and endometrial cancers are common malignant solid neoplasms for which there are no useful prognostic markers. In this study, we evaluate the relationship between ATP-binding cassette superfamily F2 (ABCF2) expression and clinical factors including clinical stage, histologic type, grade and prognosis in uterine cervical and endometrial cancer. Two hundred and sixty seven cervical and 103 endometrial cancers were studied. ATP-binding cassette superfamily F2 cytoplasmic expression was detected by immunohistochemical staining and scored as positive or negative. Among cervical cancer cases, 149 (55.8%) expressed ABCF2. The overall survival was longer in ABCF2-negative than ABCF2-positive cases (P=0.0069). Statistically significant prognostic factors for survival were ABCF2 positivity (risk ratio (rr)=1.437), old age (rr=1.550) and advanced stage (rr=2.577). ATP-binding cassette superfamily F2 positivity was an independent prognostic factor by multivariate proportional hazard test (P=0.0002). Among endometrial cancer cases, 72 (69.9%) were cytoplasmic ABCF2 positive. However, there was no significant relationship between ABCF2 expression and age, clinical stage, histologic type, histologic grade, oestrogen receptor status or prognosis. ATP-binding cassette superfamily F2 expression may be a useful prognostic marker in cervical but not endometrial cancer. The role of ABCF2 protein may differ depending on the type of cancer.
Subject(s)
ATP-Binding Cassette Transporters/biosynthesis , Uterine Neoplasms/genetics , Uterine Neoplasms/metabolism , ATP-Binding Cassette Transporters/genetics , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Predictive Value of Tests , Prognosis , Uterine Neoplasms/pathology , Uterine Neoplasms/therapy , Young AdultSubject(s)
Facial Pain/therapy , Pain, Intractable/therapy , Subthalamic Nucleus/pathology , Carboxy-Lyases/antagonists & inhibitors , Deep Brain Stimulation , Facial Pain/etiology , Female , Humans , Levodopa/pharmacology , Middle Aged , Pain, Intractable/etiology , Parkinson Disease/complications , Parkinson Disease/therapy , Postoperative Period , Subthalamic Nucleus/physiology , Time Factors , Treatment OutcomeABSTRACT
PURPOSE: Sentinel lymph node biopsy (SNB) has been a standard technique in early breast cancer. However, it is not clear that the SNB procedure can be applied to second breast cancer or recurrence occurring in the previously treated breast. The purpose of this study was to clarify the feasibility of the SNB procedure in breast cancer occurring in the previously treated breast, and to investigate the factors related to altered lymphatic flow. PATIENTS AND METHODS: Between April 2004 and December 2006, 1490 patients underwent the breast SNB procedure. Among them, 31 patients had a history of previous treatments in the same breast. Recent excision biopsy cases were not included in this group. All patients had previous breast-conserving surgery in the same breast. Sixteen patients had axillary dissection, 3 had SNB, and 12 had no axillary treatment. Ten patients had received radiation therapy to the breast and axilla. Visualization of axillary nodes, internal mammary nodes and contralateral axillary nodes was evaluated and compared with pathological results. RESULTS: Axillary nodes were visualized in 23 patients, internal mammary nodes in 7 patients, and contralateral axillary nodes in 7 patients. The patients with previous axillary dissection exhibited altered lymph node distribution, but did not show involvement of contralateral axillary nodes. Visualization of contralateral axillary nodes occurred in 7 of the 10 patients with previous irradiation to breast irrespective of axillary dissection. Twenty-eight patients underwent SNB, 4 of whom showed cancer-positive nodes. Three patients were cancer-positive in non-ipsilateral axillary nodes (one patient showed positive opposite axillary node and two patients showed positive internal mammary nodes). CONCLUSION: Previous axillary dissection or irradiation to the breast greatly influences lymphatic flow. Irradiation to the breast may be a strong factor for the visualization of contralateral axillary nodes. Despite the frequent alteration of lymphatic flow, SNB seems to be feasible in secondary or recurrent breast cancer patients.
Subject(s)
Breast Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Neoplasms, Second Primary/pathology , Sentinel Lymph Node Biopsy , Axilla , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Feasibility Studies , Female , Humans , Lymph Node Excision , Lymphatic System/radiation effects , Lymphatic System/surgery , Mastectomy, SegmentalABSTRACT
To evaluate the usefulness of computerized brain-surface dynamic voltage topography (DVT) of ictal electrocorticographic (ECoG) discharges to localize and identify epileptogenic areas, 3 patients with intractable frontal lobe epilepsy who underwent epilepsy surgery after chronic subdural electrode recording were assessed. Cortical surfaces and subdural electrodes were photographed during initial surgery to create an electrode map that could be superimposed onto a picture of the brain surface. DVT was performed by calculating sequential amplitudes of ictal ECoG discharges, which were then superimposed onto the cortical and electrode maps. In all cases, DVT clearly identified the ictal onset zone and the early propagation area on the operative field. DVT allowed recognition of spatial relationships between the epileptogenic area and structural abnormalities, functional cortex, and cortical veins; and was useful to decide on the resection area.
