Shuko Oe

The relationship between ERCC1 expression and clinical outcome in patients with FIGO stage I to stage II uterine cervical adenocarcinoma.

Objective: Several studies have suggested that excision repair cross-complementation group 1 (ERCC1), a protein involved in nucleotide excision repair, is associated with resistance to platinum agent-based chemotherapy or chemoradiotherapy with platinum agents in various types of cancer. Herein we evaluated ERCC1 protein expression in uterine cervical adenocarcinoma and the relationship between this expression, clinicopathological factors, and clinical outcome, particularly in patients receiving adjuvant cisplatin-based chemotherapy or chemoradiotherapy with cisplatin. Methods: Thirty-six patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB to stage IIB cervical adenocarcinoma who underwent radical hysterectomy were evaluated. Excision repair cross-complementation group 1 protein expression was examined by immunohistochemistry in tumor tissues. The relationship between ERCC1 expression levels and clinicopathological factors (age, FIGO stage, histological grade, tumor size, vascular invasion, cervical stromal invasion, and lymph node metastases) and prognosis was evaluated. Results: No significant differences between ERCC1 expression levels and clinicopathological factors were observed. The patients in the ERCC1 high-expression group (n = 7) experienced significantly worse disease-free survival than the patients in the ERCC1 low-expression group (n = 29; P = 0.005). Among the 25 patients who received cisplatin-based chemotherapy or chemoradiotherapy with cisplatin, those with high ERCC1 expression (n = 5) also experienced significantly worse disease-free survival than those with low ERCC1 expression (n = 20; P = 0.002). Moreover, univariate and multivariate analyses revealed that high ERCC1 expression was an independent prognostic factor in patients receiving cisplatin-based chemotherapy or chemoradiotherapy with cisplatin. Conclusions: This is the first analysis of the association between ERCC1 expression and clinical outcomes in patients with uterine cervical adenocarcinoma. High ERCC1 protein expression was revealed to be associated with worse disease-free survival in the patients who received adjuvant cisplatin-based chemotherapy or chemoradiotherapy with cisplatin and was shown to be an independent prognostic factor. Further evaluation with a larger number of patients is required to confirm these preliminary observations.

Expression of podoplanin in epithelial ovarian carcinomas and its potential as a marker for clear cell adenocarcinoma.

Podoplanin is a 43-kd mucin-type transmembrane glycoprotein that is a candidate marker for the pathologic diagnosis of mesothelioma and lymphatic endothelial cells and lymphangiogenesis. The aim of this study was to investigate podoplanin expression in epithelial ovarian carcinomas. Immunohistochemistry was performed on the paraffin-embedded tissues from 78 patients with epithelial ovarian carcinomas consisting of serous adenocarcinoma (SA), endometrioid adenocarcinoma (EM), mucinous adenocarcinoma (MA), and clear cell adenocarcinoma (CCC) cases. Only 36.8% (7/19) of SA, 33.3% (6/18) of EM, and 15.8% (3/19) of MA cases were positive for podoplanin expression, whereas 54.5% (12/22) of CCC samples were positive. Immunohistochemical scores (mean±SD) were 1.2±1.5, 1.9±2.6, 0.8±1.6 and, 3.6±4.0 in SA, EM, MA, and CCC, respectively. Podoplanin expression was significantly stronger in CCC than in other histologic types. However, no significant correlation was observed between its expression and FIGO stage, the presence of endometriosis, lymph node metastasis, or recurrence. There was also no correlation between podoplanin expression and overall survival. We confirmed the expression of podoplanin in epithelial ovarian carcinomas, particularly in CCC. Podoplanin might have utility as a marker for CCC in pathologic diagnosis. Further investigation is needed to clarify the relationship between podoplanin expression and the biologic characteristics of CCC.

Human epidermal growth factor receptor-2 overexpression and amplification in metastatic and recurrent high grade or type 2 endometrial carcinomas

Introduction Human epidermal growth factor receptor (HER)-2 overexpression or gene amplification is more common in high-grade or type 2 endometrial carcinomas. We assessed the discordance of HER-2 expression between primary and metastatic or recurrent endometrial carcinomas. Materials and methods Thirty-six primary, along with 14 metastatic and five recurrent tumors (matched to primaries), pathologically confirmed as high-grade or type 2 endometrial carcinomas, were submitted for immunohistochemistry (IHC) for HER-2. Fluorescence in situ hybridization was performed when the tumors showed HER-2 overexpression (≥2+ IHC score). The results of the IHC and fluorescence in situ hybridization assays were compared between the primary and metastatic or recurrent tumors. The relationships between HER-2 expression and clinicopathological factors or prognosis were investigated. Results HER-2 overexpression and HER-2 amplification (a ratio of HER-2 copies to chromosome 17 [CEP17] copies ≥2.2) were detected in 33.3% (twelve of 36 patients) and 5.6% (two of 36 patients) of primary tumors, respectively. HER-2 overexpression was not associated with clinicopathological factors or prognosis. In 19 tumor specimens obtained from metastatic or recurrent tumors, HER-2 overexpression and HER-2 amplification were detected in 57.9% (eleven patients) and 15.8% (three patients), respectively. HER-2 overexpression tended to predict a worse prognosis. Conclusion HER-2 expression in metastatic or recurrent tumors was more frequent than in matched primary high-grade or type 2 endometrial carcinomas. Trastuzumab in combination with cytotoxic chemotherapy may represent an alternative therapeutic option for these tumors.