ABSTRACT
Tumors of the head and neck, more specifically the squamous cell carcinoma, often show upregulation of the Hedgehog signaling pathway. However, almost nothing is known about its role in the sinonasal adenocarcinoma, either in intestinal or non-intestinal subtypes. In this work, we have analyzed immunohistochemical staining of six Hedgehog pathway proteins, sonic Hedgehog (SHH), Indian Hedgehog (IHH), Patched1 (PTCH1), Gli family zinc finger 1 (GLI1), Gli family zinc finger 2 (GLI2), and Gli family zinc finger 3 (GLI3), on 21 samples of sinonasal adenocarcinoma and compared them with six colon adenocarcinoma and three salivary gland tumors, as well as with matching healthy tissue, where available. We have detected GLI2 and PTCH1 in the majority of samples and also GLI1 in a subset of samples, while GLI3 and the ligands SHH and IHH were generally not detected. PTCH1 pattern of staining shows an interesting pattern, where healthy samples are mostly positive in the stromal compartment, while the signal shifts to the tumor compartment in tumors. This, taken together with a stronger signal of GLI2 in tumors compared to non-tumor tissues, suggests that the Hedgehog pathway is indeed activated in sinonasal adenocarcinoma. As Hedgehog pathway inhibitors are being tested in combination with other therapies for head and neck squamous cell carcinoma, this could provide a therapeutic option for patients with sinonasal adenocarcinoma as well.
Subject(s)
Adenocarcinoma , Hedgehog Proteins , Immunohistochemistry , Signal Transduction , Zinc Finger Protein Gli2 , Humans , Hedgehog Proteins/metabolism , Hedgehog Proteins/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Male , Female , Zinc Finger Protein Gli2/metabolism , Zinc Finger Protein Gli2/genetics , Middle Aged , Pilot Projects , Aged , Patched-1 Receptor/metabolism , Patched-1 Receptor/genetics , Zinc Finger Protein GLI1/metabolism , Zinc Finger Protein GLI1/genetics , Zinc Finger Protein Gli3/metabolism , Zinc Finger Protein Gli3/genetics , Paranasal Sinus Neoplasms/metabolism , Paranasal Sinus Neoplasms/pathology , Adult , Gene Expression Regulation, Neoplastic , Nerve Tissue Proteins , Nuclear ProteinsABSTRACT
Background and Objectives: The aim of this retrospective study was to determine the difference in VEGF-A expression in adenocarcinoma and squamous cell cervical cancer and to show the influence of VEGF-A expression on clinical, pathological, and therapeutic prognostic factors on the outcome of treatment and the survival of patients. Materials and Methods: The study included patients with cervical cancer who were treated in the period from 1 January 2010 to 31 December 2021 at the Clinic for Gynecology and Obstetrics, University Hospital Centre, Osijek. The researchers conducted a retrospective analysis of data from patients' medical history, along with the pathohistological findings and oncologist findings. The study included 66 patients with cervical cancer (divided into two subgroups of 33 with adenocarcinoma or squamous cell cervical cancer). Diagnosis was based on the pathohistological status and FIGO staging. VEGF-A expression was significantly higher in adenocarcinoma. Subjects with a higher expression of VEGF-A had a significantly higher rate of disease progression and a higher possibility for lethal outcome. Results: Statistically significant prognostic factors in bivariate analysis in predicting a negative treatment outcome were: older age, greater depth of stromal invasion, FIGO IIB stage, chemotherapy, and positive lymph nodes. In the multivariate analysis, age and positive lymph nodes were shown to be significant predictors for a negative treatment outcome. Conclusions: VEGF-A has shown to be statistically more expressed in adenocarcinoma, which correlates with disease progression, but not statistically significant in multivariate regression analysis as an independent prognostic factor for poor survival of the subjects.
Subject(s)
Adenocarcinoma , Breast Neoplasms , Carcinoma, Squamous Cell , Uterine Cervical Neoplasms , Female , Humans , Adenocarcinoma/pathology , Breast Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Disease Progression , Epithelial Cells/pathology , Neoplasm Staging , Prognosis , Retrospective Studies , Uterine Cervical Neoplasms/pathology , Vascular Endothelial Growth Factor AABSTRACT
Folate receptor alpha (FRα) is a membrane-bound protein with a high affinity for folate, which is necessary for the biosynthesis of amino acids and nucleotide bases. It has been shown to be a potential prognostic and therapeutic target, primarily in lung and ovarian cancer, as well as in breast cancer. The aim of this study was to examine FRα expression in a cohort of patients with triple negative breast cancer (TNBC), in correlation with clinicopathological parameters and prognostic factors. By using polyclonal FRα antibody on archival paraffin blocks immunohistochemistry was performed. To evaluate the expression of FRα, H-score was used, which marks both the proportion of stained cells and the intensity of staining. Statistical analysis correlating FRα expression with clinicopathologic parameters and clinical outcome were performed. FRα was expressed in most of the patients (85%). Significant correlation of expression and histologic grade (Mann Whitney U test, P = 0,03) and type of tumor (P = 0,02), was found. It was noticed that with higher Ki-67 proliferation index values, H-score has lower values (r = -0,284, P = 0,006). Multivariant regression analysis (Cox regression, Stepwise method) showed H-score as a significant predictor for the risk of disease recurrence (OR = 1,005, P = 0,04). No correlation between FRα expression and overall survival (OS) and disease-free survival (DFS) was found. In conclusion, FRα is highly expressed in TNBC, and, given the correlation with clinicopathological parameters, subpopulation of patients could be identified that could be potential targets for new therapeutic perspectives in the treatment of this breast cancer subtype.
