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Detection of EGFR mutation in lung adenocarcinoma and paired plasma田珮芝, Tin, Pui-chi. January 2008 (has links)
published_or_final_version / Medical Sciences / Master / Master of Medical Sciences
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Mutations of epidermal growth factor receptor (EGFR) pathway genes andMET in primary lung adenocarcinomaHo, Ka-yan, Rebecca Lucinda., 何嘉茵. January 2012 (has links)
This study completed the analysis of mutational frequencies and clinicopathological patterns of six EGFR pathway-related genes (EGFR, HER2, HER4, KRAS, BRAF and MET) in 212 resected lung adenocarcinomas (AD) from 98 male and 114 female Chinese patients without prior chemotherapy or tyrosine kinase inhibitor (TKI) therapy. Genomic DNA and cDNA sequencing, quantitative PCR and fluorescence in-situ hybridization (FISH) were employed to investigate mutation and amplification status of the relevant genes. Overall, more than 75% of tumours were detected to harbour mutations or amplification in one of these six genes. The commonest mutation was found to involve EGFR, comprising 60.38% of cases, followed by KRAS (9.43%), HER2 (2.36%), MET (2.36%), BRAF (1.42%) and HER4 (0.47%). Four somatic mutations in MET exon 14 splicing region were found, leading to alternative splicing and a transcript lacking exon 14. Two of the MET mutant tumours and one MET wild-type tumour showed MET amplification of more than 3.5 fold increase in copy number. Mutations of EGFR were significantly more frequent in female (p = 0.0196), non-smokers (p < 0.001) and well differentiated tumours (p = 0.0209). KRAS mutations showed significant association with male (p = 0.0099) and smoking history (p = 0.0011). A novel HER2 D769Y mutation was found and HER2 mutations were associated with smokers (p = 0.0013) and poorly differentiated tumours (p = 0.0147). BRAF, MET mutations and MET amplification were not associated with clinicopathological factors. Mutations were mutually exclusive except for two cases with KRAS and HER4/BRAF. MET amplification was co-existent with MET mutations in two cases. MET amplification was found to negatively correlate with disease-free and cancer-specific survivals. The results suggested that MET amplification may contribute to disease progression and could be a therapeutic target in primary lung AD in Hong Kong Chinese patients. / published_or_final_version / Pathology / Master / Master of Medical Sciences
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The effect of reconstruction algorithms (iterative versus filtered backprojection) on the diagnosis of single pulmonary nodules using Thallium-201 and Technetium-99m MIBI SPECTAmbayi, Rudo 04 1900 (has links)
Thesis (MScMed)--Stellenbosch University, 2004. / Copy not signed by author. / ENGLISH ABSTRACT: This study involved 33 patients, 19 men and 14 women. The age range was wide (20-90
years) and median age was 57 years. These patients had a single pulmonary nodule (SPN)
defined radiologically as a well defined, round or oval intrapulmonary lung lesion not
associated with atelectasis or adenopathy on chest radiography or computed tomography.
Patients were investigated with Tc-99m MIBI and TI-201 (25 patients) and with Tc-99m
MIBI alone (8 patients). Single photon emission computed tomography images were
reconstructed using both iterative reconstruction (Ordered Subsets - Expectation
Maximisation: aSEM) and filtered backprojection (FBP), on the Hermes system.
Transverse, coronal and sagittal slices were displayed on the screen using a grey scale.
The aSEM and FBP images for each study were co-registered semi-automatically using
the multimodality programme on the Hermes. The best slice for the lesion was chosen
according to the best view used to locate the SPN on chest radiograph. Regions of interest
(Ral) were drawn manually outside the outer margin of the detected lesion, first on the
aSEM image. This was automatically mirrored on the co-registered FBP image.
For most patients, the background was automatically mirrored horizontally on the
contralateral side, again, first on the OSEM then automatically on the FBP image.
Automatic vertical mirroring or manual horizontal mirroring was used when background
was found to be in a visually 'hot' area like the heart or vertebrae. The average counts
and standard deviation of the Ral and background were generated automatically.
Semi-quantitative image analysis was done by calculating the signal-to-noise ratio (SNR)
and tumour-to-background (TIB) ratio using the following formulae:
SNR = Mean counts ROI(lesion) - Mean counts background
Standard deviation background
TIB rati.o = -M---e-a-n-'--c-o--u-n-'t-s- ROI(lesion)
Mean counts background
Detection was found to be the same for the two reconstruction algorithms, that is, every
lesion detected by using OSEM could also be detected by using FBP.
However lesion detection did differ between Tl-201 and Tc-99m-MIBI.
Sensitivity and specificity were calculated for different thresholds of SNR and TIB ratios.
