Correlation between estrogen receptor and programmed death ligand-1 in type I endometrial cancer.

Objective: To determine the effect of estrogen receptor (ER) on programmed death-ligand 1 (PD-L1) expression in type I endometrial cancer (EC). Material and Methods: This retrospective study included 85 patients with type I EC who underwent surgery at Dr. Soetomo Hospital between 2018 and 2022. A random sampling technique was employed. Immunohistochemistry (IHC) with ER and PD-L1 antibodies was performed on all samples. In this study, ER expression served as the independent variable, while PD-L1 expression was considered the dependent variable. Data analysis was performed using Spearman's rank correlation coefficient test. Results: Out of the 85 patients with type I EC, 58 (68.2%) exhibited positive and 27 (31.8%) exhibited negative ER expression. Meanwhile positive PD-L1 expression was seen in 67 (78.8%) and 18 (21.2%) exhibited negative PD-L1 expression. The study revealed a strong negative correlation between ER and PD-L1 expression in EC (rho value = -0.886, p-value = 0.0001). Conclusion: ER downregulates PD-L1 in type I EC. The findings of this study can be used as reference data and as the basis for further research, especially investigations of the prognostic and immunotherapeutic value of ER and PD-L1 expression in type I EC.

Estrogen receptor and programmed death ligand-1 expression in type 1 endometrial cancer and its associated clinicopathological characteristics.

BACKGROUND: This study aimed to determine the association of estrogen receptor (ER) and programmed death ligand-1 (PD-L1) expression with the clinicopathological characteristics of type 1 endometrial cancer. MATERIALS AND METHODS: A total of 85 patients with type 1 endometrial cancer who underwent surgery at the Dr. Soetomo Hospital, Surabaya, Indonesia were retrospectively studied. Data about the age, menopausal status, body mass index, disease stage, cell differentiation, angiolymphatic invasion, myometrial invasion, and adjuvant therapy of the patients were collected from medical records. Immunohistochemistry with ER and PD-L1 antibodies was performed on all samples. The association between ER and PD-L1 expression and clinicopathological characteristics was statistically analyzed. RESULTS: The positivity rates of ER and PD-L1 in type 1 endometrial cancer were 68.2 % and 78.5 %, respectively. ER positivity was significantly correlated with body mass index (BMI) ≥25, premenopausal status, early stage of disease, <1/2 myometrial invasion, negative nodal metastasis, and lack of adjuvant therapy. It was also associated with age <55 years, low-grade cells, and angiolymphatic invasion, but the correlation was not significant. Meanwhile, PD-L1 positivity was significantly correlated with BMI <25, menopausal status, advanced stage of disease, high-grade cells, angiolymphatic invasion, and adjuvant therapy. It was also associated with age ≥55 years and nodal metastasis, but the correlation was not significant. CONCLUSION: ER and PDL-1 positivity is associated with the clinicopathological characteristics of type 1 endometrial cancer.

Ureteral small cell neuroendocrine carcinoma: A case report and short review.

INTRODUCTION AND IMPORTANCE: Primary small cell neuroendocrine carcinoma (SCNEC) in the urinary tract represents less than 0.5 % of urinary tract cancers, and bladder or prostate are the most common sites. Early diagnosis and treatment of ureteral SCNECs are challenging due to nonspecific clinical symptoms and radiographic findings. CASE PRESENTATION: Here, we described a diagnostic and therapeutic challenge of a 56-yearold male with recurrent right flank pain that did not relieve with analgesics alone. The patient underwent several non-invasive to invasive procedures revealing nonspecific inflammation pathology of the ureter that later developed into protruded papillary mucosa resembling polypoid cystitis. Later, an abdominal multi-slice computed tomography examination suggested a malignant mass and was confirmed as SCNEC from the pathological analysis. After several successful chemotherapy cycles and surgical procedures, cancer reoccurred, and the patient's general condition deteriorated. He passed away a year after a radical cystoprostatectomy and nephroureterectomy on his right side. CLINICAL DISCUSSIONS: The occurrence of primary SCNEC is a highly uncommon phenomenon. As SCNEC arises from pluripotent stem cells that have differentiated into neuroendocrine cells, some patients may exhibit paraneoplastic syndrome. The patient's prognosis of this tumor is poor, even for patients in the earliest phases, because SCNEC is characterized by highly aggressive local invasion and distant metastases. CONCLUSIONS: This case highlights the importance of accurate early diagnosis and treatment of recurrent flank pain and considering the possibility of a malignant tumor as the cause of obstruction.

The MAGE A1-A10 Expression associated with Histopathological Findings of Malignant or Non-Malignant Cells in Peripheral Lung Tumors.

