Abstract:
OBJECTIVE:Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy, most frequently affecting the head and neck. Treatment often requires surgery and can have significant functional morbidity. Research into disease pathogenesis and second line medical management of cSCC is limited. We assess genetic mutations in high-risk, primary head and neck cutaneous squamous cell carcinomas (HNcSCC) that may hinder or be beneficial for use of targeted therapy in disease management. METHODS:Genetic alterations and variant allele frequencies (VAFs) were analysed using a clinically relevant 48 gene panel in 10 primary high-risk non-metastatic treatment-naïve HNcSCC to evaluate applicability of targeted therapeutics. Variants present at all VAFs were evaluated for pathogenicity. Somatic mutation patterns of individual tumours were analysed. RESULTS:High-risk HNcSCC showed a high proportion (82%) of C to T transitions in keeping with ultraviolet-mediated damage. There was significant intratumour genetic heterogeneity in this cohort (MATH scores 20-89) with the two patients <45 years of age showing highest intratumour heterogeneity. TP53 was altered at VAF >22% in all cases, and mutations with highest VAF were observed in tumour suppressor genes in 80%. 70% of cases demonstrated at least one mutation associated with treatment resistance (KIT S821F, KIT T670I, RAS mutations at codons 12 and 13). CONCLUSION:We demonstrate high proportion tumour suppressor loss of function mutations, high intratumour genetic heterogeneity, and presence of well recognised resistance mutations in treatment naïve primary HNcSCC. These factors pose challenges for successful utilisation of targeted therapies.
journal_name
J Clin Patholjournal_title
Journal of clinical pathologyauthors
Zilberg C,Lee MW,Kraitsek S,Ashford B,Ranson M,Shannon K,Iyer NG,Ch'ng S,Low TH,Palme C,Clark J,Gupta R,Yu Bdoi
10.1136/jclinpath-2019-206038subject
Has Abstractpub_date
2020-01-01 00:00:00pages
17-22issue
1eissn
0021-9746issn
1472-4146pii
jclinpath-2019-206038journal_volume
73pub_type
杂志文章abstract::This report describes a left adrenal tumour in a 16 year old Chinese girl who presented with fever of unknown origin. The histological and ultrastructural features of the adrenal tumour were those of a primitive small round cell tumour with neuroendocrine differentiation. Cytogenetic analysis of cultured tumour cells ...
journal_title:Journal of clinical pathology
pub_type: 杂志文章,评审
doi:10.1136/jcp.54.12.966
更新日期:2001-12-01 00:00:00
abstract::The production of heparinase by a wide range of anaerobic bacteria isolated from clinical specimens was investigated. None of the 29 strains of Bacteroides fragilis produced heparinase. Of 62 other Bacteroides tested, only two of four strains of B ovatus, two of three strains of B thetaiotaomicron, and two of four str...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.40.4.384
更新日期:1987-04-01 00:00:00
abstract:AIMS:Marked thrombocytosis is uncommon in chronic myelogenous leukaemia (CML) but may be associated with mutation of JAK2 V617F, calreticulin (CALR) and/or phospho-STAT5 (p-STAT5) activation in other myeloproliferative neoplasms (MPNs), particularly essential thrombocythaemia (ET). We investigated the JAK2 V617F, CALR ...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jclinpath-2015-203498
更新日期:2016-08-01 00:00:00
abstract::A method of typing Pseudomonas pyocyanea is described which makes use of the property of bacteriocine production. The method was applied in an epidemiological study of Ps. pyocyanea infection in a general hospital. It was found that the majority of strains believed on epidemiological grounds to be of common origin wer...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.17.3.236
更新日期:1964-05-01 00:00:00
abstract::A technique, using indirect immunoperoxidase antibody (IPA), was developed for the detection of IgG antibody to Chlamydia trachomatis. The IPA technique employs glass slides with air-dried and acetone-fixed C trachomatis infected cells, which can be stored at -70 degrees C and used for several months. Antibody titres ...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.36.3.353
更新日期:1983-03-01 00:00:00
abstract::The distribution of laminin, a basement membrane glycoprotein, was studied by an immunohistochemical technique in six samples of benign sclerosing lesions of extrahepatic bile ducts and in 11 sclerosing cholangiocarcinomas. The expression of laminin showed that benign glandular structures were surrounded by a mainly i...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.42.9.927
更新日期:1989-09-01 00:00:00
abstract:AIMS:To institute recommendations from a laboratory turnround time study; to evaluate audit methods; and to quantify improvements achieved. METHODS:Changes to result report distribution and specimen delivery were affected by posting results directly from the laboratory followed by the introduction of a twice daily cou...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.48.4.372
更新日期:1995-04-01 00:00:00
