Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression: a multicentre immunohistochemical study in the Asia–Pacific region

Putti, Thomas C.; To, Ka‐Fai; Hsu, Hey‐Chi; Chan, Anthony T.C.; Lai, Gingming; Tse, Gmk; Lee, Yoke Sun; Whang‐Peng, Jacqueline; Millward, M. J.; Lin, Li‐Ching; Lin, Xiao; Lee, Cheok Soon

doi:10.1046/j.1365-2559.2002.01436.x

Cited by 61 publications

(55 citation statements)

References 30 publications

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“…Moreover, EGFR overexpression has been reported to be a highly significant and independent indicator of prognosis in HNSCC patients; EGFR protein levels in primary head and neck tumors were also found to be associated with decreased disease-free and cause-specific overall survival [20,21]. In disagreement with these reports, we did not observe a significant association between EGFR overexpression and disease progression in our patient cohort.…”

Section: Discussioncontrasting

confidence: 97%

“…Furthermore, it has been shown previously that of all the members of the HER family, HER2 was the most sig-26 ORL 2004;66: [21][22][23][24][25][26] Schartinger/Kacani/Andrle/Schwentner/ Wurm/Obrist/Oberaigner/Sprinzl nificant factor in predicting outcome in HNSCC patients [22]. In our patient cohort, a statistically significant correlation between HER2 expression and decreased overall survival was demonstrated (p = 0.013).…”

Section: Discussionmentioning

confidence: 97%

“…EGFR expression in head and neck squamous cell carcinoma (HNSCC) has been reported in approximately 90% of specimens; it is associ-22 ORL 2004;66: [21][22][23][24][25][26] Schartinger/Kacani/Andrle/Schwentner/ Wurm/Obrist/Oberaigner/Sprinzl ated with poor prognosis [4,5]. The HER2/neu oncoprotein has been most extensively characterized in breast cancer, where its expression correlates with poor prognosis and resistance to chemotherapeutic agents [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacodiagnostic Value of the HER Family in Head and Neck Squamous Cell Carcinoma

Schartinger¹,

Kacani²,

Andrle³

et al. 2004

ORL

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Two protooncogene products, EGFR (Her-1, c-erbB-1) and HER2 (Her-2/neu, c-erbB-2), have been reported to be frequently overexpressed in head and neck squamous cell carcinoma (HNSCC). In order to identify patients who may benefit from targeted cancer treatment for these two molecules, we determined the expression status of EGFR and HER2 in 129 HNSCC tumor specimens. Two pharmacodiagnostic kits (EGFR pharmDx™ and HercepTest™) were used to identify HNSCC tumors that overexpress EGFR or HER2. Overexpression of EGFR was detected in 42.6% of the tumor specimens, while HER2 was only rarely expressed (overexpression was observed in just 3.1% of all cases). Given the necessity of new therapeutic modalities for patients suffering from HNSCC, treatment EGFR signaling inhibitors appears to be warranted, whereas therapeutic intervention with HER2 inhibitors seems to be inappropriate in this tumor type.

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Section: Discussioncontrasting

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Pharmacodiagnostic Value of the HER Family in Head and Neck Squamous Cell Carcinoma

Schartinger¹,

Kacani²,

Andrle³

et al. 2004

ORL

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“…[28][29][30][31][32] Immunohistochemical assessment of EGFR expression in fixed, paraffin-embedded specimens has also been used with some success. 33,[37][38][39][40][41][42][43] However, real time, in vivo evaluation of EGFR expression would yield important clinical advantages for diagnosis and treatment monitoring of epithelial lesions. In our study, we localized EGFR expression in whole 200-lm thick fresh tissue sections, as an initial step toward this goal of in vivo molecular imaging.…”

Section: Discussionmentioning

confidence: 99%

Real‐time detection of epidermal growth factor receptor expression in fresh oral cavity biopsies using a molecular‐specific contrast agent

