| Title: |
Intranuclear Peripheral Overexpression of Pituitary-Tumor-Transforming Gene 1: Immunohistochemical Biomarker of Lymph Node Involvement in Testicular Seminoma. |
| Authors: |
Vergani, Edoardo; Pierconti, Francesco; Pozza, Carlotta; Merenda, Elisabetta; Girardi, Paola; Tenuta, Marta; Benvenuto, Roberta; Teveroni, Emanuela; Gulino, Gaetano; Franco, Giorgio; Magliocca, Fabio Massimo; Rocco, Bernardo; Isidori, Andrea; Pontecorvi, Alfredo; Milardi, Domenico |
| Source: |
Cancers; Apr2026, Vol. 18 Issue 7, p1163, 16p |
| Subject Terms: |
LYMPH nodes; RISK assessment; PEARSON correlation (Statistics); CANCER invasiveness; CANCER relapse; ADIPOSE tissues; SEMINOMA; T-test (Statistics); RECEIVER operating characteristic curves; DATA analysis; PREDICTION models; SCIENTIFIC observation; LOGISTIC regression analysis; NECROSIS; COMPUTED tomography; TUMOR markers; RETROSPECTIVE studies; DESCRIPTIVE statistics; CHI-squared test; CANCER patients; MAGNETIC resonance imaging; GENE expression; IMMUNOHISTOCHEMISTRY; METASTASIS; ONCOGENES; STATISTICS; STAINS & staining (Microscopy); DATA analysis software; COMPARATIVE studies; CONFIDENCE intervals; INDIVIDUALIZED medicine; SENSITIVITY & specificity (Statistics); DISEASE risk factors |
| Geographic Terms: |
ITALY |
| Abstract: |
Simple Summary: Testicular seminoma is the most common cancer in young adult men and generally has an excellent prognosis. However, a subset of patients develops lymph node metastases and may require more intensive treatment. Clinicians rely on histological features to estimate the risk of disease spread, but these factors are not always reliable. Pituitary-Tumor-Transforming Gene 1 (PTTG1) is a protein involved in cell division and has been linked to tumor aggressiveness. In this study, we evaluated whether the expression of PTTG1 in tumor tissue could be associated with lymph node involvement in seminoma. We analyzed tumor samples from 51 patients using immunohistochemistry and developed a scoring system based on intranuclear PTTG1 expression. Higher PTTG1 scores were associated with the presence of lymph node metastases at diagnosis, independently of tumor size. These results suggest that PTTG1 immunohistochemical is associated with lymph node metastasis but this finding requires prospective validation in larger cohorts. Background/Objectives: Testicular germ cell tumors, particularly seminoma, represent the leading cause of cancer in men aged 15–40 years. The decision about adjuvant therapy relies on histological features with uncertain prognostic value. The Pituitary-Tumor-Transforming Gene 1 (PTTG1), which encodes the securin protein, is crucial in sister chromatid separation. Our previous in vitro studies demonstrated that PTTG1 nuclear expression promotes invasiveness, dedifferentiation, and neolymphangiogenesis in testicular seminoma. Methods: We conducted a hypothesis-generating retrospective observational study on 51 patients (aged 23–68) with testicular seminoma, with (43%) or without (57%) lymph node involvement, evaluating potential correlations between PTTG1 and currently known prognostic factors. Clinical and pathological data were collected, including lymph node involvement, recurrence, necrosis, rete testis invasion, vascular invasion, and adipose tissue invasion. An immunohistochemical scoring system assessing intranuclear PTTG1 expression was developed. Results: The PTTG1 score was related to lymph node metastasis and adipose tissue invasion. ROC curve analysis showed that the PTTG1 immunohistochemical score showed good discriminatory ability in identifying lymph node involvement (AUC = 0.939); the optimal cut-off was 4.0 (sensitivity 90.5%; specificity 57.1%), while the ROC curve for adipose tissue invasion was inadequate. Lymph node metastasis also correlated with necrosis; however, logistic regression confirmed that PTTG1 score was independently associated with nodal involvement (p = 0.002), regardless of tumor size and necrosis. Conclusions: Our findings suggest a correlation between PTTG1 expression and lymphadenopathy at diagnosis, independent of tumor size and T stage. It may reflect biological features associated with lymphatic dissemination and requires further investigation in larger prospective studies. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |