Prognostic value of epidermal growth factor receptor expression in endometrioid endometrial carcinoma

Niikura, Hitoshi; Sasano, Hironobu; Matsunaga, Gen; Watanabe, Keiko; Itō, Kiyoshi; Sato, Shinji; Yajima, Akira

doi:10.1016/0046-8177(95)90013-6

Cited by 44 publications

(31 citation statements)

References 17 publications

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“…Several studies have focused on the expression of erbB-1 and/or erbB-2 and their biological or clinical involvement in endometrial tumorigenesis (27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Expression of erbB-1 and erbB-2 genes in normal and pathological human endometrium

Bryś

Semczuk²,

Rechberger³

et al. 2007

Oncol Rep

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Abstract. Overexpression of the erbB-1 (EGFR, epidermal growth factor receptor) and erbB-2 (HER2/neu) proteins contributes to the aggressive behavior of malignant tumors originating from the endometrium. We currently examined whether the trend of these proteins to overexpression is a direct effect of their gene transcriptional activities. Expression of the erbB-1/erbB-2 genes was measured applying the quantitative RT-PCR technique in 25 uterine carcinomas, 12 normal endometria, a carcinosarcoma and a case of botryoid sarcoma of the uterine cervix. We showed that erbB-1 mRNA was overexpressed in 48% (12/25) and erbB-2 mRNA was overexpressed in 8% (2/25) of the analysed tumors. The level of expression appeared to be significantly higher in the malignant tumors as compared to the benign ones for erbB-1 and for erbB-2 (p=0.0001 and p=0.008, respectively). A significant correlation between erbB-1 overexpression and tumor differentiation was found (Spearman rank correlation test, p<0.001). Concomitant erbB-1 and erbB-2 overexpression was detected only in 1 out of 25 (4%) uterine neoplasms. erbB-1 was overexpressed in a sarcoma botryoides of the uterine cervix. Our data suggest that erbB-1/erbB-2 overexpression is a direct effect of higher than normal transcriptional activity of the encoding genes in a subset of human endometrial carcinomas.

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“…Several studies have focused on the expression of erbB-1 and/or erbB-2 and their biological or clinical involvement in endometrial tumorigenesis (27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Expression of erbB-1 and erbB-2 genes in normal and pathological human endometrium

Bryś

Semczuk²,

Rechberger³

et al. 2007

Oncol Rep

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“…Similar controversies exist regarding the clinical relevance of the epidermal growth factor receptor (EGFR) in EC in general and more specifically in type II EC. EGFR expression has been demonstrated in 43 -67% of patients with endometrial cancer and its association with clinical outcome has been explored with some studies demonstrating an association between EGFR expression and poor clinical outcome (Khalifa et al, 1994;Scambia et al, 1994;Niikura et al, 1995) whereas others show no association (Reinartz et al, 1994). Moreover, the clinical role of EGFR expression specifically in type II EC has not yet been studied.…”

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confidence: 99%

HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer

et al. 2008

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Type II endometrial cancers (uterine serous papillary and clear cell histologies) represent rare but highly aggressive variants of endometrial cancer (EC). HER2 and EGFR may be differentially expressed in type II EC. Here, we evaluate the clinical role of HER2 and EGFR in a large cohort of surgically staged patients with type II (nonendometrioid) EC and compare the findings with those seen in a representative cohort of type I (endometrioid) EC. In this study HER2 gene amplification was studied by fluorescence in situ hybridisation (FISH) and EGFR expression by immunohistochemistry. Tissue microarrays were constructed from 279 patients with EC (145 patients with type I and 134 patients with type II EC). All patients were completely surgically staged and long-term clinical follow up was available for 258 patients. The rate of HER2 gene amplification was significantly higher in type II EC compared with type I EC (17 vs 1%, Po0.001). HER2 gene amplification was detected in 17 and 16% of the cases with uterine serous papillary and clear cell type histology, respectively. In contrast, EGFR expression was significantly lower in type II compared with type I EC (34 vs 46%, P ¼ 0.041). EGFR expression but not HER2 gene amplification was significantly associated with poor overall survival in patients with type II EC, (EGFR, median survival 20 vs 33 months, P ¼ 0.028; HER2, median survival 18 vs 29 months, P ¼ 0.113) and EGFR expression retained prognostic independence when adjusting for histology, stage, grade, and age (EGFR, P ¼ 0.0197; HER2, P ¼ 0.7855). We conclude that assessment of HER2 gene amplification and/or EGFR expression may help to select type II EC patients who could benefit from therapeutic strategies targeting both HER2 and EGFR.

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“…Epidermal growth factor receptor expression has been demonstrated in 43 -67% of patients with endometrial cancer and has similarly been associated with significantly shortened disease-free and overall survival (Khalifa et al, 1994;Scambia et al, 1994;Niikura et al, 1995). Moreover, endometrial cancer demonstrated significantly higher expression levels of the EGFR ligands TGF-a and amphiregulin compared with normal endometrium (Pfeiffer et al, 1997;Ejskjaer et al, 2007).…”

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confidence: 99%

Activity of lapatinib a novel HER2 and EGFR dual kinase inhibitor in human endometrial cancer cells

et al. 2008

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In this study, we explore the therapeutic potential of lapatinib a selective inhibitor of both the EGFR and HER2 tyrosine kinases for the treatment of endometrial cancer. The effect of lapatinib on tumour cell growth and receptor activation was studied in a panel of human endometrial cancer cell lines. Candidate molecular markers predicting sensitivity were assessed by baseline gene expression profiling, ELISA, and western blot analyses. Multiple drug effect/combination index (CI) isobologram analysis was used to study the interactions between chemotherapeutic drugs and lapatinib. Concentration-dependent anti-proliferative effects of lapatinib were seen in all endometrial cancer cell lines tested, but varied significantly between individual cell lines (IC 50 range: 0.052 -10.9 mmol). HER2 overexpression or increased expression of EGFR was significantly associated with in vitro sensitivity (P ¼ 0.024 or 0.011, respectively). Lapatinib exerts growth inhibition in a PTEN-independent manner. Sensitive cell lines also exhibited increased expression of EGFR ligands or HER3. In contrast, lapatinib-resistant cell lines exhibited high androgen receptor (AR) levels or epithelial-to-mesenchymal transition (post-EMT) features. In endometrial cancer cells, at a wide range of clinically achievable drug concentrations, additive and synergistic interactions were observed for lapatinib plus carboplatin, paclitaxel, docetaxel, and doxorubicin. These observations provide a clear biologic rational to test lapatinib as a single agent or in combination with chemotherapy in endometrial cancer with HER2 overexpression. Expression of EGFR, its ligands, HER3, AR, and post-EMT markers warrant further evaluation to help define patients with HER2-nonoverexpressing endometrial cancer most likely to benefit from lapatinib.

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Prognostic value of epidermal growth factor receptor expression in endometrioid endometrial carcinoma

Cited by 44 publications

References 17 publications

Expression of erbB-1 and erbB-2 genes in normal and pathological human endometrium

Expression of erbB-1 and erbB-2 genes in normal and pathological human endometrium

HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer

Activity of lapatinib a novel HER2 and EGFR dual kinase inhibitor in human endometrial cancer cells

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