Subject(s)
Brain Mapping/methods , Cerebral Cortex/physiopathology , Epilepsy, Frontal Lobe/physiopathology , Adolescent , Adult , Cerebral Cortex/pathology , Electrodes , Electroencephalography/methods , Epilepsy, Frontal Lobe/pathology , Female , Humans , Image Processing, Computer-Assisted , MaleABSTRACT
There have been controversies whether maternal serum placental protein 5 (PP5)/tissue factor pathway inhibitor (TFPI)-2 is increased in the patients with preeclampsia and/or intrauterine growth restriction (IUGR). Here, we have estimated the serum PP5/TFPI-2 in these patients by a sandwich enzyme-linked immunosorbent assay with a newly developed monoclonal antibody, coupled with placental immunohistochemical studies of their placentae with semiquantitative scoring. Serum PP5/TFPI-2 level was significantly elevated only in the patients with preeclampsia alone (p=0.033), while PP5/TFPI-2 was detected significantly less intensely in the placentae of the same patients (p=0.035) in immunohistochemistry, as compared to Controls. A proteoglycan present on the placental villous surface, glypican-3, showed the same pattern of staining as PP5/TFPI-2, and there was a positive correlation (C.I.=0.506, p=0.004) between the immunohistochemical scores for these. Further experiments using HepG2 cells transfected with PP5/TFPI-2 suggested that glypican-3 could anchor PP5/TFPI-2 on the placental villi. A possibility that a decrease in glypican-3 in the placenta increases the outflow of PP5/TFPI-2, which in turn increases its serum level, was proposed. Preeclampsia and IUGR, often regarded to have the same pathological basis in common, showed distinct distributions of PP5/TFPI-2, which could be a clue to elucidate the pathogenesis of preeclampsia and IUGR.
Subject(s)
Fetal Growth Retardation/metabolism , Glycoproteins/metabolism , Glypicans/metabolism , Placenta/metabolism , Pre-Eclampsia/metabolism , Adult , Female , Fetal Growth Retardation/blood , Glycoproteins/blood , Humans , Immunohistochemistry , Infant, Newborn , Male , Pre-Eclampsia/blood , Pregnancy , Syndecan-1/metabolismABSTRACT
We conducted a feasibility study to examine whether small numbers of cancer cells could be utilised for analysis of the EGFR gene status using the loop-hybrid mobility shift assay, which is a modified heteroduplex technique. Cytology specimens obtained by transbronchial abrasion were successfully used for analysis of the EGFR gene status in 50 of 52 (96.2%) patients diagnosed with class V non-small-cell carcinoma. Furthermore, the relationship between the EGFR gene status and clinical outcome was analysed in 25 patients treated with gefitinib. Overall, 10 of 11 patients with EGFR mutations in exon 19 or 21 showed tumour regression with gefitinib treatment, compared to only two of 14 patients with wild-type EGFR. The response rate was significantly higher in the EGFR mutation group than in the wild-type EGFR group (90.9 vs 14.3%, P=0.00014). Logistic regression analysis revealed that EGFR mutations in cytology specimens represented an independent predictor of the gefitinib response. The overall and progression-free survivals were significantly longer in the EGFR mutation group than in the wild-type EGFR group (P<0.05). In conclusion, cytology specimens could be useful for analysing the EGFR status in the majority of patients with non-small-cell lung cancer to determine whether they are likely to benefit from gefitinib treatment.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Mutation/genetics , Quinazolines/therapeutic use , Adult , Aged , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Chi-Square Distribution , DNA Mutational Analysis/methods , ErbB Receptors/antagonists & inhibitors , Female , Gefitinib , Humans , Kaplan-Meier Estimate , Logistic Models , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Nucleic Acid Heteroduplexes/genetics , Treatment OutcomeABSTRACT
Pelizaeus-Merzbacher disease (PMD) is a rare X-linked leukodystrophy caused by proteolipid protein 1 (PLP1) gene mutations. Previous studies indicated that proteolipid proteins (PLPs) with disease-associated mutations are misfolded and trapped in the endoplasmic reticulum (ER) during transportation to the cell surface, which eventually leads to oligodendrocyte cell death in PMD. Here we report a PMD patient with a very mild phenotype carrying a novel mutation (485G-->T) in exon 4 of the PLP1 gene that causes a Trp(162)Leu substitution in the protein. We also investigated intracellular trafficking of this mutant PLP in COS-7 cells. Transiently transfected mutant PLP(W162L) fused to an enhanced green fluorescent protein (EGFP) or a short peptide tag was not carried to the plasma membrane. However, in contrast to previous studies, this mutant PLP was not retained in the ER, indicating an escape of the newly translated protein from the quality control machinery. We also found that the mutant PLP accumulated in the nuclear envelope (NE) in a time-dependent manner. This mutant PLP, with its distribution outside the ER and a very mild phenotype, supports the idea that accumulation of misfolded mutant protein in the ER causes the severe phenotype of PMD.
