Kah Teik Chew

Expression of PD-1 and PD-L1 in Endometrial Cancer: Molecular and Clinical Significance

The landscape of diagnosing and treating endometrial cancer is undergoing a profound transformation due to the integration of molecular analysis and innovative therapeutic approaches. For several decades, the cornerstone treatments for endometrial cancer have included surgical resection, cytotoxic chemotherapy, hormonal therapy, and radiation therapy. However, in recent years, the concept of personalised medicine has gained momentum, reshaping the way clinicians approach cancer treatment. Tailoring treatments based on specific biomarkers has evolved into a standard practice in both initial and recurrent therapy protocols. This review aims to provide an in-depth exploration of the current state of molecular analysis and treatment strategies in the context of endometrial cancer, focusing on the immunological aspect of the PD-1/PD-L1 axis. Furthermore, it seeks to shed light on emerging and innovative approaches that hold promise for the future modulation of endometrial cancer treatments. In essence, as researchers delve into the complex molecular landscape of endometrial cancer and harness the understanding of the PD-1/PD-L1 axis, we are paving the way for more targeted, effective, and personalised therapies that have the potential to significantly improve the outcomes and quality of life for patients with this challenging disease.

Giant Ovarian Leiomyoma Mimicking a Malignant Intra-Abdominal Tumor

BACKGROUND Leiomyoma is a benign gynecological neoplasm most commonly seen in the uterus, while primary ovarian leiomyomas are exceptionally uncommon. These tumors can grow to a large size and undergo degenerative changes, including infarction. Large ovarian leiomyomas with a solid-cystic appearance on imaging can closely resemble malignant ovarian neoplasms, leading to diagnostic uncertainty. We present a case of giant ovarian leiomyoma exhibiting clinical and radiological features closely mimicking those of an ovarian malignancy. CASE REPORT A 68-year-old para 4 woman presented with a four-year history of progressive abdominal distension, which had notably increased over the past two years. A computed tomography (CT) scan of the thorax, abdomen, and pelvis (CT-TAP) revealed a well-defined, lobulated, heterogeneously enhancing, solid-cystic mass, predominantly occupying the left lower abdominal quadrant and originating from the right ovary. Tumor marker analysis showed normal levels of CEA and CA19-9 with a mildly elevated CA-125 level of 51 U/ml. The calculated Risk of Malignancy Index (RMI) was 153, raising suspicion for an ovarian malignancy. In light of these findings, the patient was planned for a total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO). The intraoperative findings revealed a right ovarian mass measuring 20×20 cm. Histopathological examination confirmed an ovarian leiomyoma with cystic degeneration. CONCLUSIONS The case report demonstrates the preoperative diagnostic challenges associated with giant ovarian leiomyoma, which can result in an unnecessary radical surgical procedure. This underscores the importance of meticulous preoperative and intraoperative assessment to ensure accurate diagnosis and appropriate management.

Gene expression and soluble protein level of PD-1 and its ligands (PD-L1 and PD-L2) in endometrial cancer

Checkpoint programmed death-1 (PD-1) and programmed cell death ligands (PD-Ls) are negative immunoregulatory molecules that assist tumour cells in evading the immune system. The interaction of PD-1 and PD-Ls inhibits T cells and tumour-infiltrating lymphocytes (TILs) while increasing the function of immunosuppressive regulatory T cells (Tregs). This leads to the evasion of the immune response by tumour cells. The roles of PD-1, PD-L1, and PD-L2 in endometrial cancer (EC) have not been fully elucidated. This study investigates the mRNA gene expression and soluble protein levels of these molecules in EC compared to controls, with detailed analysis of clinical profiles. The results showed that EC had significantly higher mRNA gene expression and soluble protein levels of PD-L1 and PD-L2, but not PD-1. Specifically, PD-1 mRNA gene expression was significantly higher in cases with less than 50% myometrial invasion. Additionally, the soluble protein level of PD-1 was substantially higher in patients under the age of 60. Higher gene expression of PD-L1 was observed only in advanced stages of EC. However, the soluble PD-L1 protein level was significantly elevated in type II EC, advanced stage, higher grade, lympho-vascular space invasion (LVSI), and in cases with myometrial invasion of 50% or more. PD-L2 mRNA gene expression and soluble protein levels significantly differed across all clinical profiles except for LVSI. These findings suggest that PD-1, PD-L1, and PD-L2 may serve as potential predictive biomarkers, which could be beneficial for the management of endometrial cancer patients through immunotherapy.

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.

Perception and knowledge of human papillomavirus (HPV) vaccine for cervical cancer prevention among fully vaccinated female university students in the era of HPV vaccination: a cross-sectional study

Objective To assess the perception and knowledge of cervical cancer prevention among fully vaccinated female university students in the era of human papillomavirus (HPV) vaccination. Design Cross-sectional using a validated questionnaire. Setting Face-to-face interview at a public university in Malaysia. Participants 384 fully vaccinated female students were included in the study. Results The total knowledge score in the questionnaire was 18 and was ranked according to score level into three groups: poor (score ≤5), moderate (score 6–10) and good (score ≥11). Mean score for knowledge of cervical cancer prevention was 8.24 (SD ±3.85), with 170 respondents (44.3%) scoring moderate knowledge level. The mean score for knowledge of HPV infection and its association with cervical cancer was 4.56±2.47, while the mean score for knowledge of HPV vaccination for cervical cancer prevention was 3.68 (SD ±1.98). A total of 186 (48.4%) respondents perceived that regular Pap smear was unnecessary after HPV vaccination. Respondents’ perceived seriousness and susceptibility of HPV infection correlated well with knowledge of cervical cancer prevention. Two main reasons for their acceptance of HPV vaccine were self-health awareness and free vaccination. Conclusion The knowledge of HPV vaccination for cervical cancer prevention was average among vaccinated university students. Many of them had poor knowledge about Pap smear and did not consider regular Pap smear as an important cervical cancer screening tool following HPV vaccination. There is still a need for continued health education to improve the perception and knowledge about HPV infection and cervical cancer prevention among young adults in the community.