Topoisomerase 2α plays a pivotal role in the tumor biology of stage IV thymic neoplasia

Abstract

BACKGROUND.Microsatellite studies in histologic types B3 and C thymic neoplasia detected gains on chromosome 17q, which contains the Her‐2/neu and its juxtaposed topoisomerase 2α (T2α) genes. The study aimed to evaluate their impact on tumor biology and survival of advanced thymic neoplasia patients.METHODS.From 1991 to 2005, 36 consecutive stage IV thymic carcinoma patients were treated, 18 men and 18 women, aged 11 to 84 years. There were 22 thymic carcinoma, 13 type B3, and 1 type B2 thymoma. Patients received treatment consisting of surgical resection, combination chemotherapy with the CAP (cyclophosphamide, Adriamycin, cisplatin) regimen, or radiation therapy potentiated by high‐dose weekly 5‐fluorouracil infusion. Permutations of these 3 treatment modalities were prescribed as necessary.RESULTS.T2α gene amplification was detected in 4 of 14 thymic carcinoma and 1 of 15 type B3 thymoma. Three thymic carcinoma patients had Her‐2/neu coamplification and these 3 patients had rapidly growing tumor and extensive disease at initial diagnosis. CAP was prescribed in 28 patients and 20 patients responded (response rate, 71.4%, 95% confidence interval [CI]: 52.8% to 85%); all responders overexpressed (≥10% nuclei positive) the T2α protein, whereas 4 nonresponders had very low expression. T2α overexpression predicts CAP response, and its absence predicts resistance (P = .001). Overall survival was significantly prolonged if the tumor was resectable (P = .001), of type B3 histology (P = .0039), and had no Her‐2 gene amplification (P = .0081).CONCLUSION.T2α and Her‐2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients. Cancer 2007;109:502–509. © 2006 American Cancer Society.

Prognostic effect of class III β-tubulin and Topoisomerase-II in patients with advanced thymic carcinoma who received combination chemotherapy, including taxanes or topoisomerase-II inhibitors

“…In contrast, the data of the present study did not confirm the significance of topo-II overexpression in predicting responses to chemotherapy. This discrepancy may be attributed to the fact that, contrary to the study by Liu et al (44), the present study was restricted to patients with ATC and included various chemotherapy regimens. In agreement with the data of the present study, no obvious association between topo-II expression and response to chemotherapy was detected in lung cancer (24–26,45).…”

“…In addition, Liu et al (44) have demonstrated that topo-II overexpression was significantly correlated with chemosensitivity in 20 patients with TET receiving anthracycline-based chemotherapy. In contrast, the data of the present study did not confirm the significance of topo-II overexpression in predicting responses to chemotherapy.…”

The Multidisciplinary Approach to Thymoma: Combining Molecular and Clinical Approaches

“…Topoisomerase 2-alpha protein overexpression, detected in four of 14 cases of thymic carcinoma and of one of 15 type B3 thymoma, was reported to predict response to cyclophosphamide, adriamycin, cisplatin (CAP) chemotherapy (cyclophosphamide, adriamycin, cisplatin), whereas HER2/neu or topoisomerase 2-alpha gene amplification and expression of ERCC1 or thymidylate synthase did not. 17 Thymoma tumor specimens compared with normal thymus tissue have higher mRNA levels of thymidylate synthase (which correlates with resistance to 5-fluorouracil) and elevated dihydropyrimidine dehydrogenase (which degrades 5-flurouracil), but this did not correlate with clinicopathologic factors. 18…”

Salvage Chemotherapy in Patients with Previously Treated Thymic Carcinoma

“…Table 1 shows a summary of platinum-based chemotherapy as first-line treatment in patients with advanced TC. Previous studies have identified that cisplatinadriamycin-cyclophosphamide (CAP), cisplatin-doxorubicin-cyclophoshamide-vincristine (ADOC), cisplatin-etoposide (VP16), cisplatin-docetaxel, and carboplatin-paclitaxel are the most common regimens administered in patients with TC [2,[4][5][6][7][8][9][10][11][12][13][14][15]. The overall response rate (ORR) of platinum-based chemotherapy was yielded approximately 30-40% (from 21% to 70%), regardless of the small sample size.…”

“…The overall response rate (ORR) of platinum-based chemotherapy was yielded approximately 30-40% (from 21% to 70%), regardless of the small sample size. Although high-intensity regimens, such as CAP or ADOC, increase the response rate, severe adverse events were also observed, although CAP is a standard regimen at least in Europe for thymoma [4][5][6][7][8][9][10]. Meanwhile, cisplatin plus etoposide or carboplatin plus paclitaxel are commonly administered to patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), known as active and tolerable regimens.…”