OBJECTIVE: The objective was to evaluate the expression of melanoma antigen (MAGE) A from A1 to 10 (A1-10) and the individual MAGE A family in the peripheral lung tumors and to analyze its association with histopathological findings. METHODS: A cross-sectional study was conducted on 67 samples of peripheral lung tumor obtained by core biopsies from patients with clinical diagnoses such as lung and mediastinal tumors. The specimens were divided into two, one to perform histopathological diagnosis and the last for mRNA MAGE A examination. A Nested polymerase chain reaction (PCR) was performed using universal primer, MF10/MR10 and MF10/MR12. The collected data were analyzed by appropriate statistical techniques. RESULT: The histopathological finding showed 41 (61.2 %) of specimens as malignant cells and 26 (38.8 %) of specimens as non-malignant cells. MAGE A1-10 was expressed at 47 (70.1 %) and MAGE A1-6 was expressed at 25 (37.3 %) of specimens. In a malignant cell, MAGE A1-10 and MAGE A1-6 were expressed at 33 (80.5 %) and 19 (46.3 %), respectively. In non-malignant cells, MAGE A1-10 and MAGE A1-6 were expressed at 14 (53.9 %) and 6 (23.1 %,) respectively. The MAGE A1-10 and MAGE A8 expressions were significantly associated with histopathological findings of malignant or non-malignant cells. The sensitivity, specificity, and diagnostic accuracy of MAGE A1-10 were 80.5 %, 46.2 %, and 67.2 %, respectively; while for MAGE A8 were 41.5 %, 88.5 %, and 59.7 %, respectively. CONCLUSION: The MAGE A1-10 expression was the most commonly detected and associated with the histopathological finding. Moreover, it was more sensitive and specific and had higher diagnostic accuracy than others. Therefore, the MAGE A1-10 assay may improve the accuracy of the diagnosis of malignancy in peripheral lung tumors.

Polymerase chain reaction of human cytomegalovirus from liver and urine compared with serological test in cholestasis infants.

INTRODUCTION: The most common infection in cholestatic infants is caused by human cytomegalovirus (HCMV). The aims were to detect the presentation of HCMV in cholestatic infants and to evaluate the concordance, sensitivity, and specificity between serology and polymerase chain reaction (PCR) of HCMV from liver biopsy and urine specimens. METHODOLOGY: A descriptive observational study with a cross-sectional approach was conducted on 35 cholestatic infants with ethical approval. Specimens were liver biopsy, urine, and anti-HCMV serology. Liver and urine specimens were performed to nested PCR, followed by statistical analysis. RESULTS: PCR from the liver biopsy and urine specimen were positive in 74.3% and 85.7%, respectively. There was no concordance between IgM with the liver PCR, but there was a concordance between IgM with the urine PCR and between IgG with the liver and urine PCR. The sensitivity and specificity of IgM with the liver PCR were 46 % and 56%, respectively, with a diagnostic accuracy of 49%. While IgG sensitivity was 96% with a diagnostic accuracy of 80%. IgG sensitivity and IgM specificity compared with the urine PCR were 93% and 100%, respectively, with a diagnostic accuracy of more than 60%. CONCLUSIONS: It demonstrates a high prevalence of HCMV DNA in urine and liver biopsy from cholestatic infants. HCMV PCR assay is more sensitive and specific than the anti-HCMV IgM, but IgG has high sensitivity and accuracy diagnostic. Therefore, serological examination is an option for diagnosing HCMV infection in cholestatic infants in developing countries with no PCR facilities.

Nigella sativa L. as immunomodulator and preventive effect on renal tissue damage of lupus mice induced by pristane.

Introduction: Nigella sativa L. is an herbal plant with Thimoquinone as the main therapeutic properties. This plants has been shown to cure for various diseases and affected the immune system by modulating cytokines and T regulatory cell (Treg) sot that able to prevent renal injury in several diseases, but studies on Systemic Lupus Erythematous are still rare. Objective: This study aimed to investigate immunomodulation and preventive effects of Nigella sativa L. on renal tissue damage in Pristane induced Lupus (PIL)-mice model. Methods: This true experimental study included 48 female Balb/C mice, 38 mice were injected pristane intraperitoneally and waited 16 weeks to become lupus model. Only 30 mice met the Systemic Lupus International Collaborating Clinics criteria. Ten healthy mice were used as control, 30 PIL mice model divided into 3 groups (placebo, steroid, Nigella sativa L.). At the end of 28 days of treatment, the mice were sacrificed to take a blood sample and kidney organ to evaluate the injury histopathologically. Results: The results showed that the cytokine expression Interleukin (IL) (IL-17, IL-6, IL-23) in the Nigella sativa L. group was the lowest. The highest absolute number of Tregs was the steroid group followed Nigella sativa L. group. Renal injury assessed histopathologically showed the Nigella sativa L. group was the lowest and almost close to normal. Conclusion: This study indicate that Nigella sativa L. has an immunomodulatory effect and can prevent kidney injury PIL-treated mice. We suggest that Nigella sativa L. may need to be considered for further research on its use as a complementary supplement in lupus patients.

p16INK4A Expression in Condyloma Acuminata Lesions Associated with High-Risk Human Papillomavirus Infection.

