HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions

Fusco, Nicola; Guerini-Rocco, Elena; Conte, Claudia Del; Pellegrini, Caterina; Gaetano, Bulfamante; Nuovo, Franca Di; Romagnoli, Solange; Bòsari, Silvano

doi:10.1038/modpathol.2012.228

Cited by 63 publications

(66 citation statements)

References 68 publications

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“…[34][35][36] HER2 status has been reported to be associated with gastric cancer, and HER2 overexpression has been shown to be correlated with decreased overall survival. [37][38][39] Therefore, expression of Rb and HER2 were used in the present study as negative and positive markers, respectively, of neoplastic transformation. …”

Section: Introductionmentioning

confidence: 99%

Addition of all-trans-retinoic acid to omeprazole and sucralfate therapy improves the prognosis of gastric dysplasia

Jia

Xing

et al. 2015

J Int Med Res

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Objective: To investigate the efficacy of all-trans retinoic acid (ATRA) in human gastric dysplasia. Methods: In this double-blind study, patients with precancerous gastric dysplasia with or without intestinal metaplasia (IM) received either conventional treatment consisting of omeprazole and sucralfate (control group) or conventional treatment plus ATRA. Gastric mucosal biopsies were performed before and after drug treatment and were analysed histologically; expression of retinoblastoma (Rb) protein and HER2 protein in gastric mucosa were measured using immunohistochemistry. Results: A total of 122 patients were included in the study, 63 in the ATRA group and 59 in the control group. In the ATRA group, dysplasia was attenuated in 43 out of 63 patients (68%) compared with 22 out of 59 patients (37%) in the control group; however, IM was not affected by treatment in either group. ATRA treatment was associated with significantly increased Rb expression and decreased HER2 expression in gastric mucosa. Conclusions: The use of conventional therapy plus ATRA for gastric dysplasia was associated with improved efficacy compared with conventional therapy alone. It was also accompanied by increased Rb expression and decreased HER2 expression in gastric mucosa. The addition of ATRA to conventional therapy for gastritis may improve the prognosis of gastric dysplasia.

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Section: Introductionmentioning

confidence: 99%

Addition of all-trans-retinoic acid to omeprazole and sucralfate therapy improves the prognosis of gastric dysplasia

Jia

Xing

et al. 2015

J Int Med Res

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“…Compared with excision specimens, the biopsy specimens may overestimate or underestimate HER2 status, and discrepancies may occur not only at the IHC level but also at the FISH level. Discordant HER2 results for paired specimens have been also reported for primary and metastatic carcinoma [25][26][27].…”

Section: Discussionmentioning

confidence: 89%

“…In the current study, discordant paired specimens represented nearly one-third of HER2-positive specimens (either biopsy or excision). HER2 testing of all available specimens is also advocated by other investigators [14,20,26,27]. Until future research determines the survival outcomes of patients with HER2 positivity in biopsy or excision specimens, the above strategy should be used in clinical practice if feasible.…”

Section: Discussionmentioning

confidence: 99%

HER2 testing in paired biopsy and excision specimens of gastric cancer: the reliability of the scoring system and the clinicopathological factors relevant to discordance

Huang

Lee

et al. 2014

Gastric Cancer

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Background Inclusion of trastuzumab in chemotherapy regimens is advantageous for patients with advanced or metastatic gastric cancer who overexpress HER2. Therefore, accurate assessment of HER2 status in tumor tissue is critical when weighing treatment options. Methods We examined HER2 expression in 180 paired endoscopic biopsy and surgical excision specimens of gastric cancers via immunohistochemistry (IHC). Equivocal IHC results (IHC 2?) were resolved by HER2 fluorescence in situ hybridization (FISH). The relationships of several clinical and pathological features with discordant HER2 results in paired specimens were determined. Results Fourteen biopsy specimens and surgical specimens (7.8 %) were HER2-positive. Discordant HER2 IHC scores were observed in 90 paired specimens (50 %) and 8 paired specimens (4.4 %) had discordant results. The kappa coefficients for an HER2 diagnostic algorithm were 0.264, 0.339, and 0.690 for IHC scores, IHC categories, and final results, respectively (p \ 0.001). Discordant HER2 results were significantly associated with discordant tumor differentiation in the paired biopsy and excision specimens (p = 0.01). Intratumoral heterogeneity did not predict HER2 discordance. There was no association between HER2 discordance and the number of biopsy tissue fragments (p = 0.764). Conclusions Hofmann's HER2 scoring system is a fairly reliable tool for evaluating HER2 status in biopsy and excision specimens. Discordant HER2 results in paired specimens were observed in a small percentage of gastric cancers. Testing all available specimens should be considered in order to eliminate discrepancies, especially when discordant tumor differentiation is observed.

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“…We examined the tumor invasive front at the primary sites in resected specimens, as it was previously reported that HER2 staining exhibits no preferential distribution within the tumor, with negligible variation between the tumor mucosal surface and the invasive front (24) and the tumor invasive front is closely involved in the metastatic process. However, Fusco et al (25) reported that there is discordance in the HER2 status between the tumor invasive front and other lesions and gastric cancer is known to exhibit heterogeneous HER2 expression (14,18). Therefore we examined all the sites of the primary tumor in the discordant case to determine whether there was heterogeneity of HER2 expression, in order to assess the discordance between primary and paired metastatic lesions.…”

Section: Discussionmentioning

confidence: 99%

Expression of human epidermal growth factor receptor 2 in primary and paired parenchymal recurrent and/or metastatic sites of gastric cancer

Shibata

Nimura

Hashimoto

et al. 2014

Molecular and Clinical Oncology

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Abstract. Human epidermal growth factor receptor 2 (HER2) status has been evaluated at the primary site of gastric cancer when planning trastuzumab therapy against recurrent or metastatic lesions, since tissue sampling is uncommon in recurrent or metastatic lesions. This study retrospectively investigated the concordance of HER2 expression between primary and metastatic/recurrent lesions in order to confirm sensitivity to trastuzumab. The subjects comprised 37 patients with gastric adenocarcinoma who underwent tissue biopsy or surgical resection of the primary sites and 49 paired synchronous or metachronous metastatic sites (excluding lymph nodes) at the Fukuoka University Hospital between January, 1998 and September, 2012. All the samples were evaluated for HER2 status at the invasive front by immunohistochemistry (IHC). The HER2 positivity rate of the primary sites was ~16% and the concordance ratio of the IHC results between primary and paired metastatic sites was ~97%. No discordant cases regarding HER2 status were found among metachronous interventions for metastatic lesions. Only one patient exhibited conversion from a HER2-negative status in all the portions of the primary site to a positive status in a metastatic site. In conclusion, a high concordance ratio for HER2 status was observed between primary and paired metastatic lesions. Thus, employing trastuzumab therapy against metastatic or recurrent gastric cancer based on the HER2 status of the primary lesion appears to be an acceptable approach.

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HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions

Cited by 63 publications

References 68 publications

Addition of all-trans-retinoic acid to omeprazole and sucralfate therapy improves the prognosis of gastric dysplasia

Addition of all-trans-retinoic acid to omeprazole and sucralfate therapy improves the prognosis of gastric dysplasia

HER2 testing in paired biopsy and excision specimens of gastric cancer: the reliability of the scoring system and the clinicopathological factors relevant to discordance

Expression of human epidermal growth factor receptor 2 in primary and paired parenchymal recurrent and/or metastatic sites of gastric cancer

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