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discussion
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This therapeutic option proved useful in extending the survival of breast cancer patients, particularly when selected by FISH (Mass et al, >>2005<<). Since then, interest in applying this approach to other malignancies with ERBB2 amplification has increased. The first goal of this study was to clarify the frequency of ERBB2 overexpression and amplification in a large series of
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Moreover, both techniques allow for the specific detection of ERBB2 alteration in individual cells, while maintaining critical architectural tissue information (Pauletti et al, >>2000<<).
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Kim et al (>>2007<<) reported 22.6% of carcinomas overexpressing ERBB2 protein (2+ or 3+), but only 7.7% showed gene amplification.
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Takehana et al (>>2002<<) also found ERBB2 amplification in all gastric carcinoma cases scored as 3+.
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On the other hand, Park et al (>>2006<<) found ERBB2 amplification in only 45% of the carcinomas scored as 3+, which might be due to the low specificity of the antibody used.
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Similarly, Kim et al (>>2007<<) found ERBB2 amplification in 4% of the 1+ gastric carcinomas analysed by FISH.
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Most of the studies that reported the absence of gene amplification in carcinomas classified as 1+ did not analyse all 1+ carcinomas (Takehana et al, >>2002<<; Park et al, 2006).
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Most of the studies that reported the absence of gene amplification in carcinomas classified as 1+ did not analyse all 1+ carcinomas (Takehana et al, 2002; Park et al, >>2006<<). As for the 18 gastric carcinomas classified as 2+ in this study, 12 (66.6%) showed ERBB2 amplification and four of the remaining six presented chromosome 17 polisomy. The correlation between 2+ carcinomas and ERBB2 amplification is
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Some genetic alterations are exclusive of given subtypes of gastric carcinomas, as exemplified by CDH1 mutations in diffuse gastric carcinomas (Becker et al, >>1994<<; Grady et al, 2000). Several authors have earlier stated that ERBB2 amplification is an exclusive event of intestinal-type gastric carcinomas (Takehana et al, 2002; Varis et al, 2004).
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Some genetic alterations are exclusive of given subtypes of gastric carcinomas, as exemplified by CDH1 mutations in diffuse gastric carcinomas (Becker et al, 1994; Grady et al, >>2000<<). Several authors have earlier stated that ERBB2 amplification is an exclusive event of intestinal-type gastric carcinomas (Takehana et al, 2002; Varis et al, 2004).
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Several authors have earlier stated that ERBB2 amplification is an exclusive event of intestinal-type gastric carcinomas (Takehana et al, >>2002<<; Varis et al, 2004).
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Several authors have earlier stated that ERBB2 amplification is an exclusive event of intestinal-type gastric carcinomas (Takehana et al, 2002; Varis et al, >>2004<<). However, of the 38 carcinomas with amplification detected by FISH, three were diffuse and four were not classifiable by Lauren. Other authors reported that diffuse gastric carcinomas account for 5–6.2% of all ERBB2-amplified carcinomas
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Other authors reported that diffuse gastric carcinomas account for 5–6.2% of all ERBB2-amplified carcinomas (Tanner et al, >>2005<<; Park et al, 2006; Kim et al, 2007), which is corroborated by our findings.
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Other authors reported that diffuse gastric carcinomas account for 5–6.2% of all ERBB2-amplified carcinomas (Tanner et al, 2005; Park et al, >>2006<<; Kim et al, 2007), which is corroborated by our findings.
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Other authors reported that diffuse gastric carcinomas account for 5–6.2% of all ERBB2-amplified carcinomas (Tanner et al, 2005; Park et al, 2006; Kim et al, >>2007<<), which is corroborated by our findings.
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Interestingly, in both Western and Eastern patients there is a correlation between gastric carcinomas with ERBB2 amplification and intestinal type: 81.6% in this study vs 86 and 84.2% reported in Eastern patients (Park et al, >>2006<<; Kim et al, 2007).
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in both Western and Eastern patients there is a correlation between gastric carcinomas with ERBB2 amplification and intestinal type: 81.6% in this study vs 86 and 84.2% reported in Eastern patients (Park et al, 2006; Kim et al, >>2007<<).
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This hypothesis is supported by Carvalho et al (>>2006<<), who studied by array-comparative genome hybridisation 12 mixed carcinomas.
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Furthermore, in our consecutive series of gastric cancer patients, we found ERBB2 amplification in two early gastric carcinomas (stage IA), as reported earlier in similar studies (David et al, >>1992<<; Ooi et al, 1998; Park et al, 2006; Kim et al, 2007), further supporting the idea that ERBB2 amplification may occur at an early stage in gastric carcinogenesis.
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Furthermore, in our consecutive series of gastric cancer patients, we found ERBB2 amplification in two early gastric carcinomas (stage IA), as reported earlier in similar studies (David et al, 1992; Ooi et al, >>1998<<; Park et al, 2006; Kim et al, 2007), further supporting the idea that ERBB2 amplification may occur at an early stage in gastric carcinogenesis.
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Furthermore, in our consecutive series of gastric cancer patients, we found ERBB2 amplification in two early gastric carcinomas (stage IA), as reported earlier in similar studies (David et al, 1992; Ooi et al, 1998; Park et al, >>2006<<; Kim et al, 2007), further supporting the idea that ERBB2 amplification may occur at an early stage in gastric carcinogenesis.
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in our consecutive series of gastric cancer patients, we found ERBB2 amplification in two early gastric carcinomas (stage IA), as reported earlier in similar studies (David et al, 1992; Ooi et al, 1998; Park et al, 2006; Kim et al, >>2007<<), further supporting the idea that ERBB2 amplification may occur at an early stage in gastric carcinogenesis.
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According to Ming (>>1977<<), expansive carcinomas grow by enlargement of cohesive tumour nodules or masses, with a well-defined tumour boundary.
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This infiltrative characteristic might explain why some authors found that this type of growth pattern was associated with worse prognosis (Davessar et al, >>1990<<; Cimerman et al, 1994; Luebke et al, 2005).
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This infiltrative characteristic might explain why some authors found that this type of growth pattern was associated with worse prognosis (Davessar et al, 1990; Cimerman et al, >>1994<<; Luebke et al, 2005).
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This infiltrative characteristic might explain why some authors found that this type of growth pattern was associated with worse prognosis (Davessar et al, 1990; Cimerman et al, 1994; Luebke et al, >>2005<<). Our survival analysis showed that ERBB2-amplifying expansive carcinomas have worse prognosis than those with the same growth pattern lacking that genetic alteration (P=0.011), which we did not observe in infiltrating gastric carcinomas
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Recent data published by Wolf-Yadlin et al (>>2006<<) might explain the different effect of ERBB2 amplification in carcinomas with different growth patterns.
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These authors suggested that ERBB2 overexpression promotes increased cell migration but has minimal effect on cell proliferation in cells stimulated by epidermal growth factor or heregulin (Wolf-Yadlin et al, >>2006<<). Thus, ERBB2 amplification could increase cell migration in expansive carcinomas, whereas infiltrative carcinomas, which already have a strong invasive potential, do not acquire additional advantage from ERBB2 amplification. A similar
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A similar reasoning may explain our observation of a trend to worse 10-year survival among ERBB2-amplified node-negative gastric carcinomas, something that was also reported by others in breast carcinomas (Pauletti et al, >>2000<<).
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