Hsu

Gillenwater²,

Hasan

et al. 2006

Intl Journal of Cancer

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Early diagnosis of individuals with high risk of developing head and neck squamous carcinoma should lead to decreased morbidity and increased survival. To aid in noninvasive early detection of oral neoplasia in vivo, we have developed a molecular-specific fluorescent contrast agent, consisting of a far-red fluorescent dye coupled to a monoclonal antibody targeted against the epidermal growth factor receptor. In our study, we used organ cultures of normal and neoplastic human oral tissue to evaluate the capabilities of using this contrast agent to enhance clinical diagnosis. Fresh tissue sections were prepared from 34 biopsies of clinically normal and abnormal oral mucosa from 17 consenting patients. Samples were exposed to contrast agent, rinsed and the presence of bound agent was detected using fluorescence confocal microscopy. Simple assays to assess cytotoxicity of the dye used in the agent and to determine labeling efficacy at physiologic temperatures were also performed. Results indicate that the mean fluorescence intensity (MFI) of samples with dysplasia and cancer are higher than that of the normal sample from the same patient, and that this increase in fluorescence could potentially be used in the early detection and delineation of premalignant lesions. Normal tissue could be distinguished from cancer or moderate dysplasia, using either the ratio of the MFI of abnormal to normal tissue or the MFI obtained from the epithelial surface. No detrimental effects from the dye were observed over a 4-day period. These results indicate that the use of this optical contrast agent could yield important clinical advantages for noninvasive early detection and molecular characterization of oral mucosa. ' 2006 Wiley-Liss, Inc.Key words: fluorescent contrast agent; epidermal growth factor receptor; molecular-specific contrast agentThe 5-year survival rate for oral cancer has not improved significantly in the last 3 decades, despite numerous advances in treatment modalities.

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“…Among these pathways, the epidermal growth factor receptor (EGFR) has been the most widely studied. Overexpression of EGFR protein occurs in approximately 70% to 80% of HNSCC tumors, [5][6][7] the gene encoding EGFR is amplified in 17% to 31% of patient tumors, 8 -10 and high levels of the receptor have been correlated with poor prognosis. 8,10,11 Abnormal signaling through the EGFR has been implicated in the activation of downstream pathways [ie, phosphatidylinositol 3-kinase/Akt and Ras/ Raf/mitogen-activated ERK kinase (MEK)/extracellular signal-regulated kinase (ERK)] in HNSCC.…”

mentioning

confidence: 99%

Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples

Frederick

VanMeter

Gadhikar

et al. 2011

The American Journal of Pathology

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Molecular targeted therapy represents a promising new strategy for treating cancers because many smallmolecule inhibitors targeting protein kinases have recently become available. Reverse-phase protein microarrays (RPPAs) are a useful platform for identifying dysregulated signaling pathways in tumors and can provide insight into patient-specific differences. In the present study, RPPAs were used to examine 60 protein end points (predominantly phosphoproteins) in matched tumor and nonmalignant biopsy specimens from 23 patients with head and neck squamous cell carcinoma to characterize the cancer phosphoproteome. RPPA identified 18 of 60 analytes globally elevated in tumors versus healthy tissue and 17 of 60 analytes that were decreased. The most significantly elevated analytes in tumor were checkpoint kinase (Chk) 1 serine 345 (S345), Chk 2 S33/35, eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) S65, protein kinase C (PKC) / threonine 410/412 (T410/T412), LKB1 S334, inhibitor of kappaB alpha (IB-␣) S32, eukaryotic translation initiation factor 4E (eIF4E) S209, Smad2 S465/67, insulin receptor substrate 1 (IRS-1) S612, mitogen-activated ERK kinase 1/2 (MEK1/2) S217/221, and total PKC . To our knowledge, this is the first report of elevated PKC in head and neck squamous cell carcinoma that may have significance because PKC is an oncogene in several other tumor types, including lung cancer. The feasibility of using RPPA for developing theranostic tests to guide personalized therapy is discussed in the context of these data.

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Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression: a multicentre immunohistochemical study in the Asia–Pacific region

Cited by 61 publications

References 30 publications

Pharmacodiagnostic Value of the HER Family in Head and Neck Squamous Cell Carcinoma

Pharmacodiagnostic Value of the HER Family in Head and Neck Squamous Cell Carcinoma

Real‐time detection of epidermal growth factor receptor expression in fresh oral cavity biopsies using a molecular‐specific contrast agent

Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples

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