High CD4+/CD8+ Intratumour Ratio is associated with favourable outcome in triple-negative Breast Cancer

Triple-negative breast cancer (TNBC) is a heterogenous breast cancer subtype which accounts for 10-15% among all diagnosed breast cancers. There is increased resistance of TNBC to conventional chemotherapy and hormonal therapy due to lack of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression. Mutual relationship and interactions between both CD4+ and CD8+ T lymphocytes are very crucial for eliciting adaptive immune system during anti-cancer immune response. This study aimed to determine the ratio of CD4+ and CD8+ T lymphocytes in TNBC by immunohistochemistry assay and to investigate the association of CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) with survival outcome. Quantification of both immunostaining TILs subset was done using conventional light microscope. A wide range of CD4+ and CD8+ TILs subset was found within intratumor stroma of TNBC with population mean score of 0.93 and 0.53, respectively. However, the difference of mean population between both TILs subsets was insignificant overall (P-value of CD4+= 0.484; CD8+= 0.835) when compared statistically using independent t-test. The ratio of CD4+/CD8+ in intratumor stroma ranged from 0.50-5.88 among all TNBC subtypes. The high CD4+/CD8+ ratio within intratumor stroma showed favorable association with survival outcome during the 2 years’ follow-up

Primary Bone Marrow Lymphoma with Secondary Central Nervous System Involvement: a case report

Primary bone marrow lymphoma (PBML) is a rare condition. Most PBMLs are B-cell non-Hodgkin lymphomas (NHLs), where predominated by the diffuse large B-cell lymphomas (DLBCLs). Non-Hodgkin lymphomas affects extranodal sites in one-third of cases. Secondary central nervous system lymphoma (SCNSL) is a rare state which is defined as secondary central nervous system (CNS) involvement in patients with systemic lymphoma. In this report, we described a case of primary bone marrow lymphoma with secondary involvement of the CNS. Patient presented with neurological deficit. Peripheral blood film showed presence of abnormal mononuclear cells. Histopathological examination of the brain tissue showed features of DLBCL with CD10 positivity. Bone marrow examination showed presence of lymphoma cells. He was commenced with Rituximab, methotrexate, vincristine and procarbazine (R-MPV). However, he succumbed after two cycles of chemotherapy

Expression of p40 immunohistochemistry in non-small cell lung carcinoma

Introduction: Lung cancer is the third most common cancers worldwide and in Malaysia. With the major advances in molecular testing of lung cancers and introduction of targeted therapies, the distinction between adenocarcinoma and squamous cell carcinoma (SCC) and its pathologic subtyping becomes important. Recent studies showed that p40 is highly specific for squamous and basal cells, and superior to p63 for the diagnosis of lung SCC. This study aimed to evaluate the use of p40 immunohistochemistry in diagnosis of non-small cell lung carcinoma and its potential to replace current p63 antibody as the best immunohistochemical squamous marker. Methods: Seventy formalin-fixed paraffin-embedded cases previously diagnosed primary lung SCC (n=35) and lung adenocarcinoma (n=35) from January 2008 to December 2016 were retrieved from Department of Pathology, Universiti Kebangsaan Malaysia. We compared the results of tumour cells immunoreactivity for p40 and p63 antibodies in lung SCC and lung adenocarcinoma. Results: The p40 was positive in 29 cases of previously diagnosed lung SCC (82.8%) and two cases of lung adenocarcinoma (5.7%). The p63 was positive in 31 lung SCC (88.6%) and 22 of lung adenocarcinoma (62.9%). The reactivity for both p40 and p63 in lung SCC was strong and diffuse whereas the reactivity of both antibodies in lung adenocarcinoma is variable. Conclusions: We found that the expression of p40 is equivalent to p63 in lung SCC, but p40 is an excellent marker in distinguishing lung SCC from adenocarcinoma. We suggest that p40 is considered for routine use and replace p63 as lung SCC marker

Array comparative genomic hybridization analysis identified the chromosomal aberrations and putative genes involved in prostate tumorigenesis of Malaysian men