Subject(s)
Membrane Proteins/metabolism , Myelin Proteolipid Protein/metabolism , Pelizaeus-Merzbacher Disease/metabolism , Animals , COS Cells , Child, Preschool , Chlorocebus aethiops , Cloning, Molecular/methods , Exons , Fluorescent Antibody Technique/methods , Gene Expression/genetics , Green Fluorescent Proteins/metabolism , Humans , Leucine/genetics , Magnetic Resonance Imaging/methods , Male , Membrane Proteins/genetics , Mutagenesis/physiology , Mutation/genetics , Myelin Proteolipid Protein/genetics , Pelizaeus-Merzbacher Disease/genetics , Pelizaeus-Merzbacher Disease/pathology , Protein Transport/physiology , Receptors, Peptide/metabolism , Subcellular Fractions/metabolism , Time Factors , Transfection/methods , Tryptophan/geneticsABSTRACT
AIMS: The aim of the present study is to clarify the level of radioactive lymph node should be biopsied after the most radioactive SN is removed. METHODS: SNB using radionuclide was performed in our hospital for 1179 primary breast cancers between April 2000 and October 2005; most (1177/1179) were performed successfully. Our criterion for harvesting SNs is to remove tissue until no radioactive site is present. The level of radioactivity and the order of removal of each lymph node were compared with pathologic results. RESULTS: More than 2 (overall average 1.9) radioactive SNs were biopsied in 686 of 1177 breasts. Cancer positive results were recorded for 142 breasts with multiple SNs. In 142 breasts, 64 showed metastasis to the most radioactive node only, 39 showed metastasis other than the most radioactive node only, and 39 showed the most radioactive node and other radioactive nodes. Moreover, if several other criteria were applied, false-positive cases were increased significantly. CONCLUSIONS: It is necessary to harvest radioactive lymph nodes other than the most radioactive. Moreover, efforts to remove every radioactive lymph node will minimize false-negative results.
Subject(s)
Breast Neoplasms/pathology , Lymph Nodes/radiation effects , Organotechnetium Compounds , Phytic Acid , Radiopharmaceuticals , Rhenium , Sentinel Lymph Node Biopsy , Technetium Compounds , Axilla , False Negative Reactions , False Positive Reactions , Female , Humans , Radiation DosageABSTRACT
AIMS: To study the significance of lymphatic drainage disruption due to a surgical scar in sentinel node mapping (SNM) in breast cancer patients. METHODS: We reviewed patients with stage I breast cancer who had undergone SNM and had an old surgical scar in the ipsilateral breast. RESULTS: Of 534 breast cancer patients who had undergone SNM, five patients had an old scar in the ipsilateral breast. Inter-pectoral nodes, internal nodes, intramammary nodes, and contralateral axillary nodes were identified as sentinel nodes in three cases. In the remaining two cases, no sentinel lymph nodes were identified. CONCLUSIONS: An old surgical scar in the breast may cause lymphatic drainage disruption, resulting in abnormal radioactive colloid uptake during SNM.
Subject(s)
Breast Neoplasms/pathology , Cicatrix/pathology , Sentinel Lymph Node Biopsy/methods , Aged , Axilla , Breast , Carcinoma in Situ/pathology , Carcinoma in Situ/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/surgery , Coloring Agents , Female , Humans , Lymph Node Excision , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Mastectomy , Mastectomy, Segmental , Middle Aged , Neoplasm Recurrence, Local/pathology , Pectoralis Muscles , Radionuclide Imaging , RadiopharmaceuticalsABSTRACT
A 15-year-old girl developed intractable epilepsy following a right transcallosal resection of the intraventricular teratoma. Magnetic resonance (MR) imaging showed a T (2)-prolonged subcortical lesion in the right frontal lobe as well as a residual intraventricular tumor. The integration of the voltage topography of ictal onset activities of the scalp-recorded electroencephalogram (EEG) and a surface anatomy scan of MR images clearly revealed the epileptogenic area on the cortex above the subcortical lesion, with the propagation pattern towards the frontopolar area. Excision of the epileptogenic cortex and underlying gliosis resulted in a successful cessation of the epilepsy. This non-invasive EEG technique provided useful information that accurately localized the epileptogenic area on a large structural abnormality without invasive intracranial electrocorticographic monitoring.