Background and Objectives Testicular Germ-cell Tumour (TGCT) is the most frequent tumour in the young male and its occurrence is increasing in Europe. Prognosis is favourable, and TGCT basically represents a model of curability of solid tumours. However, clinical management and follow-up of both localized and locally advanced TGTCs is still complex and the risk of treatment delay or, conversely, of overtreatment is high. According to this assumption we focused on two different TGCTs patients categories to test a new biomarker that may allow to improve TGCTs management. 371a-p microRNA showed the ability to identify vital cancer in GCTs and its performance in term of sensitivity and specificity exceed the available markers. We tested its diagnostic accuracy in small testicular masses and in low volume retroperitoneal disease (Stage IIA or IIB). In the first setting we know that up to 70% of small testicular lesions (<20 mm) are benign. Conversely, in the second setting we know that from 9 to 20% of patients who have retroperitoneal lymphnode dissection RPLND for stage IIA or IIB TGCTs have no nodal disease at definitive pathology. Given this data, new diagnostic biomarkers that may allow to discriminate between the presence or not of TGCTs is needed. Material and Methods We selected patients with small testicular masses between 5 and 20 mm or with low volume retroperitoneal disease. Analysis of 371a-p miRNA in serum will be performed by dedicated biologists. In case of small testicular masses 371a-p miRNA was tested before surgery. Conversely, in low volume retroperitoneal disease it was tested before surgery and at 30 days after surgery. Results 371a-p miRNA was tested in all patients with small testicular masses before surgery. The proposed cut-off for presence of GCTs is 15 as Relative Quantity (RQ). In SGCTs the RQ ranged from 17 to 1857. Of note the patients with the highest value was pT2. In mixed GCT the RQ was 17. Finally, considering all GCTs, the patient with mixed germ cell tumors with burn-out component had an RQ of 8. Conversely, the expression of 371a-p miRNA in patients with no GCT was 5 and 9 (RQ) in Leydig cell tumors, 1 in burn-out tumor, 2 in leiomyoma and 16 in capillary hemangioma. The overall sensitivity is 88% and the overall specificity is 75%. 371a-p miRNA was tested in all small retroperitoneal disease patients before surgery and in 8 of 9 patients at thirty days. The proposed cut-off from the producer (Gold Standard Diagnostics) for presence of GCTs is 15 as RQ. All patients with vital cancer had 371a-p miRNA values over the cut-off. Conversely, 2 on 3 patients with negative specimen for vital cancer had negative 371a-p miRNA values. 371a-p miRNA RQ was higher in patients with larger metastatic depots. Two patients experienced relapse. One patient with elevated tumor markers at 30 days (R.Q. 144.70) who was classified at pathological stage IIB at RPLND. The relapse was retroperitoneal outfield and pulmonary. The other patient was the one with marker elevation after RPLND (Definitive specimen: Burn-out), this patient experienced a 6 months relapse with beta-HCG elevation. Conclusion In patients with small testicular mass and low volume retroperitoneal disease 371a-p miRNA showed a promising role in determining the presence or not of GCTs and in predicting relapse.

CLINICAL VALIDATION OF 371 MICRO-RNA USE IN SMALL TESTICULAR MASSES AND IN STAGE IIA AND IIB<3CM TESTICULAR GERM CELL TUMORS

NAZZANI, SEBASTIANO
2024

Abstract

Background and Objectives Testicular Germ-cell Tumour (TGCT) is the most frequent tumour in the young male and its occurrence is increasing in Europe. Prognosis is favourable, and TGCT basically represents a model of curability of solid tumours. However, clinical management and follow-up of both localized and locally advanced TGTCs is still complex and the risk of treatment delay or, conversely, of overtreatment is high. According to this assumption we focused on two different TGCTs patients categories to test a new biomarker that may allow to improve TGCTs management. 371a-p microRNA showed the ability to identify vital cancer in GCTs and its performance in term of sensitivity and specificity exceed the available markers. We tested its diagnostic accuracy in small testicular masses and in low volume retroperitoneal disease (Stage IIA or IIB). In the first setting we know that up to 70% of small testicular lesions (<20 mm) are benign. Conversely, in the second setting we know that from 9 to 20% of patients who have retroperitoneal lymphnode dissection RPLND for stage IIA or IIB TGCTs have no nodal disease at definitive pathology. Given this data, new diagnostic biomarkers that may allow to discriminate between the presence or not of TGCTs is needed. Material and Methods We selected patients with small testicular masses between 5 and 20 mm or with low volume retroperitoneal disease. Analysis of 371a-p miRNA in serum will be performed by dedicated biologists. In case of small testicular masses 371a-p miRNA was tested before surgery. Conversely, in low volume retroperitoneal disease it was tested before surgery and at 30 days after surgery. Results 371a-p miRNA was tested in all patients with small testicular masses before surgery. The proposed cut-off for presence of GCTs is 15 as Relative Quantity (RQ). In SGCTs the RQ ranged from 17 to 1857. Of note the patients with the highest value was pT2. In mixed GCT the RQ was 17. Finally, considering all GCTs, the patient with mixed germ cell tumors with burn-out component had an RQ of 8. Conversely, the expression of 371a-p miRNA in patients with no GCT was 5 and 9 (RQ) in Leydig cell tumors, 1 in burn-out tumor, 2 in leiomyoma and 16 in capillary hemangioma. The overall sensitivity is 88% and the overall specificity is 75%. 371a-p miRNA was tested in all small retroperitoneal disease patients before surgery and in 8 of 9 patients at thirty days. The proposed cut-off from the producer (Gold Standard Diagnostics) for presence of GCTs is 15 as RQ. All patients with vital cancer had 371a-p miRNA values over the cut-off. Conversely, 2 on 3 patients with negative specimen for vital cancer had negative 371a-p miRNA values. 371a-p miRNA RQ was higher in patients with larger metastatic depots. Two patients experienced relapse. One patient with elevated tumor markers at 30 days (R.Q. 144.70) who was classified at pathological stage IIB at RPLND. The relapse was retroperitoneal outfield and pulmonary. The other patient was the one with marker elevation after RPLND (Definitive specimen: Burn-out), this patient experienced a 6 months relapse with beta-HCG elevation. Conclusion In patients with small testicular mass and low volume retroperitoneal disease 371a-p miRNA showed a promising role in determining the presence or not of GCTs and in predicting relapse.
23-gen-2024
Inglese
MONTANARI, EMANUELE
Università degli Studi di Milano
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/84646
Il codice NBN di questa tesi è URN:NBN:IT:UNIMI-84646