The identification of chromosomal aberrations in prostate cancer has been widely studied with several known oncogenes and tumor suppressor genes have successfully been discovered. The most frequent aberrations detected in western population were losses in chromosome 5q, 6q, 8p, 13q, 16q, 17p, 18q and gains of 7p/q and 8q. The purpose of this study was to determine the chromosomal aberrations among Malaysian men of Southeast Asia population and discover those potential genes within that chromosomal aberrant region. Thirty-six formalin-fixed paraffin embedded specimens consist of eight organ-confined prostate cancer cases, five with capsular invasion, 14 showed metastasis and nine cases had no tumor stage recorded, were analyzed by array CGH technique. Chromosomal losses were frequently detected at 4q, 6q, 8p, 13q, 18q while gains at 7q, 11q, 12p, 16q and 17q. Gain of 16q24.3 was statistically significant with tumor size. Gains of 6q25.1 and Xq12 as well as losses of 3p13-p1.2 and 13q33.1-q33.3 were significantly correlated with Gleason grade whereas 12p13.31 gain was associated with bone metastasis. Several potential genes have also been found within that aberrant region which is myopodin (4q26-q27), ROBO1 (3p13-p11.2), ERCC5 (13q33.1-q33.3) and CD9 (12p13.31), suggesting that these genes may play a role in prostate cancer progression. The chromosomal aberrations identified by array CGH analysis could provide important clues to discover potential genes associated with prostate tumorigenesis of Malaysian men

Lymphovascular Invasion is a Significant Prognostic Marker of Distant Metastasis in Breast Carcinoma

Lymphovascular invasion (LVI) is not incorporated in most staging systems although assessment of LVI is now part of the minimum data set for breast carcinoma pathology reporting. This study investigates the correlation between LVI with clinical staging, grading and prediction of patients’ survival in patients with invasive breast carcinoma. This was a retrospective study using data obtained from reviewing archival histological material and patients’ medical records at Queen Elizabeth Hospital, Sabah, Malaysia. Breast carcinoma samples from 117 female patients at all stages of disease were included in this study. Correlation was performed between LVI and staging, grading, lymph node (LN) status and patient’s clinical outcome after five years of diagnoses. LVI showed significant correlation with LN involvement and distant metastasis but no significant correlation between LVI and grading. LVI correlates with clinical staging and is a reliable predictor of outcome in patients with invasive breast carcinoma

Identification of Y chromosomal material in turner syndrome by Fluorescence in Situ Hybridisation (FISH)

Turner syndrome is one of the most common chromosomal abnormalities affecting newborn females. More than half of patients with Turner syndrome have a 45X karyotype. The rest of the patients may have structurally abnormal sex chromosomes or are mosaics with normal or abnormal sex chromosomes. Mosaicism with a second X sex chromosome is not usually of clinical significance. However, Turner syndrome patients having a second Y chromosome or Y chromosomal material are at risk of developing gonadoblastoma later in life. The aim of this study is to compare the results of conventional (karyotyping) and molecular cytogenetics (FISH), and discuss the advantages and limitations in the diagnosis of Turner syndrome. We also aim to compare the degree of mosaicism identified using conventional cytogenetics and FISH techniques. Conventional cytogenetics and FISH analyses were performed on eight peripheral blood samples of patients with Turner syndrome collected between 2004 and 2006. From this study, two out of eight patients with Turner syndrome were found to have the sex determining region on the Y chromosome (SRY) gene by FISH analysis. Our results showed that the rate of detection of mosaic cases in Turner syndrome was also increased to 88% after using the FISH technique. We concluded that FISH is more superior to conventional cytogenetics in the detection of the Y chromosomal material. FISH is also a quick and cost effective method in diagnosing Turner syndrome and assessing the degree of mosaicis

Predicting Prognosis and Platinum Resistance in Ovarian Cancer: Role of Immunohistochemistry Biomarkers

Ovarian cancer is a lethal reproductive tumour affecting women worldwide. The advancement in presentation and occurrence of chemoresistance are the key factors for poor survival among ovarian cancer women. Surgical debulking was the mainstay of systemic treatment for ovarian cancer, which was followed by a successful start to platinum-based chemotherapy. However, most women develop platinum resistance and relapse within six months of receiving first-line treatment. Thus, there is a great need to identify biomarkers to predict platinum resistance before enrolment into chemotherapy, which would facilitate individualized targeted therapy for these subgroups of patients to ensure better survival and an improved quality of life and overall outcome. Harnessing the immune response through immunotherapy approaches has changed the treatment way for patients with cancer. The immune outline has emerged as a beneficial tool for recognizing predictive and prognostic biomarkers clinically. Studying the tumour microenvironment (TME) of ovarian cancer tissue may provide awareness of actionable targets for enhancing chemotherapy outcomes and quality of life. This review analyses the relevance of immunohistochemistry biomarkers as prognostic biomarkers in predicting chemotherapy resistance and improving the quality of life in ovarian cancer

Predicting Prognosis and Platinum Resistance in Ovarian Cancer: Role of Immunohistochemistry Biomarkers

