Single-nucleotide polymorphisms and mRNA expression of CYP1B1 influence treatment response in triple negative breast cancer patients undergoing chemotherapy.

Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 (CYP1B1) is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), CYP1B1 142 C>G, 4326 C>G and 4360 A>G, and CYP1B1 mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. CYP1B1 SNPs genotyping (76 TNBC patients) was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods and mRNA expression of CYP1B1 (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 4326C>G polymorphism showed significantly higher risk for development of resistance to chemotherapy with adjusted odds ratio (OR): 6.802 and 3.010, respectively. Whereas, CYP1B1 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. CYP1B1 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of CYP1B1 was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, CYP1B1 expression was found to be significantly upregulated (3.256) in cancerous tissues of patients who did not respond as opposed to those of patients who showed response to chemotherapy. Our findings suggest that SNPs together with mRNA expression of CYP1B1 may be useful biomarkers to predict chemotherapy response in TNBC patients.

CD40 polymorphism in cervical carcinoma in a subset of Malaysian population.

AIM: The aim of this study was to determine the allelic frequency of single nucleotide polymorphisms (SNPs) in the human CD40 gene in cervical cancer. METHODS: A total of 200 cases were selected from the records of the Department of Pathology, Hospital Tuanku Jaafar, Seremban, Malaysia. The samples were collected in three separate groups: cervicitis (n = 61), cervical intraepithelial neoplasia (n = 69), and cervical carcinoma (n = 70). The patients' demographic data and the respective paraffin-embedded tissue samples from Hospital Tuanku Jaafar, Seremban were obtained upon consent. The sample tissues were submitted for DNA extraction using G-spin Total DNA Extraction Kit. DNA obtained was then submitted for nested PCR before restriction enzyme digestion. RESULTS: SNP rs1883832 showed higher prevalence of T alleles in the cervical carcinoma group compared to the control groups and in rs3765459, a higher prevalence of G alleles in the cervical carcinoma group was noted. The results of rs1800686 and rs4810485 were insignificant. CONCLUSION: The data from our study indicates a potential association between the rs1883832 and rs3765459 CD40 gene polymorphism and susceptibility to cervical cancer.

Histomorphology and Immunohistochemistry of Gastrointestinal Stromal Tumors in a Malaysian Population.

PURPOSE: To study histomorphological and immunohistochemical patterns of gastro-intestinal stromal tumours (GISTs) in Malaysia. MATERIALS AND METHODS: A total of 29 GIST cases from Hospital Tuanku Ja'afar, Seremban ,were studied retrospectively over a period of 10 years from January 2002 to December 2011. Patient demographic data like age, sex and etnicity were collected. Tumour characteristics like site, maximum dimension and specimen type were analysed. Evaluation was according to established criteria into very low, low, intermediate and high-risk categories. Immunohistochemical characteristics were also analysed. RESULTS: The mean age of patients was 59.7 years. Males (59%) were found to be more commonly affected than females (41%). The Chinese (45%) were commonly affected than Malays (41%), and Indians (10%). The most common symptom was pain in the abdomen (13.8%). More than half of the cases were seen in stomach (53%). The tumour size ranged from 1.5 cm to 17 cm with a mean of 6.94cm. Microscopic findings revealed that the spindle cell type was the most common (76%). It was observed that the majority of the cases (48%) were categorised in the intermediate risk group. Immunohistochemical staining showed positivity for CD117 (78.6%), CD34 (71.4%), vimentin (86.2%), S-100 (27.6%), SMA (35.7%), PKC THETA (46.4%) and PDGRFA (67.9%).

Expression of P16 in high-risk human papillomavirus related lesions of the uterine cervix in a government hospital, Malaysia.

BACKGROUND: Cervical cancer is one of the most common cancers affecting women worldwide. It is well established that human papilloma virus (HPV) infection is the prime risk factor in the development of cervical cancer. The current screening and diagnostic tests have limitations in identifying the range of lesions caused by HPV. The current study aims to evaluate the diagnostic value of p16 immunohistochemical (IHC) investigation in high-risk human papillomavirus (HR-HPV) related lesions of the uterine cervix in Hospital Tuanku Jaafar, Seremban, Malaysia. METHODS: A total of 75 cases were selected from the records of Pathology services, Hospital Tuanku Ja'afar, Seremban. The samples were collected in three separate groups (n=25 per group) as Carcinoma cervix, Carcinoma in situ and Chronic cervicitis. The demographic data of the patients and the representative paraffin blocks were retrieved from Hospital Tuanku Ja'afar, Seremban. The immunohistochemical staining with p16 and HPV 16 L1 were done on all cases. The staining intensity and density were observed and compared among the three groups of cases. RESULTS: Immunohistochemistry of p16INK4A staining shows nil (0/25) expression in the cervicitis patients, 72% (18/25) in CIN patients and 100% (25/25) in cervical carcinoma. HPV 16 L1 was positive in 100% (25/25) of cervicitis patients, 96% (24/25) of CIN patients and 40% (10/25) of cervical cancers patients. A chi square test was used to analyze the result and the obtained p value was <0.05. CONCLUSION: p16 expression was strongly observed in cervical cancer and minimally observed in cervicitis. Thus indicating p16 immunohistochemistry investigations can aid in diagnosing the different categories of cervical lesions into benign, insitu and malignant. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_202.