Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients

Abstract

The clinical significance of ERBB2 amplification/overexpression in gastric cancer remains unclear. In this study, we evaluated the ERBB2 status in 463 gastric carcinomas using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), and compared the findings with histopathological characteristics and with disease-specific survival. ERBB2 overexpression (2 þ and 3 þ ) and amplification (ratio ERBB2/CEP17X2) were found in 43 (9.3%) and 38 (8.2%) gastric carcinomas, respectively. Perfect IHC/FISH correlation was found for the 19 cases scored as 0 (all negative by FISH), and also for the 25 cases scored as 3 þ (all positive by FISH). One out of six carcinomas scored as 1 þ and 12 out of 18 carcinomas scored as 2 þ were positive by FISH. ERBB2 amplification was associated with gastric carcinomas of intestinal type (P ¼ 0.007) and with an expansive growth pattern (P ¼ 0.021). ERBB2 amplification was detected in both histological components of two mixed carcinomas, indicating a common clonal origin. A statistically significant association was found between ERBB2 amplification and worse survival in patients with expansive gastric carcinomas (P ¼ 0.011). We conclude that ERBB2 status may have clinical significance in subsets of gastric cancer patients, and that further studies are warranted to evaluate whether patients whose gastric carcinomas present ERBB2 amplification/overexpression may benefit from therapy targeting this surface receptor. Despite the trend for decreasing incidence, gastric adenocarcinoma is still the second cause of cancer death worldwide (Parkin et al, 2005). The overall 5-year survival rate of patients with resectable gastric cancer ranges from 10 to 30% (Harrison et al, 1998;Msika et al, 2000;Green et al, 2002). Apart from surgical resection, evaluation of available therapies, both neo-adjuvant and adjuvant, provides conflicting results regarding the clinical outcome. Several meta-analyses have been published in an attempt to address the discrepancies reported in the literature, but recommendation for adjuvant chemotherapy in Western centres is still not consensual (Hermans et al, 1993;Earle and Maroun, 1999;Mari et al, 2000;Gianni et al, 2001;Janunger et al, 2001Janunger et al, , 2002Hu et al, 2002). The most important prognostic factor established for gastric cancer is the TNM stage, which is determined by the depth of invasion, involvement of lymph nodes, and distant metastasis. However, clinical outcome varies among patients in the same stage (Park et al, 2006). Therefore prognostic factors other than the TNM stage, as well as new therapies, would be of great value for gastric cancer patients.The ERBB2 gene maps to 17q12 -q21 and encodes a 185-kDa transmembrane tyrosine kinase receptor (p185), which is a member of the epidermal growth factor receptor family (Xu et al, 1984;Akiyama et al, 1986;Popescu et al, 1989). In breast carcinomas, ERBB2 functions as an oncogene, as amplification of the gene induces protein overexpression in the cell membrane (Slamon et al, 1989). Besides ...

Immunohistochemical Expression of Her2 in Adenocarcinoma of the Stomach

“…Regarding anatomical location similar finding have been reported, with no difference between proximal and distal tumor, as we have found in our study (3,9,10,14,18,21) . Most studies conducted in Asia have also reported reactivity rates of 11.7% to 15.74%, similar to our findings, as well as the predominance of HER2 expression in the intestinal subtype (11,16,17,22) .…”

Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer

“…Among patients with AGC, the rate of human epidermal growth factor receptor 2 (HER2) positivity reportedly ranges from 8.2 to 23.0% as assessed by immunohistochemistry (IHC), and from 7.1 to 27.1% when assessed by fluorescence in situ hybridization (FISH) (12)(13)(14)(15). On the basis of the Trastuzumab for Gastric Cancer (ToGA) trial results, addition of trastuzumab to platinum-based chemotherapy has become the standard first-line therapy for HER2-positive AGC (16).…”

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“…Not specified Wang et al, 10 Im et al 27 [2 Studies] Marx et al, 15 Yu et al, 19 Hayashi et al, 22 Satiroglu-Tufan et al, 25 Ghaderi et al, 36 Allgayer et al 39 15 Barros-Silva et al, 16 Hayashi et al, 22 Park et al, 24 Tanner et al, 26 Song et al, 30 Garcia et al, 31 Lee et al, 32 Pintode-Sousa et al, 34 Oshima et al 38 [12 Studies (2 studies between 1990 and 1999 not displayed)]…”

“…III/IV Wang et al, 10 Zhang et al, 18 Im et al, 27 Ghaderi et al, 36 Allgayer et al 39 [5 Studies] Presence of microvascular invasion Wang et al, 10 Pinto-de-Sousa et al, 34 Allgayer et al 39 [3 Studies] Grabsch et al, 11 Barros-Silva et al, 16 Park et al, 24 Garcia et al 31 [8 Studies (4 studies between 1990 and 1999 not displayed)]…”