OBJECTIVE: The objective of this study was to discover the possible correlation between p16INK4A expression and the LR/HR-HPV infection in condyloma acuminate (CA) lesions. MATERIALS AND METHOD: This cross-sectional study was conducted during January-December 2017 on 33 CA patients. The expression of p16INK4A was detected by immunohistochemistry (IHC) staining. The positive interpretation was carried out by scoring which score 0 was negative, score 1 was sporadic, score 2 was focal, and score 3 was diffuses. The HPV genotypes were identified by reverse line blot, and 40 genotypes of HPV detected, including HR-HPV (HPVs 16, 18, 26, 31, 33,35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68a, 68b, 69, 73, and 82) and LR-HPV (HPVs 6, 11, 40, 42, 43, 44, 54, 55, 61, 62, 64, 70, 71, 72, 81, 83, 84, 87, 89, and 90). RESULTS: The expression of p16INK4A was significantly correlated with HR-HPV infection. Patients infected with HR-HPV had 0.644 times higher possibility to express p16INK4A gene compared to those infected with LR-HPV. LR-HPV genotypes detected in CA patients were HPVs 6, 11, 42, 61, 54, 81, 87, 89, and 90 and HR-HPV genotypes were HPVs 18, 26, 45, 51, 52, 67, 68B, 69, and 82. LR-HPV was found in 19/33 of patients and HR-HPV was in 14/33 of patients. The expression of p16INK4A in CA lesions was diffuse in15.2% of patients, was focal in 24.2% of patients , was sporadic in 39.4% of patients were, and was negative in 21.2% of patients . In LR-HPV group, there was no diffuse expression, focal expression was observed in 15.8%, sporadic in 47.4%, and negative in 36.8%, while in HR-HPV group, p16INK4A expression was detected in all lesions , in a way that its expression was diffuse in 35.7%, focal in 35.7%, and sporadic in 28.6%. CONCLUSION: IHC is a routine method in histopathological diagnosis, therefore the detection of p16INK4A expression by IHC can be used as a biomarker for HR-HPV infection diagnosis.

Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice.

Diabetes mellitus (DM) is one of the major causes of death in the world. There are two types of DM-type 1 DM and type 2 DM. Type 1 DM can only be treated by insulin injection whereas type 2 DM is commonly treated using anti-hyperglycemic agents. Despite its effectiveness in controlling blood glucose level, this therapeutic approach is not able to reduce the decline in the number of functional pancreatic ß cells. MST1 is a strong pro-apoptotic kinase that is expressed in pancreatic ß cells. It induces ß cell death and impairs insulin secretion. Recently, a potent and specific inhibitor for MST1, called XMU-MP-1, was identified and characterized. We hypothesized that treatment with XMU-MP-1 would produce beneficial effects by improving the survival and function of the pancreatic ß cells. We used INS-1 cells and STZ-induced diabetic mice as in vitro and in vivo models to test the effect of XMU-MP-1 treatment. We found that XMU-MP-1 inhibited MST1/2 activity in INS-1 cells. Moreover, treatment with XMU-MP-1 produced a beneficial effect in improving glucose tolerance in the STZ-induced diabetic mouse model. Histological analysis indicated that XMU-MP-1 increased the number of pancreatic ß cells and enhanced Langerhans islet area in the severe diabetic mice. Overall, this study showed that MST1 could become a promising therapeutic target for diabetes mellitus.

GENOTYPING OF HUMAN PAPPILOMAVIRUS IN CERVICAL PRECANCEROUS LESION AND SQUAMOUS CELL CARCINOMA AT DR. SOETOMO HOSPITAL, SURABAYA, INDONESIA.

BACKGROUND: Cervical cancer caused by human papilloma virus (HPV), is the second most common cancer for women. This cancer is distributed worldwide, with ~80% of cases are found in the developing countries. In Indonesia, data of HPV genotypes are still limited and do not represent all regions of the country. Thus, here we report genotyping of HPV samples collected from the Dr. Soetomo Hospital Surabaya Indonesia patients, in 2013. MATERIALS AND METHOD: A cross sectional study was performed using 68 paraffin blocks of low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC) cervix. RESULT: This study showed that HPV genotypes found in LSIL samples are HPV 16, 18, 6/33 or 68/72. Furthermore, those in HSIL are HPV 16, 18, 52, 59, 67, 6/18, 6/45, 16/67, 26/61, or 52/67, while in SCC are HPV 16, 18, 45, 52, 56, 16/18 or 16/45. Single-genotype infection, i.e. by HPV 16, 18, 45, 52, 56, 59, or 67, was observed in 86.77% (59/68) of samples, whereas multiple-genotype infections, i.e. by HPV 6/18, 6/33, 6/45, 16/18, 16/45, 16/67, 26/61, 52/67, or 68/72, was found in 13.23% (9/68) of the samples. CONCLUTIONS: The mostly HPV genotype identified in this study is HPV 16 (62.68%), then followed by HPV 18 (20.9%), HPV 45 (5.97%), 52 (5.97%), and 67 (4.48%). HPV 16 and 18 have used as vaccine, and HPV 45 has cross reaction with HPV 18, then HPV 52 and 67 should be considered as the second-generation HPV vaccines.