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

Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer (BC) has been well established, and tumor-infiltrating lymphocytes (TILs) have emerged as a predictive and prognostic biomarker for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer (TNBC) and HER2-positive breast cancer. How computational assessment of TILs can complement manual TIL-assessment in trial- and daily practices is currently debated and still unclear. Recent efforts to use machine learning (ML) for the automated evaluation of TILs show promising results. We review state-of-the-art approaches and identify pitfalls and challenges by studying the root cause of ML discordances in comparison to manual TILs quantification. We categorize our findings into four main topics; (i) technical slide issues, (ii) ML and image analysis aspects, (iii) data challenges, and (iv) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns, or design choices in the computational implementation. To aid the adoption of ML in TILs assessment, we provide an in-depth discussion of ML and image analysis including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial- and routine clinical management of patients with TNBC

The tale of TILs in breast cancer : a report from the International Immuno-Oncology Biomarker Working Group

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed deathligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.The National Health and Medical Research Council of Australia; the Cure; the Royal Australasian College of Physicians; the NIH/NCI ; the National Breast Cancer Foundation of Australia Endowed Chair; the Breast Cancer Research Foundation, New York and the Breast Cancer Research Foundation (BCRF).www.nature.com/npjbcanceram2022Immunolog

Ko-pengekspresan reseptor estrogen beta (ERβ) dan aktin otot licin pada tumor filodes di payudara: suatu kajian tisu mikroarai

Proliferasi tumor filodes tertumpu terutama pada bahagian stroma yang dianggap sebagai komponen neoplastik bagi tumor filodes. Reseptor Estrogen (ER) yang memainkan peranan dalam payudara neoplastik juga terlibat dalam perkembangan tumor filodes. ERβ adalah satu jenis klon ER yang dilaporkan hadir pada stroma tumor payudara manakala pengekspresan aktin otot licin (SMA) di stroma dapat membandingkan gred histologi tumor filodes. Kami membandingkan pengekspresan ERβ dengan SMA pada komponen stroma tumor filodes menggunakan teknik tisu mikroarai (TMA). TMA dibentuk ke atas 77 kes tumor filodes (46 benigna, 17 pinggiran dan 14 malignan) menggunakan jarum berdiameter 0.6 mm (Alphelys Plaisir, Perancis) dan pewarnaan imunohistokimia dijalankan menggunakan penanda molekul ERβ dan SMA. Tumor filodes kerap hadir pada wanita berusia lebih daripada 40 tahun dengan tumor filodes benigna menunjukkan median umur pesakit paling rendah (p=0.017). Ekspresi ERβ dalam komponen stroma meningkat dengan gred histologi tumor. Sementara SMA menunjukkan ekspresi pada 62.8, 41.2 dan 57.1%, masing-masing bagi tumor filodes benigna, pinggiran dan malignan. Kedua-dua ERβ (p=0.024) dan SMA lebih cenderung hadir pada wanita ≥40 tahun. Kajian menunjukkan hubungan signifikan antara ko-pengekspresan ERβ dan SMA (p=0.047) dan 65.5% daripadanya adalah wanita berumur lebih daripada 40 tahun. Ekspresi SMA yang tinggi pada stroma tumor filodes benigna mungkin menunjukkan potensi proliferasi tumor ini untuk menjadi malignan. Ekspresi tinggi ERβ dengan tumor filodes malignan dan hubungannya dengan SMA mencadangkan ko-pengekspresan kedua-dua penanda molekul ini mungkin berperanan dalam tumorigenesis stroma tumor filodes

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

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

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

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