Interobserver Agreement in Vascular Invasion Scoring and the Added Value of Immunohistochemistry for Vascular Markers to Predict Disease Relapse in Stage I Testicular Nonseminomas

Abstract

Vascular invasion has been identified as an informative risk factor for relapse in stage I testicular nonseminomas, used to tailor treatment. We investigated interobserver agreement in vascular invasion reporting and studied the potential additional value of immunohistochemistry for vascular markers for predicting relapse. Patients (n = 52) with stage I testicular nonseminomas undergoing surveillance (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006) were included (median follow-up of 66 mo). Two formalin-fixed paraffinembedded blocks with > 1 cm 2 tissue and tumor/normal parenchyma interface were stained with hematoxylin and eosin and CD31, FVIII, and D2-40. Slides were assessed by 3 independent testicular germ cell tumor-dedicated pathologists, and agreement was assessed using Cohen κ statistic. Sensitivity, specificity, and accuracy of vascular invasion scoring in predicting relapse were calculated. Agreement among testicular germ cell tumordedicated pathologists was moderate (κ = 0.49 to 0.54), as was performance in predicting disease relapse (particularly, specificity of 86%). Immunohistochemistry increased overall sensitivity (71%), but decreased specificity (71%) in predicting relapse. All patients (n = 8) with both blood and lymphatic vascular invasion developed a relapse. In multivariable analysis (including age, tumor size, rete testis invasion, and serum tumor markers), only vascular invasion had an independent impact in predicting relapse. Assessment of vascular invasion by testicular germ cell tumor-dedicated pathologists is good and is clinically meaningful, predicting disease relapse. Immunohistochemistry for vascular markers improves sensitivity of detecting disease relapse and allows for the identification of high-risk patients with both blood and lymphatic vascular invasion simultaneously, potentially of interest for tailored chemotherapy.

Prediction of relapse in stage I testicular germ cell tumor patients on surveillance: investigation of biomarkers

“…Vascular invasion is the most discriminative biomarker so far, even in multivariable analyses [12,13]. Recently, we confirmed the value of vascular invasion assessment in a surveillance cohort of stage I non-seminoma patients [16]. Moreover, we demonstrated that all patients depicting simultaneously lymph vessel and blood vessel invasion developed relapse; possibly, if validated, this should further identify high-risk patients.…”

“…One of the limitations of our work is its retrospective nature and the relative small cohort size. However, the power is the true surveillance cohort of 70 stage I patients (partly already described in [16]), avoiding confounding factors related to any treatment except initial orchiectomy. Also, and because our cases derive from several institutions across the Netherlands, our findings do not reflect a selection bias due to inclusion of patients from a single center.…”

Utility of Serum miR-371a-3p in Predicting Relapse on Surveillance in Patients with Clinical Stage I Testicular Germ Cell Cancer

“…In seminomas, only the size of the primary tumor has been validated, although this is not clinically useful as the difference between high-and low-risk relapse estimates range from 5-10% to 20-25% [5,6]. For NSGCTs, the presence of lymphovascular invasion (LVI) and, to a lesser extent, the predominance of embryonal carcinoma are associated with relapse [7][8][9][10]. The presence of LVI confers a 50% chance of relapse compared with 15% in those without, while pooled relapse rates were 40% for patients with embryonal carcinoma predominance.…”

Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm

“…The latter comprise a complex array of subtypes that include embryonal carcinoma (EC), choriocarcinoma (CH), yolk sac tumor (YST), and teratoma (TE) [1][2][3][4][5][6][7]. Overall, TGCTs represent a model of curable disease, with most patients presenting with stage I disease (around 70%), but approximately 75% of these are cured with orchiectomy alone, without the need for subsequent adjuvant treatments [4,8,9]. For those who require systemic therapy, TGCTs present extreme sensitivity to cisplatin-based chemotherapy, due to their unique molecular background [3,10].…”