OBJECTIVES: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC.
MATERIALS AND METHODS: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records.
RESULTS: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC.
CONCLUSIONS: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.
METHODS: In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival.
RESULTS: The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%).
CONCLUSIONS: Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125 .).
Report: A 58 year old man developed an AVM mimicking a vascular tumour within his left brachioradialis muscle 10 years after a nephrectomy for RCC. Ultrasound and magnetic resonance imaging did not reveal any suspicious features of the vascular lesion.The lesion was successfully removed surgically, and was later proven histopathologically to be metastatic RCC. Further imaging showed widespread metastatic disease, and the patient survived only 15 months after receiving tyrosine kinase inhibitor therapy.
Discussion: This case report aims to highlight a few important points: RCC metastases may be hypervascular, mimicking an AVM. A long disease free interval does not necessarily exclude recurrence or metastasis, as in this case, therefore long term surveillance is recommended. A high index of suspicion must be maintained to avoid delay in treatment, and biopsy of any suspicious lesion for histological examination is mandatory, albeit after many years of cancer remission. Whole body imaging with computed tomography or positron emission tomography computed tomography may detect clinically occult recurrence or metastases, and is important to guide further treatment.
CASE REPORT: A 34-year-old woman with intractable epigastric pain was referred to have repeated endoscopy with biopsy. She was found to multiple gastric erosions and nodules that were diagnosed as inflammatory lesions both endoscopically and histologically. Meanwhile, she developed an acute onset of severe back pain associated with a pathologic compression fracture in the T3 thoracic vertebral body. Imaging studies disclosed a disseminated systemic disease involving abdominopelvic lymph nodes and cervical and thoracic vertebral bodies. The needle biopsy of the pelvic lymph node disclosed diffuse proliferation of monomorphic small round cells that were diffusely positive for CD30 and ALK. A diagnosis of ALK+ ALCL with a monomorphic SC pattern was rendered.
DISCUSSION: A retrospective review of the gastric biopsies with the aid of immunohistochemistry enabled us to recognise the presence of lymphomatous infiltrates with a mixed LH and SC pattern in every piece of gastric biopsies that were repeatedly misdiagnosed as inflammatory lesions. This case illustrates a significant diagnostic pitfall of the LH- and SC-patterns in ALK+ ALCL, in which the tumour cells featuring lymphoid, plasmacytoid or histiocytoid appearance can be masqueraded as inflammatory cells.
Purpose: To study EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort to determine the possibility of using anti-EGFR combinatorial therapy for this population.
Patients and methods: In this study, we evaluated 58 cases of Malaysian TNBC patient samples for EGFR gene copy number alteration and EGFR protein overexpression using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) methods, respectively.
Results: EGFR protein overexpression was observed in about 30% while 15.5% displayed high EGFR copy number including 5.17% gene amplification and over 10% high polysomy. There is a positive correlation between EGFR protein overexpression and gene copy number and over expression of EGFR is observed in ten out of the 48 low copy number cases (20.9%) without gene amplification.
Conclusion: This study provides the first glimpse of EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort emphasising the need for the nationwide large scale EGFR expression evaluation in Malaysia.
METHODS: This is a cross-sectional study of adult CML patients (citizen) in a single but representative centre in southern Sarawak.
RESULTS: Total 79 patients (Malay 39%, Chinese 30.4%, Iban 17.7%, Bidayuh 12.7%) were identified from the databases. Median age at diagnosis was younger, 40, compared to developed countries due to population structure. M:F ratio was higher, 2.6:1 compared to other countries 1.3-1.7:1. Majority presented at chronic phase (89.5%), low/intermediate risk score (80%) and started imatinib (96%) as first line tyrosine kinase inhibitor (TKI), which 40% of them switched to other TKI due to intolerance (17%) and failure (including disease progression)/not achieving major molecular response (83%). Quantitative polymerase chain reaction (qPCR) assessment after three months of TKI treatment had higher positive predictive value to predict Imatinib failure, 75%, than qPCR assessment after six months of TKI treatment, 58%. Presenting phase, symptoms, signs and laboratory data were like most countries. Estimated prevalence and incidence of CML in southern Sarawak was 69.2/1,000,000 population at the Year 2016 (similar to most developing countries) and 8.0/1,000,000 population per year at the Year 2011-2016 (similar to most countries), respectively. The incidence increased with age and was lowest among Iban, 12.8 and highest among Chinese, 19.5, which was 4x higher than Chinese in China. The prevalence of different BCR-ABL1 transcript type was like other Asia countries CONCLUSION: Significant epidemiological differences on M:F ratio and ethnic groups compared to other countries warrant further study.