Synchronous Breast and Cervical Carcinoma: A Genetic Point of View.

Breast carcinoma is the most common cancer of women in Malaysia. The most common sites of metastasis are the lung, liver, bone and brain. A 45-year-old lady was diagnosed with left invasive breast carcinoma stage IV (T4cN1M1) with axillary lymph nodes and lung metastasis. She was noted to have a cervical mass through imaging, and biopsy showed CIN III. Post chemotherapy, the patient underwent left simple mastectomy with examination under anaesthesia of the cervix, cystoscopy and staging. The cervical histopathological examination (HPE) showed squamous cell carcinoma, and clinical staging was 2A. The breast tissue HPE showed invasive carcinoma with triple receptors positivity. The patient was given tamoxifen and put on concurrent chemoradiotherapy (CCRT) for the cervical cancer. The management of each pathology of this patient involved a multi-disciplinary team that included surgeons, oncologists, gynaecologists, pathologists and radiologists. Due to the complexity of the case with two concurrent cancers, the gene expression profiles may help predict the patient's clinical outcome.

First-trimester miscarriage in the background of endometrial carcinoma.

BACKGROUND: Endometrial cancer in young women (less than 40-year-old) is associated with anovulatory menses, polycystic ovarian syndrome (PCOS) and subfertility. Endometrial cancer occurring in a miscarriage is rare. We highlight a case of endometrial cancer occurring during miscarriage of a non-viable pregnancy, its management and the outcome. CASE: A 32-year-old woman, Gravida 1 Para 0, was referred to our center at 7 weeks gestation in 2018 for uncontrolled diabetes mellitus diagnosed during investigation for subfertility. Her poor compliance with the treatment is consistent with an HbA1c of 8%. During the assessment, she was already complaining of lower abdominal pain. Ultrasound showed irregular IUGS with no fetal echo. She had a miscarriage soon; however, due to ultrasound evidence of thickened and irregular endometrium (17 mm) with mixed echogenicity, dilatation and curettage (D + C) were commenced. The first and second tissues were reported as the product of conception (POC) and well differentiated endometrioid adenocarcinoma, respectively. The first hysteroscopy showed foci area of polypoidal growth at the right posterior endometrium, obscuring the right ostium, with similar histology report. She was commenced on high-dose progestogen with hysteroscopy surveillance 6 months later, which showed disease regression. After two normal hysteroscopies and endometrial biopsies with continuous progestogen therapy for 12 months, cyclical progestogen for 12 months and follow-up for another 6 months, she had spontaneous conception and is currently pregnant at 16 weeks gestation. CONCLUSION: Endometrial cancer should be suspected in high-risk patients with first-trimester miscarriage. Individualized treatment with high dose progestogen and follow-up with the proper patient and partner counselling and education has high successful regressionand later on, pregnancy rate.

Conservative management of Retzius space hematoma following spontaneous vaginal delivery in a woman with an unscarred uterus: A case report.

Introduction: A retroperitoneal hematoma in obstetrics is very rare following spontaneous vaginal delivery. It requires a high index of suspicion, especially in a hemodynamically unstable patient with no active bleeding or external trauma postpartum, as early intervention is needed to prevent maternal morbidity and mortality. Conservative management may be an appropriate strategy in managing large hematomas even though surgical evacuation is classically recommended. Case: We report the case of a 39-year-old woman, para three, with a hematoma of the Retzius space after spontaneous uncomplicated vaginal delivery. The patient had sudden abdominal pain associated with urinary retention, two hours after delivery. She had a palpable mass at the anterior upper part of the vaginal wall, near the fornices, but no abnormality was detected at the labia majora, labia minora and lower part of the vagina. A transabdominal ultrasound scan revealed a mixed-echogenicity mass between the bladder and lower part of the uterus measuring 110 × 90 × 60 mm. The patient's hemoglobin level dropped from 12 g/dL to 10 g/dL. Given the patient's clinically stable state, she was managed conservatively with antibiotics, analgesics and one unit of packed red blood cells, and was discharged home day 5 postpartum. Conclusion: This case supports the conservative management of even large Retzius space hematomas for hemodynamically stable patients. A high index of suspicion and thorough evaluation are required when encountering a complaint of urinary retention and abdominal pain postpartum.

Oncologist-led BRCA counselling improves access to cancer genetic testing in middle-income Asian country, with no significant impact on psychosocial outcomes.

BACKGROUND: Identifying patients with BRCA mutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming. METHODS: The Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer. RESULTS: Oncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1 or BRCA2, and there was no difference between psychosocial measures for carriers in both arms. CONCLUSION: The MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing.