Receiver operating characteristics (ROC) curves were drawn to represent the different
sensitivities and specificities at each threshold. Tuberculosis (TB) was not included in
this analysis as uptake of Tl-20l was found to be significantly high and comparable to
that of malignant nodules. However the effect of OSEM and FBP on the 'positive' TB
nodules was assessed separately. By calculating the area under the ROC curves, TI-201
using OSEM was shown to be more accurate at differentiating malignant nodules from
benign ones than FBP. Although this difference was not statistically significant (p=0.1 0),
there was a clear tendency. The two reconstruction algorithms were found to be almost
equally accurate, when using Tc-99m-MIBI, the difference between them being
considerably insignificant.
In conclusion, it was shown that there is a tendency that OSEM outperforms FBP for
studies using Tl-201 but not for Tc-99m-MIBI. / AFRIKAANSE OPSOMMING: Hierdie studie sluit 33 pasiënte in, 19 mans en 14 vroue. Die ouderdomme wissel tussen
20 en 90 jaar met 'n gemiddelde ouderdom van 57 jaar. Elkeen van die pasiënte het 'n
enkel longnodule (SPN) op borskas X-straal en/of rekenaar tomografie getoon, wat
radiologies gedefinieer word as 'n goed omskrewe, ronde of ovaal intrapulmonale
longletsel wat nie met atelektase of adenopatie geassosieer is nie.
Pasiënte is met Tc-99m MIDI en TI-201 (25 pasiënte) of slegs met Tc-99m MIBI (8
pasiënte) ondersoek. Enkelfoton emissie rekenaar tomografiese (EFERT) beelde is met
beide iteratiewe rekonstruksie (Ordered Subsets - Expectation Maximisation: OSEM) en
gefilterde terugprojeksie (FBP) met die Hermes sisteem gerekonstrueer.
Transvers, koronale en sagittale snitte is in grysskaal op die sisteem vertoon. Die OSEM
en FBP beelde vir elke studie is semi-outomaties gekoregistreer met behulp van die
multimodaliteitsprogram op die Hermes. Die optimale snit vir elke letsel is gekies
volgens die beste aansig op die borskas X-straalom die SPN te lokaliseer. Gebiede van
belang (ROl) is met die hand buite-om die buitenste rand van die letsel getrek op die
OSEM beeld en daarna outomaties in die ooreenstemmende area op die gekoregistreerde
FPB beeld geplaas.
Vir die meeste pasiënte is die agtergrond outomaties as horisontale spieëlbeeld op die
kontralaterale kant geplaas, eers op die OSEM en dan outomaties op die FBP beeld. 'n
Outomatiese vertikale spieëlbeeld of manuele horisontale verskuiwing van die
agtergrondsarea is gedoen indien die agtergrond oorvleuel het met 'n 'warm' area soos
die hart of werwels. Die gemiddelde tellings en standaardafwyking van die ROl en
agtergrond is outomaties gegenereer.
Semi-kwantitatiewe beeldanalise is gedoen deur berekening van die sein-tot-agtergrond
verhouding (signal-to-noise ratio - SNR) en tumor-tot-agtergrond (TIB) verhouding met
behulp van die volgende formules:
SNR = gemiddelde tellings ROI(letsel) - gemiddelde tellings agtergrond
Standaard afwyking van agtergrond
TIB rati.o = -g=em--id-d-e-l-d-e--te=ll-in-g-s__R:_O-I(-le-t-s'e-l)
gemiddelde tellings agtergrond
Opsporing is soortgelyk bevind vir die twee rekonstruksie algoritmes, dit wil sê elke
letselopgespoor met behulp van OSEM kon ook met FBP opgespoor word.
Letselwaameming het egter verskil tussen TI-201 en Tc-99m-MIBI.
Sensitiwiteit en spesifisiteit is vir verskillende drempels van SNR en TIB verhoudings
bereken. 'Receiver operating characteristics' (ROC) kurwes is getrek om die verskillende
sensitiwiteite en spesifisiteite by elke drempel te verteenwoordig. Tuberkulose (TB) is nie
in hierdie analise ingesluit nie aangesien opname van Tl-201 beduidend hoog en
vergelykbaar met die van maligne nodules was. Die effek van OSEM en FBP op die
'positiewe' TB nodules is egter apart beoordeel. Deur berekening van die area onder die
ROC kurwes, is getoon dat OSEM van Tl-201 tomografiese data meer akkuraat as FBP
was om maligne van benigne nodules te onderskei. Alhoewel hierdie verskil nie statisties
betekenisvol was nie (p=0.10), is daar wel 'n duidelike neiging gevind. Die twee
rekonstruksie algoritmes was byna ewe akkuraat wanneer Tc-99m-MIBI gebruik is, met
duidelik geen betekenisvolle verskil tussen die algoritmes nie.
Gevo lgtrekking
In hierdie studie is dit getoon dat daar 'n neiging is dat OSEM beter vaar as FBP vir
studies met tallium-201 maar nie vir Tc-99m-MIBI nie.
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