abstract::Infection with Vibrio vulnificus is uncommon in Europe but is associated with necrotising wound infections and life-threatening septicaemia. This case is one of infection most likely to have been acquired from a thermal pool in Turkey without preceding exposure to seawater or shellfish. The report also describes how e...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.2008.059238
更新日期:2009-04-01 00:00:00
abstract:AIMS:To assess changes in volume and complexity of cellular pathology workload after clinical service reorganisation and alterations in pathology reporting practices, and to identify objective measures of change applicable to all cellular pathology departments. The ear, nose, and throat (ENT), head and neck (HN) specia...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.57.1.22
更新日期:2004-01-01 00:00:00
abstract::In cases of adult T cell leukaemia neoplastic T cell infiltration in the skin was accompanied by an increase in Langerhans cells. This is in keeping with the view that Langerhans cells may induce antigen-specific and allogenic T cell activation. ...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.36.3.307
更新日期:1983-03-01 00:00:00
abstract::Painful lymphadenopathy developed in eight female patients after massive infusions of iron dextran for sideropaenic anaemia. Fever, arthralgias, and malaise were also features of the clinical picture. The histology of one lymph node is described and changes in it are discussed in relation to the pathogenesis of the sy...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.21.4.492
更新日期:1968-07-01 00:00:00
abstract::Inhibition of streptolysin O activity by cholesterol depends on the latter being in free form. The normal esterified and protein-bound cholesterol fractions in serum do not influence streptolysin O activity. However, high cholesterol levels in rabbits fed cholesterol with cholic acid were associated with an increased ...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.25.10.885
更新日期:1972-10-01 00:00:00
abstract::Strokes are one of the most common causes of mortality and long term severe disability. There is evidence that lipoprotein (a) (Lp(a)) is a predictor of many forms of vascular disease, including premature coronary artery disease. Several studies have also evaluated the association between Lp(a) and ischaemic (thrombot...
journal_title:Journal of clinical pathology
pub_type: 杂志文章,评审
doi:10.1136/jcp.53.7.487
更新日期:2000-07-01 00:00:00
abstract::Serum total calcium was measured in 1693 patients during a four-month period. We examined the effects of adjustment for albumin concentration on the interpretation of single measurements of serum total calcium and on the variation of series of measurements in individual patients. Markedly abnormal total calcium concen...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.32.1.56
更新日期:1979-01-01 00:00:00
abstract:BACKGROUND:Serum prostate specific antigen (PSA) increases after radical prostatectomy are thought to indicate recurrent disease, although some suggest they result from benign prostatic epithelial tissue left at surgical margins. AIMS:To investigate whether presence, location, and extent of benign prostatic tissue at ...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.2004.024182
更新日期:2005-07-01 00:00:00
abstract::Although the UK National Institute for Health and Care Excellence guidelines recommend that in patients with biopsy-proven invasive lobular carcinoma (ILC), preoperative MRI scan is considered, the accuracy of diagnosis of ILC in core biopsy of the breast has not been previously investigated. Eleven pathology laborato...
journal_title:Journal of clinical pathology
pub_type: 杂志文章,多中心研究
doi:10.1136/jclinpath-2016-203886
更新日期:2016-12-01 00:00:00
abstract::The cytological features of testicular germ cell tumours were established in smears from 15 freshly resected tumours. These features were applied to the fine needle aspiration cytology diagnosis of metastases in 27 patients referred for chemotherapy. There were 16 positive reports in 32 aspirates of which 13 were take...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.40.11.1324
更新日期:1987-11-01 00:00:00
abstract::A manual system of microbiology reporting with a National Cash Register (NCR) form with printed names of bacteria and antiboitics required less time to compose reports than a previous manual system that involved rubber stamps and handwriting on plain report sheets. The NCR report cost 10-28 pence and, compared with a ...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.29.6.553
更新日期:1976-06-01 00:00:00
abstract:BACKGROUND:The disorders associated with metabolic syndrome (MS) can lead to renal disease. IgA nephropathy is the most common form of glomerulonephritis, and many patients with this disorder progress to renal failure. AIMS:To identify the effect of MS on IgA nephropathy by retrospectively comparing patients who had I...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.2009.074278
更新日期:2010-08-01 00:00:00
abstract::Gastrointestinal cell proliferation plays an important role in the maintenance of the integrity of the gastrointestinal system. The study of gastrointestinal proliferation kinetics allows a better understanding of the complexity of the system, and also has important implications for the study of gastrointestinal carci...
