Prognostic significance of c-erbB-2/HER2 expression in advanced uterine cervical carcinoma with para-aortic lymph node metastasis treated with radiation therapy

Abstract

This paper looks at whether c-erbB-2/HER2 expression in uterine cervical carcinoma before treatment is a predictive parameter of prognosis in patients with para-aortic lymph node metastasis (PALN) in advanced disease after treatment with radiation therapy (RT). Twenty-one patients with PALN at the first visit and/or during follow-up and treated with RT for PALN lesions were studied. Their clinical stages were IIIB or greater and they were referred to the National Institute of Radiological Sciences Hospital for RT between 1987 and 1995. They consisted of 12 patients with PALN detected at the first visit and nine with PALN detected during the follow-up period. All patients had no distant metastasis except PALN. They were treated with a combination of external whole pelvis and intracavitary irradiation to the primary pelvic lesions. The PALN was treated with external irradiation alone with anterior-posterior parallel opposed fields and anterior oblique fields or anterior-posterior parallel opposed oblique fields. The average total dose to PALN was 53.3 Gy (40–61Gy). Tissue samples were obtained from cervical tumors (primary lesions) before RT. Immunohistochemical staining was performed using anti-c-erbB-2/HER2 monoclonal antibody for conventional paraffin sections. c-erbB-2/HER2 positive staining was observed in cancer membrane and cytoplasm. Nine specimens were positive for c-erb-B2/HER2 and the total positive rate was 43%. The 5-year survival rate was 38% for all patients. The 5-year survival rate of the c-erbB-2/HER2 positive patients was 28%, representing a trend toward poorer prognosis than the 52% of negative patients (P= 0.10). Multivariate analysis using Cox proportional hazards model showed that c-erbB-2/HER2 was an independent prognostic factor (P = 0.024). The present study suggests that c-erbB-2/HER2 expression of cervical tumors might be a predictive parameter of prognosis after radiation therapy for PALN of very advanced uterine cervical carcinoma patients.

HER2/neu (c‐erbB‐2) gene amplification and protein expression are rare in uterine cervical neoplasia: a tissue microarray study of 814 archival specimens

“…We found that expression of the HER2 ⁄ neu oncoprotein and HER2 ⁄ neu gene amplification are uncommon events in cervical neoplasia. This contrasts with a number of previous publications in the literature, including reports of a correlation between HER2 ⁄ neu overexpression and poor response to radiotherapy and worse overall survival (11,24,25).…”

HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival

“…24 In patients with cervical carcinoma, a relation has been shown between HER-2 expression and local resistance to radiotherapy as well as between HER-2 expression and prognosis. [25][26][27] In a study by Akamatsu et al, 28 HER-2 expression in patients with esophageal carcinoma was associated with local resistance to chemo-radiotherapy but not linked with prognosis. Furthermore, the authors reported that tumors with HER-2 expression were resistant to cisplatinumbased chemotherapy.…”

Supraclavicular lymph node metastases of unknown origin: HPV-typing identifies the primary tumour

“…Aside from local invasion, lymphatic cell spread from the primary cervical lesion sequentially leads to pelvic, paraaortic and supraclavicular lymph node metastases. The incidence of paraaortic lymph node metastases increases with tumour stage (IB 6%; IIB 19%; IIIB 29%; V 30%) (Nibe et al 2003;Ahmed et al 2004). The Gynecologic Oncology Group identified paraaortic lymph node metastases and tumour size as the two most significant prognostic factors regarding survival (Singh et al 2003).…”

“…Furthermore, lymph node metastases have major impact on the risk of local and distant cancer recurrence as well as disease-specific survival (Munkarah 2002). Five-year survival rates in patients with paraaortic lymph node metastases treated with standard-fraction irradiation range between 15% and 50% (Kupets et al 2002;Nibe et al 2003;Ahmed et al 2004). The overall frequency of left supraclavicular lymph node metastases is less than 5%.…”