Cancer stem cells are involved in radioresistant cancers. Transcription factors Sry-related HMG box (SOX2) and octamer binding transcription factor 4 (OCT4) can confer pluripotent cell characteristics and self-renewal ability and are involved in carcinogenesis, metastasis, tumor recurrence, and resistance to therapy. Apoptosis, DNA repair, and telomerase factors also contribute to radioresistance. We sought to identify the role of SOX2 and OCT4 as cancer stem cell markers and their effects on apoptosis (via caspase 3), DNA repair (Chk1) and telomerase (hTERT) in conferring resistance to radiotherapy. We conducted a case-control study of 40 patients with stage IIIB cervical squamous cell carcinoma who completed radiation therapy at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients were classified according to their treatment response as having exhibited a complete or incomplete response. Clinical follow-up and Pap smears were performed between six and 12 months after therapy for those with a good initial response to determine the final response to therapy. Immunohistochemistry was used to analyze SOX2, OCT4, caspase-3, Chk1, and hTERT expression in paraffin sections of the initial biopsy. Strong expression of SOX2 (p = 0.011, p = 0.001) and OCT4 (p < 0.001, p < 0.001) was significantly associated with both an incomplete initial and final therapy response, respectively. Multivariate analysis showed that SOX2 and OCT4 expression levels were the strongest markers of an incomplete response to radiotherapy (odds ratio (OR) = 5.12, p = 0.034, and OR = 17.03, p = 0.004, respectively). Strong expression of SOX2 and OCT4 may be a good indicator of incomplete radiotherapy outcome in patients with stage IIIB cervical cancer.

Radioresistance poses a significant challenge in the effective treatment of cervical cancer, often leading to poor patient outcomes. MicroRNA-21 (miR-21) and MicroRNA-145 (miR-145) are oncogenic micro-RNAs associated with various cancers, including cervical cancer, but their potential as predictive biomarkers for radioresistance remains underexplored. This study aimed to investigate the association between miR-21 and miR-145 expressions and the response to radiation therapy in cervical cancer patients. An analytical cross-sectional study was conducted on 140 subjects with cervical cancer stages IIIB and IVA who received definitive radiotherapy. miR-21 and miR-145 expressions were measured using real-time reverse transcriptase–polymerase chain reaction (RT-qPCR). A total of 102 subjects (72.9%) were classified as having stage III cervical cancer, and 38 subjects (27.1%) were classified as having stage IV cervical cancer. Disease progression occurred in 60.7% of subjects. The cut-off value for miR-21 expression was 0.00088 nmol/(mg/mL) (AUC 0.676, sensitivity 70.8%, specificity 50.8%), and a higher expression was significantly associated with radioresistance (p = 0.010). miR-145, with a cut-off of 0.0239 nmol/(mg/mL) (AUC 0.612, sensitivity 67.5%, specificity 45.5%), showed no significant association with treatment response (p = 0.132). Combining miR-21 and miR-145 (AUC 0.639, sensitivity 68.6%, specificity 46.9%, p = 0.063) did not significantly improve the predictive accuracy. This study suggests that an elevated miR-21 expression is significantly associated with radioresistance in cervical cancer patients, while miR-145 expression shows no significant correlation with treatment response. Additionally, combining miR-21 and miR-145 does not enhance the predictive power.

Background: This study aims to describe the factors associated with dysplastic changes in sinonasal inverted papilloma (SIP) including somatic EGFR mutation, FoxM1 expression, HPV status, and their association with dysplastic changes. Methods: A cross-sectional, analytical study was conducted comprising 34 samples of histologically-confirmed diagnosis of SIP. The samples were further grouped into 2 groups: 20 samples without associated dysplastic changes, and 14 samples with associated dysplastic changes. The numbers of FoxM1 positively-expressed cells, EGFR mutation, and HPV status were compared among two groups using appropriate comparative statistics. Results: There was statistically-significant difference of FoxM1 expression between SIP and SIP with dysplasia (10% vs 100%; p<0.001). EGFR mutation was identified in 6 samples (30.0%) of the SIP and 5 samples (35.7%) of SIP with dysplasia. No difference of EGFR mutant proportion among two groups. HPV DNA was detected in 5 samples (25.0%) of SIP versus 9 samples (64.3%) of SIP with dysplasia. There was significant difference of HPV status among two groups (p=0.022). The high-risk subtypes were found in most HPV positive samples (57.1%), while low-risk subtypes and out panel subtypes were found 14.3% and 21.4%, respectively. Conclusions: FoxM1 was overexpressed in SIP with malignant transformation. FoxM1 along with HPV status is associated with dysplastic changes in the SIP. FoxM1 immunostaining is potential to be a biomarker of malignant transformation in SIP.