ADAM9 Expression in Uterine Cervical Cancer and Its Associated Factors

Background: Cervical cancer is a preventable disease caused by human papillomaviruses. It is the third most common cancer to occur in women of reproductive age. The ADAM9 protein plays a role in basement membrane degradation and tumour metastasis in certain types of tumour. Thus, it has the potential to become a new targeted therapy. The objective of this study was to investigate ADAM9 expression in cervical cancer and to determine the factors associated with ADAM9-positive expression. Methods: This cross-sectional study was conducted in Hospital Universiti Sains Malaysia (HUSM) Kelantan, Malaysia from December 2010 to December 2012. Histological slides obtained from 95 cervical cancer cases diagnosed and/or treated in HUSM from 2000 to 2010 were analysed. The ADAM9 immunostain was then performed on the paraffin blocks. The statistical data entry and analysis were done using SPSS version 18.0. Multiple logistic regression analysis was performed to determine the factors associated with ADAM9-positive expression. Result: Of the 95 cervical cancer patients included in the study, 72 (75.8%) patients showed positive ADAM9 expression. The mean age of the patients was 53.89 (10.83) years old. Squamous cell carcinoma was the most common type of cervical cancer (n = 67, 70.5%). Factors that showed a statistically significant association with ADAM9-positive expression were tumour size (adjusted odds ratio [adj. OR]: 1.08; 95% confidence interval [CI]: 1.02, 1.13; p = 0.004), distant metastasis (adj. OR: 12.82; 95% CI: 1.91, 86.13; p = 0.009) and the histological type of cervical cancer (i.e. squamous cell carcinoma) (adj. OR: 7.39; 95% CI: 1.42, 38.51; p = 0.017). Conclusion: The ADAM9 immunostain was consistently positive in malignant cells. Thus, ADAM9 expression can be used as a prognostic/therapeutic indicator in aiding clinician decision-making regarding patient treatment (targeted therapy).

Prevalence and type distribution of human papillomavirus (HPV) in Malaysian women with and without cervical cancer: an updated estimate.

Information on the prevalence and type distribution of human papillomavirus (HPV) among Malaysian women is currently limited. The present study therefore aimed to provide an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. Total DNA was isolated from the cervical cell specimens of 185 histopathologically confirmed cervical cancer patients and 209 cancer-free healthy females who were tested negative in a recent Pap test. Viral-specific DNA was subsequently amplified with biotinylated primers and hybridized to HPV type-specific probes via a proprietary "flow-through hybridization" process for determination of HPV genotype. It was demonstrated that 83.2% of the cervical cancer patients and none (0.0%) of the cancer-free females were positive for HPV infection. Among HPV-positive subjects, 14 different viral genotypes were observed, namely HPV16, 18, 31, 33, 35, 45, 52, 53, 58, 66/68, 73, 81, 82, and 84/26. A total of 91.6% of the HPV-positive subjects had single-type HPV infections and the remaining 8.4% were simultaneously infected by two HPV genotypes. The most common HPV infections found were HPV16 (35.7%), HPV18 (26.0%), HPV58 (9.1%), and HPV33 (7.1%) single-type infections, followed by HPV16 + HPV18 co-infections (5.2%). The study has successfully provided an updated estimate on the prevalence and type distribution of HPV among Malaysian women with and without cervical cancer. These findings could contribute valuable information for appraisal of the impact and cost-effectiveness of prophylactic HPV vaccines in the Malaysian population.

Identification of Optimal Reference Genes for Normalization of RT-qPCR Data in Cancerous and Non-Cancerous Tissues of Human Uterine Cervix.

This study aimed to identify the most stably expressed reference genes from a panel of 32 candidate genes for normalization of reverse transcription-quantitative real-time polymerase chain reaction data in cancerous and non-cancerous tissues of human uterine cervix. Overall, PUM1, YWHAZ, and RPLP0 were identified as the most stably expressed genes in paired cancerous and non-cancerous tissues. The results were further stratified by the state of malignancy of the tissues, histopathological type of the cancer, and the human papillomavirus-type.

FAS c.-671A>G polymorphism and cervical cancer risk: a case-control study and meta-analysis.

This study aimed to investigate the association between FAS c.-671A>G polymorphism and cervical cancer risk in a case-control setting, followed by a meta-analysis of the published literatures. The case-control study involved genotyping of the polymorphism in 185 histopathologically confirmed cervical cancer patients and 209 cancer-free female controls utilizing PCR-RFLP technique, followed by logistic regression analyses. Meta-analysis was then conducted under homozygous, heterozygous, dominant, recessive and allele contrast models to combine data from 12 studies which consisted of 2798 cases and 3039 controls. Our case-control analysis revealed a significant association of the variant allele (G) and the homozygous variant genotype (GG) of the FAS polymorphism with an increased risk of cervical cancer. Subgroup analysis by ethnicity further confirmed the risk association in Malays (P < 0.05), but not among non-Malays (P > 0.05). However, results of meta-analysis suggested a lack of association between the polymorphism and cervical cancer risk in all the five genetic models analyzed. In conclusion, while the FAS c.-671A>G polymorphism may serve as a biomarker for cervical cancer risk prediction among the Malays, there is a limited usability of the polymorphism as a cervical cancer risk biomarker in other populations.