P-0182 - HER 2/neu over-expression represents a prognostic relevant drugable target in liver metastases of colorectal cancer

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Melanie Zoller
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors M. Zoller1, T. Singer2
  • 1Universitiy of Munich, LMU, Clinic Großhadern Department of Surgery, Munich/DE
  • 2University of Munich, LMU, Clinic Großhadern, Department of Surgery, Munich/DE

Abstract

Introduction

In contrast to primary colorectal cancer (CRC), molecular characteristics of the metastatic lesions are currently not considered in therapeutic strategies, although it is well documented that tumour progression is associated with a variety of changes in tumour biology. Hepatic metastasis is the most frequent metastatic lesion in CRC. 20-25% of the patients reveal liver metastases at the time of primary diagnosis, additional 40-50% develop hepatic metastases in the follow up even under chemotherapeutic treatment. In this advanced stage new therapeutic options are urgently needed. The present study aimed to evaluate the prognostic and predictive impact of Her2/neu expression in primary CRC and liver metastasis.

Methods

Cryosections obtained from 89 primary colorectal cancers and 58 liver metastases were immunohistochemically characterized for Her2/neu expression. FISH analysis was performed to identify Her2/neu amplification. Expression pattern was correlated with a number of clinical, pathological and tumorbiological factors using Fishers exact test. The impact of Her2/neu expression on survival was analyzed with Kaplan Meier survival analysis and the multivariate Cox regression analysis.

Results

Her2/neu Score3+ was found in 33.3% of the primary colorectal cancers. Her2/neu Score3+ cancer cells were preferentially found in female patients (women, Score3 + : 25.64%; men, Score3 + : 6.0%, p = 0.014). Moreover, Her2/neu Score3+ tumours were localized more frequently in the left-sided bowel, i.e. colon descendens, sigma and rectum higher than 10cm ab ano (left-sided, Score3 + : 25.53%; right-sided, Score3 + : 2.38%, p = 0.002). None of the primary tumor samples revealed Her2/neu amplification. In primary colorectal cancer Kaplan-Meier analysis revealed no impact of the Her2/neu Score3+ expression on survival. Her2/neu Score3+ was found in 50% of liver metastases. No correlations were obtained between the Her2/neu Score3+ and clinicopathological or tumourbiological characteristics. Comparison between untreated and pretreated liver metastases showed no difference in Her2/neu expression pattern and scoring (p = 0.349), although a number of different chemotherapeutic and biological treatments was performed. Similar as described in the primary tumors Her2/neu was not amplified in the metastatic lesions. Kaplan-Meier analysis showed that Her2/neu Score3+ expressing liver metastases correlated with short survival (p = 0.026). Cox regression analysis confirmed Her2/neu Score3+ status as an independent factor indicating short survival (p = 0.035).

Conclusion

Her2/neu Score3 expression represents a biomarker for patient stratification and might have an impact on future treatment decisions in advanced CRC. Patient subgroups, namely female patients and patients with a left-sided CRC might preferentially benefit from Trastuzumab therapy. Because of the broad range of the fraction of Her2/neu positive cancer cells, decision for Trastuzumab treatment needs to be individualized. Liver metastases rather than primary tumors might be considered to guide drug selection based on Her2/neu Score3 expression.