Prognostic impact of <i>HER‐2/neu</i> expression on squamous head and neck carcinomas

Cavalot, A; Martone, Tiziana; Roggero, Nicolò; Brondino, Gabriele; Pagano, Mario; Cortesina, G

doi:10.1002/hed.20574

Cited by 72 publications

(73 citation statements)

References 42 publications

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“…6B). Notably, HER-2 has been suggested as an oncogene/tumor marker for OSCC in previous studies (25,26). In our mouse tumor study, we also identified significant expression levels of HER-2 in mouse oral tumors.…”

Section: Resultssupporting

confidence: 75%

Functional Genomic Analysis Identified Epidermal Growth Factor Receptor Activation as the Most Common Genetic Event in Oral Squamous Cell Carcinoma

et al. 2009

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A 250K single-nucleotide polymorphism array was used to study subchromosomal alterations in oral squamous cell carcinoma (OSCC). The most frequent amplification was found at 7p11.2 in 9 of 29 (31%) oral cancer patients. Minimal genomic mapping verified a unique amplicon spanning from 54.6 to 55.3 Mb on chromosome 7, which contains SEC61G and epidermal growth factor receptor (EGFR). Results from fluorescence in situ hybridization, transcriptome, and immunohistochemistry analyses indicated that the expression level of EGFR , but not of SEC61G, was up-regulated and tightly correlated with DNA copy number in 7p11.2 amplified tumors. Among the members of the erbB family, EGFR (HER1) was found to be the most frequently amplified and highly expressed gene in both human and mouse oral tumors (P < 0.01). Genes for downstream effectors of EGFR, including KRAS, mitogen-activated protein kinase 1, and CCND1, were also found amplified or mutated, which resulted in activation of EGFR signaling in 55% of OSCC patients. Head and neck squamous cancer cells with different EGFR expression levels showed differential sensitivity to antitumor effects of AG1478, a potent EGFR inhibitor. AG1478-induced EGFR inactivation significantly suppressed tumor development and progression in a mouse oral cancer model. Our data suggest that EGFR signaling is important in oral cancer development and that anti-EGFR therapy would benefit patients who carry the 7p11.2 amplicon in their tumors.

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Section: Resultssupporting

confidence: 75%

Functional Genomic Analysis Identified Epidermal Growth Factor Receptor Activation as the Most Common Genetic Event in Oral Squamous Cell Carcinoma

et al. 2009

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“…13,14 Head and neck cancers have been associated with EGFR family proteins and signal transduction molecules downstream. [15][16][17][18][19][20] Hence it is a relevant to use anti-EGFR based therapy in addition to the standard of care prevalent. 5,13,21 Overall in this study, the mR3 antibody showed a similar recognition profile to the EGFR Santa Cruz antibody, but they were not identical (Fig.…”

mentioning

confidence: 99%

Nimotuzumab with chemoradiation confers a survival advantage in treatment-naïve head and neck tumors over expressing EGFR

Basavaraj

Sierra²,

Shivu³

et al. 2010

Cancer Biology & Therapy

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“…A marked Her-2/neu membranous overexpression was already found in other endocrine tumors including papillary thyroid [36], pheochromocytomas [37], and small cell lung carcinomas [38] as well as in nonendocrine tumors including those of esophagus [8], stomach [8,39], breast [40], head and neck [41], colon [8,42], and ovary [43]. In all these studies, HER-2/neu overexpression inversely correlates with survival and directly with increased invasiveness and aggressive growth, representing an important prognostic factor for many human tumors.…”

Section: Discussionmentioning

confidence: 99%

Involvement of HER-2/neu and metastasis-related proteins in the development of ileal neuroendocrine tumors

et al. 2011

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HER-2/neu overexpression and/or gene amplification occurs in several human malignancies, frequently correlates with tumor aggressiveness, and provides the basis for treatment with trastuzumab. Among neuroendocrine neoplasms (NEN) of the gastroenteropancreatic (GEP) tract, ileal neuroendocrine tumors show peculiar features of malignancy with frequent metastases at the diagnosis. We investigated the overexpression and/or amplification of HER-2/neu and the involvement of the metastasis-related proteins c-Met, MTA-1, and VEGF in 24 primary ileal NEN by immunohistochemistry and fluorescence in situ hybridization (FISH). Data were compared with those of 43 GEP endocrine tumors of other sites. All primary ileal NEN showed an intense membranous and cytoplasmic immunostaining for HER-2/neu. According to the breast cancer scoring system, 17% of ileal carcinoids showed a score of 3+ and 71% with a score of 2+ with a significant difference respect the non-ileal GEP endocrine tumors (p < 0.0000). FISH analysis revealed chromosome 17 polysomy in 33% of 2+/3+ ileal tumors but not HER-2/neu gene amplification. The c-Met and MTA-1 but not VEGF were overexpressed in almost all ileal NEN, whereas VEGF presented more frequently a normal staining. The comparisons with the other GEP NEN demonstrated significant differences for all the three proteins (p < 0.0000, p < 0.0002, and p < 0.001, respectively). These findings suggest that in ileal NEN, HER-2/neu overexpression plays a role in the carcinogenetic process and by triggering the altered expression of c-Met and MTA-1, may activate the molecular pathway(s) promoting tumor progression and metastasis development. Ileal HER-2/neu overexpressing neuroendrocrine tumors may constitute potential candidates for target therapy with specific humanized monoclonal antibodies.

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Prognostic impact of HER‐2/neu expression on squamous head and neck carcinomas

Abstract: HER2/neu overexpression and its relationship with survival suggest that new therapeutic approaches targeting epidermal growth factor receptor (EGFR) family receptors could provide a new way of treating HNSCC patients with HER2/neu-positive neoplastic lesions.

Cited by 72 publications

References 42 publications

Functional Genomic Analysis Identified Epidermal Growth Factor Receptor Activation as the Most Common Genetic Event in Oral Squamous Cell Carcinoma

Functional Genomic Analysis Identified Epidermal Growth Factor Receptor Activation as the Most Common Genetic Event in Oral Squamous Cell Carcinoma

Nimotuzumab with chemoradiation confers a survival advantage in treatment-naïve head and neck tumors over expressing EGFR

Involvement of HER-2/neu and metastasis-related proteins in the development of ileal neuroendocrine tumors

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