Histological evidence for the existence of germ cell tumor cells showing embryonal carcinoma morphology but lacking OCT4 expression and cisplatin sensitivity.

The biological basis for manifestation of chemotherapy resistance in metastatic testicular germ cell tumors (GCT) remains obscure and is of particular clinical interest. In nonseminomatous GCT (NSGCT) the pluripotent embryonal carcinoma (EC) cells are the precursors of the manifold differentiated structures but also drive the malignant growth. They are known to be hypersensitive towards DNA-damaging agents and to express the embryonal transcription factor OCT4. We recently characterized EC cells that lack OCT4 expression and show cisplatin resistance. In the present, immunohistochemical study we analyzed the composition of NSGCT with the focus on such OCT4-negative EC cells using a NSGCT xenograft model as well as patient-derived NSGCT samples. In the xenograft model, the cisplatin-sensitive cell line H12.1 gives rise to xenografts where EC structures are mainly composed of OCT4-positive cells, whereas xenografts from the resistant cell line 1411HP exclusively comprise OCT4-negative EC areas. We found that post-chemotherapy residual metastatic tumors of patients can be comprised of exclusively OCT4-negative EC, whereas the matched testicular primary tumor harbors OCT4-positive EC. Thorough histological analyses revealed a few examples of such OCT4-negative EC cells also in the testicular primary tumor as well as in xenografts from the cisplatin-sensitive NSGCT-cell line. For these cells we propose an identity as early extraembryonal progenitor cells directly derived from OCT4-expressing EC cells. This challenges the use of the term EC cell. The data also support our hypothesis that malignant growth of resistant NSGCT may be driven by this cell type.

Postchemotherapy retroperitoneal lymph node dissection in advanced testicular cancer: radical or modified template resection.

BACKGROUND: The anatomical extent of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) has been discussed controversially for many years. OBJECTIVE: To evaluate the necessity of PC-RPLND with modified or radical template resection in patients with advanced nonseminomatous germ-cell tumors (NSGCT) and residual masses following systemic chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: The charts of 152 consecutive patients who were treated at two tertiary referral centers were retrospectively reviewed. INTERVENTION: All patients underwent PC-RPLND, with 54 and 98 patients undergoing a radical template resection and 98 patients undergoing a modified template resection. Modified template resection was performed if the location of the residual mass corresponded to the primary landing zone of testis cancer and the residual mass measured < or = 5 cm in diameter. In all other cases a full bilateral PC-RPLND was chosen. MEASUREMENTS: The following data were analyzed: location of the residual mass, extent of surgery, length of surgery, treatment-associated complications, nerve-sparing approach, adjunctive surgical procedures, postoperative morbidity, duration of hospital stay, early and late complications, relapse rates, cancer-specific survival rates, and overall survival rates. RESULTS AND LIMITATIONS: Overall, 84 patients (55.2%) had necrosis/fibrosis, 45 (29.6%) had mature teratoma, and 23 (15.1%) had vital cancer in the surgical specimens. Antegrade ejaculation was preserved in 85% and 25% of patients undergoing modified and bilateral PC-RPLND (p=0.02), respectively. Eight recurrences (5.2%) were observed after a mean follow-up of 39 mo (range 6-105 mo): one patient had an in-field relapse following modified PC-RPLND, and seven patients had recurrences outside the boundaries of full bilateral PC-RPLNDs. The 2-yr disease-free survival rates were 78.6% and 92.8% for bilateral and modified PC-RPLND, respectively. The limitations of this study were a short follow-up, a limited number of patients, and the retrospective nature of the study. CONCLUSIONS: Full bilateral PC-RPLND is the standard approach to extensive residual masses. In well-defined masses a modified template PC-RPLND does not interfere with oncologic outcome but decreases treatment-associated morbidity.

Gender-specific differences in bladder cancer: a retrospective analysis.

BACKGROUND: A higher incidence of bladder cancer has been reported in men compared with women. Clinical gender differences have been observed but are less well described. OBJECTIVE: This retrospective analysis further examines clinical differences in the development and manifestation of bladder cancer between men and women. METHODS: Consecutive male and female patients with bladder cancer treated between 1969 and 1997 at a single center (University Hospital of Innsbruck, Innsbruck, Austria) were included in the study. Patient characteristics regarding age, tumor classification, localization, and recurrence were compared between male and female patients. Statistical analysis was conducted using the t test, the chi(2) test, and the Kaplan-Meier method, with the log-rank test for subgroup analysis. RESULTS: In the 1,269 patients (876 men, 393 women) who were examined, 1,744 tumors were found. The male-to-female bladder cancer incidence ratio was 2.2:1. Tumors were diagnosed at a significantly younger age in men than in women (mean age: 62 years vs 67 years, respectively; P < 0.001). No difference in the histology of tumors was observed between the sexes. Muscle-invasive tumors more frequently occurred in men than in women (39.8% vs 34.5%; P = NS). In men compared with women, primary tumors were more aggressive (grade 2, 36.6% vs 28.2%; P < 0.001) and tumor recurrences were more invasive (59.0% vs 57.8%; P = NS). Tumors were more often located in the urethra in men than in women (43 [3.4%] vs 9 [1.8%]; P = 0.034), the trigonum (246 [19.8%] vs 75 [14.9%]; P < 0.001), and the bladder dome or vault (128 [10.3%] vs 37 [7.4%]; P = 0.015). Generally, no difference in survival rate was observed between the sexes; only in the subgroup of muscle-invasive tumors (n = 455) did women have a worse overall survival rate than did men (P = 0.022). CONCLUSIONS: Clinical gender differences in bladder cancer appear to have a higher incidence in men than in women. In this analysis, women were older at the age of detection, but had less-invasive and less-aggressive tumors than did men. However, women with muscle-invasive disease had a worse overall survival rate than did men in the same subset.