Frequency of HER-2 Positivity in Rectal Cancer and Prognosis

Abstract

In patients with advanced rectal cancer (cUICC II and III) multimodality therapy resulted in better long-term local tumor control. Ongoing clinical trials are focusing on therapy intensification to improve disease-free (DFS) and cancer-specific survival (CSS), the integration of biomarkers for prediction of individual recurrence risk, and the identification of new targets. In this context, we investigated HER-2, a member of the epidermal growth factor receptor family, whose expression pattern and role was unclear in rectal cancer. A total of 264 patients (192 male, 72 female; median age 64 y) received standardized multidisciplinary treatment according to protocols of phase II/III trials of the German Rectal Cancer Study Group. HER-2 status was determined in pretherapeutic biopsies and resection specimens using immunohistochemistry scoring and detection of silver in situ hybridization amplification. Tumors with an immunohistochemistry score of 3 or silver in situ hybridization ratios of ≥2.0 were classified HER-2 positive; these results were correlated with clinicopathologic parameters [eg, resection (R) status, nodal status ((y)pN)], DFS, and CSS. Positive HER-2 status was found in 12.4% of biopsies and in 26.7% of resected specimens. With a median follow-up of 46.5 months, patients with HER-2 positivity showed in trend a better DFS (P=0.1) and a benefit in CSS (P=0.03). The 5-year survival rate was 96.0% (HER-2 positive) versus 80.0% (HER-2 negative). In univariate and multivariate analyses, HER-2 was an independent predictor for CSS (0.02) along with the (y)pN status (P<0.00001) and R status (P=0.011). HER-2 amplification is detectable in a relevant proportion (26.7%) of rectal cancer patients. For the development of innovative new therapies, HER-2 may represent a promising target and should be further assessed within prospective clinical trials.

Lack of Effects of HER-2/neu on Prognosis in Colorectal Cancer: a Meta-analysis

“…Out of these excluded studies, one shared the same population with another study , two analyzed HER-2/neu expression in serum (Tsigris et al, 2002;Kovacevic et al, 2007), and patients number of HER-2/neu overexpression of one was less than three (Pappas et al, 2013). Finally, 17 eligible studies were included into this meta-analysis (Kay et al, 1994;Kapitanovic et al, 1997;Osako et al, 1998;Knosel et al, 2002;McKay et al, 2002;Rossi et al, 2002;Sanz-Casla et al, 2004;Essapen et al, 2004;Jesus et al, 2005;Uner et al, 2005;Schuell et al, 2006;Park et al, 2007;Kavanagh et al, 2009;Li et al, 2011;Conradi et al, 2013;Lim et al, 2013). Figure 1 shows a flowchart of the literature selection process.…”

HER-2 overexpression and survival in colorectal cancer: a meta-analysis

“…However, the more likely reason may be the various scoring systems used, considering that four different criteria were reported in the five studies of the Asian subgroup. In addition, it is worth noting that Conradi et al (2013) showed that HER-2 overexpression was a good predictive factor. They reported that patients with HER-2 positivity showed a trend towards a better disease-free survival and a benefit in cancer-specific survival, and the 5-year survival rate was 96.0% (HER-2 positive) versus 80.0% (HER-2 negative).…”

“…Five different cut-off values were used to determine HER-2 status, of which the HercepTest scoring system was the most frequently adopted (n=5). As for prognostic value, five studies identified HER-2 overexpression as an indicator of poor prognosis (Osako et al, 1998;Park et al, 2007;Baiocchi et al, 2009;Chen et al, 2010;Lu et al, 2012), five studies revealed that HER-2 overexpression had no influence on CRC survival (McKay et al, 2002;Rossi et al, 2002;Jesus et al, 2005;Kavanagh et al, 2009;Li et al, 2011), and one study reported HER-2 overexpression to be a good predictor (Conradi et al, 2013) (Table 2).…”

“…Some studies reported that HER-2 overexpression was a poor predictor (Osako et al, 1998;Park et al, 2007;Baiocchi et al, 2009;Chen et al, 2010;Lu et al, 2012), while others reported that it was negatively related to patient survival (McKay et al, 2002;Rossi et al, 2002;Jesus et al, 2005;Kavanagh et al, 2009;Li et al, 2011). Still others reported that HER-2 was a good predictor (Conradi et al, 2013). Therefore, we performed a systematic meta-analysis of all available studies using rigorous methods aiming to quantitatively estimate the prognostic value of HER-2 overexpression in CRC.…”

Rektumkarzinom – Besondere Aspekte der Pathologie

“…Einige seltene histologische Subtypen wie das muzinöse Adenokarzinom und das rhabdoide Karzinom haben eine ungünstigere Prognose und sprechen schlecht auf eine präoperative Radiochemotherapie an. Zu den näher untersuchten und immunhistochemisch im Gewebe bestimmbaren Parametern mit potenzieller Relevanz zählen HER-2 [4], Thymidilatsynthase [29], Survivin [27], Topoisomerase I [13], Amphiregulin (AREG) und ERCC1 [25]. Für einige dieser Marker wurde eine Korrelation mit dem Ansprechen auf bestimmte Pharmaka beschrieben.…”