Background & Objective: The expression of matrix metalloproteinase-9 (MMP-9) and chemokine receptor 7 (CCR7) is significantly associated with tumor invasion and metastasis. Little is known regarding the potential of these markers in predicting cancer metastasis in Laryngeal Squamous Cell Carcinoma (LSCC). Therefore, this study aimed to dissect the potential of these markers in predicting the lymph node metastasis in LSCC patients.Methods: Sixty tissue samples were obtained from the patients diagnosed pathologically with LSCC who underwent partial or total laryngectomy. The expression of MMP-9 and CCR7 was measured using the immunohistochemistry staining in the tissue samples of LSCC patients. The ROC (receiver operating characteristic) curve was used to determine the most significant cut-off points of expression according to the highest sensitivity and specificity of both the markers to predict the lymph node metastasis in LSCC. Then, the relationship between the clinicopathology features and the expression of MMP-9 and CCR7 was evaluated.Results: The expression of both MMP-9 and CCR7 was significantly correlated with the lymph node metastasis in LSCC (P 4 cm) had significantly higher expression of MMP-9 and CCR7 (P<0.002 and P<0.001, respectively). The Elevated expression level of CCR7 statistically correlated with higher MMP-9 expression (P<0.001).Conclusion: MMP-9 and CCR7 might be beneficial as predictors of lymph node metastasis in LSCC patients.

Background: Nasopharyngeal cancer is commonly associated with Epstein–Barr virus (EBV) infection, especially undifferentiated non-keratinized histology. EBV DNA quantification through nasopharyngeal brushing was previously reported to be not related to disease stage. This study aimed to reinvestigate the relationship of EBV viral load in tumor tissue with tumor extensiveness by more accurate EBV DNA quantification through microscopically confirmed tumor cells from nasopharyngeal biopsy. Method: The specimens for EBV DNA quantification were derived from histopathology slides which were pre-treated following the QIAsymphony^® SP protocol for tissue DNA extraction. Then, the extracted DNA underwent real-time polymerase chain reaction (RT-PCR) using the artus^® EBV RG PCR Kit for EBV DNA quantification. The tumor volume was determined by delineating the gross tumor based on 3D imaging of the patient’s nasopharynx. Result: Twenty-four subjects were included in this study. All subjects were stage III and above, with more males (75%) than females. EBV viral load in tumor cells was found to have no correlation to tumor volume both in local and nodal regions. The median local tumor volume was 81.3 cm³ ± 80 cm³. The median EBV viral load in tumor cells was 95,644.8 ± 224,758.4 copies/100 ng of DNA. The median nodal or regional tumor volume was 35.7 ± 73.63 cm³. Conclusion: EBV viral load from tumor cells from nasopharyngeal biopsy has no relationship with tumor extensiveness in nasopharyngeal cancer. The presence and amount of EBV in tumor cells did not translate into larger or smaller tumors. The EBV viral proteins and RNAs were perhaps more likely to confer some prognostic information due to the fact that those molecules were related to carcinogenesis.

Objective: To investigate the relationship between Yes-Associated Protein (YAP) and Vascular Endothelial Growth Factor-A (VEGF-A) in nasopharyngeal carcinoma (NPC) and evaluate their potential as predictive biomarkers for distant metastasis. Methods: This observational analytic study was conducted from May to August 2023, including 60 NPC cases diagnosed histopathologically at the Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital. The study involved 30 NPC cases with distant metastasis and 30 without distant metastasis. Immunohistochemical analysis was performed using primary antibodies (rabbit YAP, D8H1X; mouse VEGF, clone C-1 sc-7269). Expression levels of YAP and VEGF-A were semi-quantitatively assessed using the H-score formula on 500 tumor cells. Cutoff points for YAP and VEGF-A were determined through Receiver Operating Characteristic (ROC) curve analysis and the Youden index. Statistical analyses, including Chi-square tests, were conducted using SPSS 25.0 to evaluate the relationship between marker expression and the presence of distant metastasis. Results: A significant difference in YAP expression was observed between NPC cases with distant metastasis (80%) and those without (23.3%, p<0.001). Similarly, VEGF-A expression was notably higher in cases with distant metastasis (86.7%) compared to those without (20%, p<0.001). A significant association between YAP and VEGF-A expression was found (p=0.001). ROC curve analysis showed that YAP (AUC=0.738, 95% CI 0.602-0.874) and VEGF-A (AUC=0.842, 95% CI 0.735-0.950) effectively predict distant metastasis. The double co-high-expression group (elevated YAP and VEGF-A) exhibited a significantly higher rate of distant metastasis compared to the non-double co-high-expression group (p<0.001). Conclusion: Elevated expressions of YAP and VEGF-A are significantly associated with distant metastasis in NPC, suggesting their potential as biomarkers for predicting metastatic risk.