Ovarian cancer is a lethal reproductive tumour affecting women worldwide. The advancement in presentation and occurrence of chemoresistance are the key factors for poor survival among ovarian cancer women. Surgical debulking was the mainstay of systemic treatment for ovarian cancer, which was followed by a successful start to platinum-based chemotherapy. However, most women develop platinum resistance and relapse within six months of receiving first-line treatment. Thus, there is a great need to identify biomarkers to predict platinum resistance before enrolment into chemotherapy, which would facilitate individualized targeted therapy for these subgroups of patients to ensure better survival and an improved quality of life and overall outcome. Harnessing the immune response through immunotherapy approaches has changed the treatment way for patients with cancer. The immune outline has emerged as a beneficial tool for recognizing predictive and prognostic biomarkers clinically. Studying the tumour microenvironment (TME) of ovarian cancer tissue may provide awareness of actionable targets for enhancing chemotherapy outcomes and quality of life. This review analyses the relevance of immunohistochemistry biomarkers as prognostic biomarkers in predicting chemotherapy resistance and improving the quality of life in ovarian cancer

iPS cell transplantation in a mouse model – A semiquantitative assessment

This study was carried out to determine the effectiveness of induced pluripotent stem (iPS) cell-transplantation as a therapy on wound healing using a splinted wound mouse model. Eighteen clinically healthy female mice were treated with 1μg/g of dexamethasone intramuscular injection once a day for three consecutive days to induce immunosuppression. Under anaesthesia, two sterile wounds were made on shaved backs of each mouse via biopsy punch. With a gap of 20 mm in-between, six injections were delivered once, around the two wounds before the wounds were adhered with splints and wound dressing. The mice were divided into two groups; Group A was given 7 × 105 iPS cells in each injection, and while Group B were injected with 0.9% sodium chloride instead. Wound closure rates were determined through timed scaled photography and analyses with GNU Image Manipulation Program. Three mice from each group were euthanised every 7 days post-wounding, immediately after which wound beds and blood were harvested. Wound beds were fixed, processed, blocked, and sectioned. Sections were stained with H&E; Masson's Trichrome; and immunolabeled for CD31 and CD68; and then examined under a compound microscope subjected to a scoring scheme. From this semiquantitative assessment, Group A sections scored better in angiogenesis on day 7 (p = 0.057), a vital process in the proliferation stage, and hypodermis regeneration on day 21 (p = 0.006), which suggests the wound healing is complete. Together, these findings suggest Group A was ahead in the process of wound healing; although results from lymphocyte count, fibroblast count, granulation tissue, collagen, and wound closure were not statistically significant

Endometrial Heparin-Binding Epidermal Growth Factor Gene Expression and Hormone Level Changes in Implantation Window of Obese Women with Polycystic Ovarian Syndrome

Introduction: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder amongst reproductive-age women, and 61% to 76% of women with PCOS are obese. Obese women with PCOS are usually burdened with infertility problems due to implantation failure. Thus, progesterone treatment is usually used to improve implantation rates. Although Hb-EGF expression is actively involved in endometrial receptivity and implantation, the data on heparin-binding epidermal growth factor (Hb-EGF) expression following progesterone therapy in obese women with PCOS are still lacking. Objective: To investigate the changes in serum follicle-stimulating hormone (FSH), luteinising hormone (LH), dehydroepiandrosterone sulphate (DHEA), progesterone and oestradiol levels and Hb-EGF expression in obese women with PCOS during the implantation window following progesterone therapy. Method: A total of 40 participants aged 18–40 years old were recruited following the provision of written consent. The participants were divided into the obese PCOS, normal-weight PCOS, obese fertile and normal-weight fertile groups. First blood collection was done before ovulation. Then, daily oral micronised progesterone (Utrogestan 200 mg) was given to the PCOS group for 10 days. The treatment was followed by a second blood collection and endometrial tissue sampling by using a Pipelle de Cornier catheter. In the fertile group, ovulation was confirmed by using ultrasound, and a second blood sample was collected on days 7 to 9 postovulation. The serum levels of FSH, LH, DHEA, progesterone and oestradiol were measured in all participants. Wilcoxon signed-rank test was used to compare FSH, LH, DHEA, progesterone and oestradiol levels during pre- and postovulation. Mann–Whitney test was performed to compare FSH, LH, DHEA, progesterone and oestradiol levels between two groups: (1) the PCOS group and the fertile group, (2) the obese PCOS group and the non-obese PCOS group and (3) the obese group and the non-obese fertile group. Result: Serum FSH levels were lower in obese women in their follicular phase than in women with normal weight regardless of their PCOS status, whereas serum LH/FSH ratios and DHEA levels were higher in women with PCOS than in women without PCOS. However, endometrial Hb-EGF expression was lower in the obese PCOS group than in the normal-weight PCOS group. Conclusions: Different patterns of hormonal levels and Hb-EGF expression levels were seen between the studied groups. However, further in vitro and in vivo studies are needed to investigate the mechanism underlying the changes in FSH, LH/FSH ratio, DHEA and Hb-EGF expression in PCOS after progesterone treatment