journal_title:Journal of clinical pathology
pub_type: 杂志文章,评审
doi:10.1136/jcp.52.5.321
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND:A genetic component to the development of chronic fatigue syndrome (CFS) has been proposed, and a possible association between human leucocyte antigen (HLA) class II antigens and chronic fatigue immune dysfunction has been shown in some, but not all, studies. AIMS:To investigate the role of HLA class II ant...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.2004.022681
更新日期:2005-08-01 00:00:00
abstract::One hundred prostates from 20 to 40 year old men obtained at necropsy were completely sectioned and studied microscopically. Atypical hyperplasia was found in 10 (20%) of 20-29 year old men and in 12 (24%) of 30-40 year old men. The prostates with atypical hyperplasia had similar weights as those without, and the atyp...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.42.4.383
更新日期:1989-04-01 00:00:00
abstract:AIMS:To investigate the histopathological features of the synovial lining of the knee following implantation of an artificial cruciate ligament. METHODS:Eighty two patients underwent anterior cruciate ligament reconstruction for chronic, symptomatic instability of the knee. The cruciate ligament was reconstructed with...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.48.6.556
更新日期:1995-06-01 00:00:00
abstract::Three hundred and sixty samples of blood from 230 hospital patients were examined and compared with the results of simultaneous blood culture to determine the value of buffy-coat microscopy in detecting bacteraemia. One observer found 86 positive smears, 12 of which were from patients with positive blood cultures and ...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.34.12.1375
更新日期:1981-12-01 00:00:00
abstract::A method of typing isolates of Proteus mirabilis and Proteus vulgaris is described based on the sensitivity of the organisms to bacteriocine. Twelve standard proteocine producing strains were selected from a large number of isolates tested, and from these liquid proteocine preparations were prepared. The sensitivities...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.28.10.784
更新日期:1975-10-01 00:00:00
abstract::The effect of the new beta-lactam antibiotic FL 1060 on urinary tract pathogens, of which 71 were sensitive to and 100 resistant to ampicillin, is presented here. When tested by conventional methods FL 1060 was found to be highly active against ampicillin-sensitive strains of E. coli but phenotypically resistant varia...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.27.3.192
更新日期:1974-03-01 00:00:00
abstract::Performance of CHROMagar Acinetobacter was assessed for the selective isolation and identification of Acinetobacter baumannii. The medium was effective in suppressing the growth of other Gram-positive and Gram-negative species while the addition of KPC supplement ensured growth of only carbapenem resistant A baumannii...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.2010.083469
更新日期:2011-02-01 00:00:00
abstract:AIMS:Although the autopsy is still the gold standard for quality assessment of clinical diagnoses, autopsy rates have been declining over the last decades to <10%. The aim of this study was to investigate the value of autopsies in the high-tech medicine era by determining the frequency of discrepancies between clinical...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jclinpath-2013-202122
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVE:We explore factors such as the blood sampling site (capillary vs venous), the equipment (HemoCue vs automated haematology analyser) and the model of the HemoCue device (201+ vs 301) that may impact haemoglobin measurements in capillary and venous blood. METHODS:Eleven studies were identified, and bias, conco...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jclinpath-2020-206717
更新日期:2020-10-06 00:00:00
abstract::Four assays for the detection of alphafetoprotein (AFP) in the diagnosis of primary hepatocellular carcinoma (HCC) were evaluated. The frequency of AFP detection was compared in 89 HCC patients and in 71 patients with chronic active hepatitis/cirrhosis. Of the four assays, immunodiffusion, counterimmunoelectrophoresis...
journal_title:Journal of clinical pathology
pub_type: 杂志文章
doi:10.1136/jcp.33.8.792
更新日期:1980-08-01 00:00:00