Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis

Abstract

BACKGROUND The purpose of this study was to develop a reliable model to identify clinical Stage I nonseminomatous germ cell tumors (NSGCTs) associated with low risk or high risk for occult retroperitoneal metastasis, so that the model could be used to customize the therapeutic approach for patients with these tumors. The model was to be based on pathohistologic parameters and immunohistochemical expression of proliferation markers, proteases, and adhesion molecules in the primary tumor. METHODS One hundred forty‐nine patients with clinical Stage I NSGCTs underwent retroperitoneal lymphadenectomy and were included in the study. Three to five paraffin embedded, formalin fixed tissue blocks were available from each patient and were analyzed for the following histopathologic features associated with pathologic Stage I or II disease: the presence or absence of vascular invasion (VI), the presence or absence of tunic invasion, and the percentage of each histologic type present in the primary tumor. Immunohistochemical expression of MIB‐1, p53, bcl‐2, cathepsin D, and E‐cadherin was evaluated using a semiquantitative scoring system. Statistical analysis was performed with univariate and multivariate logistic regression models. RESULTS The percentage of embryonal carcinoma (%EC, P < 0.001) and the presence of VI (P < 0.0001) and tunic invasion (P < 0.002) were the most significant independent risk factors associated with pathologic Stage II disease. A combination of %EC and VI allowed correct prediction of final pathologic stage for 88% of clinical Stage I patients. Cutoff values including both variables identified the correct pathologic stage for 131 of 149 patients (88%). Less than 45% EC and the absence of VI correctly identified pathologic Stage I disease in 91.5% of patients; more than 80% EC and the presence of VI correctly predicted pathologic Stage II in 88%. In univariate analysis, only p53 (P < 0.03) and E‐cadherin (P < 0.001) expression were significantly different in the embryonal carcinoma component of pathologic Stage I and II NSGCT. To evaluate prospectively the clinical utility of the new derived cutoff points, the data were applied to 10 consecutive patients with clinical Stage I NSGCT who underwent retroperitoneal lymphadenectomy; pathologic Stage I and II were correctly predicted for 5 of 6 Stage I and 4 of 4 Stage II patients, respectively. CONCLUSIONS %EC and the presence or absence of VI appear to be reliable prognosticators to identify patients at high risk and low risk for occult retroperitoneal disease. In cases of clinical Stage I NSGCT, p53, bcl‐2, MIB‐1, cathepsin D, and E‐cadherin did not appear to be of prognostic significance. The authors recommend that all patients with clinical Stage I NSGCT have their primary orchiectomy specimens evaluated for %EC and the presence of VI to determine their risk for occult retroperitoneal metastasis. Cancer 1998;83:1002‐1011. © 1998 American Cancer Society.

Involvement of dysadherin and E-cadherin in the development of testicular tumours

“…Heidenreich et al (1998) reported E-cadherin expression in 76.1% of NSGCTs, as well as positive staining in benign testicular tissue. The latter is not confirmed by our study, neither by that of Saito et al (2000), who showed that E-cadherin was not expressed in normal germ cells.…”

“…Since the frequency of testicular neoplasms, which affect primarily young males, has increased in developed countries the search for new molecules possibly involved in their pathogenesis and progression is of high importance (Heidenreich et al, 1998;Delgado et al, 2000;Aubry et al, 2001). Embryonal carcinoma is composed of primitive carcinoma-like cells with minimal or no signs of differentiation.…”

“…The material consisted of 37 seminomas (26 classic, five spermatocytic, and six anaplastic), 45 embryonal carcinomas, 10 mixed germ cell tumours, two yolk sac tumours, 10 mature, and eight immature teratomas and eight non-Hodgkin B-cell lymphomas. They corresponded to an equal number of patients (mean age 32.9 years, range 17 -78) with clinical stage I testicular neoplasms, as defined by negative radiographic findings of chest, abdomen, and pelvis as well as decrease of the relevant tumour markers after radical orchiectomy (Heidenreich et al, 1998). In seven seminomas and nine embryonal carcinomas preinvasive CIS/ITGCNU was noted at the periphery of the invasive tumour.…”

“…Lymphatic invasion was recognised when tumour cells either adhered to a vessel wall of usually irregular shape or filled a space lined by endothelial cells without red blood cells, while venous invasion was noted when the vessel wall was thicker and the space contained red blood cells. For statistical purposes both lymphatic and venous invasion were recorded as vascular invasion (VI), as previously reported (Heidenreich et al, 1998).…”

“…Abnormal E-cadherin expression (heterogeneous, cytoplasmic, or absent) has been detected immunohistochemically in a variety of poorly differentiated, invasive and metastatic carcinomas, such as gastric adenocarcinoma, lobular breast carcinoma, colorectal tumours, prostate adenocarcinoma, pancreatic, and bladder cancer (Charalabopoulos et al, 2002(Charalabopoulos et al, , 2004Chang et al, 2002;Hirohashi and Kanai, 2003;Zhang et al, 2004;Massarelli et al, 2005). Regarding testicular neoplasms, there are less than a handful of studies, with conflicting results (Heidenreich et al, 1998;Saito et al, 2000;Honecker et al, 2004).…”