MATERIALS AND METHODS: All cases received by the Department of Pathology for histopathological examination between 1 July 2018 and 30 June 2019 were retrieved from the Laboratory Information System (LIS). All the IHC requests over this period were tabulated, with the exception of renal, muscle, rectal and nerve biopsies with their pre-defined algorithms for stains and cytological specimens. IHC stains performed solely for purpose of directing targeted treatment were also not included.
RESULTS: Immunohistochemistry was performed in 2044 (21.1%) of the total of 9686 cases, with a total of 5969 IHC stains performed i.e. 2.9 (5969/2044) IHC stains per case. All 91 antibodies available were used at least once during the study. 14 histopathologists (5 with < 10-years and 9 with ≥ 10-years postgraduate specialist experience) reported on the cases with no significant difference (p=0.90) in their usage of IHC stains. Among the most common IHC stains used, requests for Ki67 and MNF116 showed higher standard deviations compared with p63, CK7 and S100 among the histopathologists. From the relatively higher standard deviation for Ki67 and MNF116 it appeared that there was a greater difference in the requesting pattern between histopathologists for these two antibodies.
CONCLUSION: The rate of use of IHC in our centre seems compatible with that of an academic centre. Personal preferences of the histopathologists, rather than years of postgraduate specialist experience appeared to influence the rate of usage and choice of antibodies.
PURPOSE: To investigate the utility of diffusion tensor imaging (DTI) in determining the microstructural integrity of sciatic and peroneal nerves and its correlation with the MRI grading of muscle atrophy severity and clinical function in CMT as determined by the CMT neuropathy score (CMTNS).
STUDY TYPE: Prospective case-control.
SUBJECTS: Nine CMT patients and nine age-matched controls.
FIELD STRENGTH/SEQUENCE: 3 T T1 -weighted in-/out-of phase spoiled gradient recalled echo (SPGR) and DTI sequences.
ASSESSMENT: Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) values for sciatic and peroneal nerves were obtained from DTI. Muscle atrophy was graded according to the Goutallier classification using in-/out-of phase SPGRs. DTI parameters and muscle atrophy grades were compared between CMT and controls, and the relationship between DTI parameters, muscle atrophy grades, and CMTNS were assessed.
STATISTICAL TESTS: The Wilcoxon Signed Ranks test was used to compare DTI parameters between CMT and controls. The relationship between DTI parameters, muscle atrophy grades, and CMTNS were analyzed using the Spearman correlation. Receiver operating characteristic (ROC) analyses of DTI parameters that can differentiate CMT from healthy controls were done.
RESULTS: There was a significant reduction in FA and increase in RD of both nerves (P
METHODS: A total of 234 invasive cervical carcinomas (152 squamous cell carcinomas, 61 adenocarcinomas and 21 adenosquamous carcinomas) and 16 cervical intraepithelial neoplasia (CIN) I, six CIN II and 25 CIN III were immunohistochemically studied for p53.
RESULTS: p53 was detected more frequently in CIN and invasive carcinoma (100% of CIN I, 74.2% CIN II + III and 70.1% invasive carcinoma) compared with benign cervices (P< 0.001); however, only three squamous cell carcinomas, 11 adenocarcinomas and two adenosquamous carcinomas exhibited p53 expression in >75% of tumour nuclei. Six of the 11 adenocarcinomas and both adenosquamous carcinomas were poorly differentiated compared with one of the three squamous carcinomas. p53 immunoreactive cells were randomly distributed in invasive carcinoma, confined to the lower third of the epithelium in CIN I, reached the middle third in 20% of CIN II and upper third in 16.6% of CIN III.
CONCLUSIONS: Assuming that p53 immunoreactivity indicates gene mutation when the majority (> 75%) of neoplastic cells express p53, p53 mutations would seem uncommon in cervical carcinogenesis. Nonetheless, glandular malignancies, in particular poorly differentiated variants, may show a higher frequency of mutation. p53 was detected more frequently in CIN I compared with CIN II/III and invasive carcinoma which may be due to p53 protein degradation following interaction with high risk human papillomavirus E6 protein in CIN II/III and invasive carcinoma.
METHODS: This is a retrospective observational study of NSCLC patients with sensitising EGFR mutation experiencing disease progression (PD) whilst on first- or second-generation EGFR-TKIs with subsequent investigations to detect acquired T790M mutation at the University of Malaya Medical Centre from 1st January 2015 to 31st December 2017.
RESULTS: A total of 87 patients were included. Upon PD, acquired T790M mutation was found in 55 (63.2%) patients and was significantly more common in patients who achieved partial response (PR) whilst on the EGFR-TKIs (p = 0.008) or had new lung metastasis upon PD (p = 0.048). It was less frequent in patients who developed new symptomatic brain lesions (p = 0.021). Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (p = 0.077). Multivariate analysis revealed PR whilst on EGFR-TKI treatment was an independent predictor of acquiring T790M mutation (p = 0.021), whereas development of new symptomatic brain lesions (p = 0.034) or new lymph node metastases (p = 0.038) upon PD was independently against acquiring T790M mutation. Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (odds ratio: 2.3, 95% confidence interval: 0.84-6.25, p = 0.104).
CONCLUSION: The best tumour response of PR to first- or second-generation EGFR-TKI treatment independently predicts acquired T790M mutation. Patients with exon 19 deletion are likely to acquire T790M mutation. This would prove useful for clinicians to prognosticate and plan subsequent treatments for patients with advanced NSCLC harbouring EGFR mutations.