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

Schartinger, Volker Hans; Kacani, Laco; Andrle, J; Schwentner, Ilona; Wurm, Martin; Obrist, Peter; Oberaigner, Wilhelm; Sprinzl, Georg Mathias

doi:10.1159/000077229

Cited by 21 publications

(20 citation statements)

References 18 publications

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“…Thus, it was suggested as a marker for oral cancer (Li et al, 1992;Xia et al, 1997;Werkmeister et al, 1999;Fong et al, 2008) and also as a prognostic marker (Pinto et al, 2010;Stoicanescu et al, 2013) for monitoring disease progression. However, there is also evidence stating that low/absence of HER2/neu expression in oral cancer (Khan et al, 2002;Schartinger et al, 2004;Henning Hanken et al, 2014). Henning et al demonstrated that Her2 protein and gene amplification was only detectable in a small subset of squamous cell carcinomas of the head and neck region as well as oral squamous cell carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Salivary Her2/neu Levels in Differentiation of Oral Premalignant Disorders and Oral Squamous Cell Carcinomas

Varun¹,

Dineshkumar²,

Jayant³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Oral squamous cell carcinoma (OSCC) is thought to develop from precancerous dysplastic lesions through multistep processes of carcinogenesis involving activation of oncogenes and loss of tumor suppressor genes. The human epidermal growth factor receptor 2 (Her-2/neu [erbB-2]), a cell membrane glycoprotein, is a growth factor receptor that has receptor tyrosine kinase activity. Her2/neu activation plays a central role in cell proliferation and survival. It has been shown that overexpression of Her2/neu increases the rate of cell division and growth, leading to precancerous changes. The aim of the present study was to compare the serum and salivary Her2/neu levels between cases with premalignant and malignant oral lesions. Materials and Methods: Fasting blood samples and unstimulated saliva by passive drooling were collected from three groups of healthy control (n=20), premalignant disorder (PMD) (n=20) and OSCC (n=25) subjects. The HER2 extracellular domain (HER2 ECD) levels were measured using ELISA. Results: The levels of serum Her2/neu showed no significant differences between any of the groups but on the other hand salivary Her2/neu levels were found to be significantly (p<0.05) higher when compared between control (median 68.7 pg/ml, range: 21.5 -75.8) and OSCC (median 145.6 pg/ml, range: 45.1-191.1). A similar trend was observed when comparing between PMD (median 43.3, range: 22.1 -94.7) and OSCC with a statistical significance of p<0.05. Conclusions: Our study provided evidence of increased salivary Her2/neu in OSCC when compared to PMD and control which was not the case for serum levels. This suggests that probably Her2/neu is not highly amplified as in breast cancer so as to be reflected in serum. Since saliva is in local vicinity of the OSCC, even a mild increase might be mirrored. On the whole, this study proposes Her2/neu as marker for distinguishing premalignant and malignant conditions.

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Section: Discussionmentioning

confidence: 99%

Salivary Her2/neu Levels in Differentiation of Oral Premalignant Disorders and Oral Squamous Cell Carcinomas

Varun¹,

Dineshkumar²,

Jayant³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…Anomalies in certain oncogenes such as ErbB1 (Her-1), ErbB2, and N-, K-and H-ras have not been found to play a key role in oral cancer (40)(41)(42)(43). When altered, genes that code for the synthesis of cyclin proteins, may act as oncogenes.…”

Section: 88 --------------------------------------------------------mentioning

confidence: 99%

Genetic and molecular alterations associated with oral squamous cell cancer (Review)

Pérez-Sayáns¹

2009

Oncol Rep

107

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Abstract. The development of oral squamous cell cancer (OSCC) is a multistep process involving the accumulation of multiple genetic alterations modulated by genetic predisposition and environmental influences such as tobacco and alcohol use, chronic inflammation, and viral infections. All of these factors can lead to a wide range of genetic and molecular alterations that can be detected using a range of molecular studies. The alterations mostly affect two large groups of genes: oncogenes and tumor suppressor genes, which can be either inactivated or overexpressed through mutations, loss of heterozygosity, deletions, or epigenetic modifications such as methylation. Other molecules that are closely associated with tumor pathogenesis and prognosis also exist and warrant further study. Important advances in molecular biology are helping to shed light on oral cancer and thus aiding in the early diagnosis and development of new personalized treatment approaches. The purpose of the review is to explore the genetic and molecular alterations associated with OSCC.

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“…One of the favourized targets is the epidermal growth factor receptor (EGFR), a type 1 tyrosine kinase membrane receptor that regulates important cellular functions in epithelial malignancies. EGFR has been found to be frequently overexpressed in head and neck squamous cell carcinomas [29,30]. Overexpression of EGFR has been correlated with worse patient survival in head and neck cancer, although results were not concordant between studies [29][30][31].…”

Section: Blocking Egfr: a New Perspectivementioning

confidence: 99%

Head and neck cancer: a step forward

Jelić¹,

Popov²,

Schartinger

et al. 2010

memo

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Head and neck cancers have for a long time been orphan cancers for any trials of individualized treatment, at least in part because the number of active cytotoxic drugs has been for a long time rather restricted. Histology did not infl uence treatment modality and the use of particular cytotoxic drugs. Undiff erentiated carcinoma of the nasopharynx was the fi rst tumour type to enhance investigations in individualized treatment, as regards to choice of cytotoxic drugs and combinations of chemo and radiotherapy. Recently the HPV16/18 positive carcinoma of the oropharynx has arisen as a topic for individualized approach. Th e biologicals are relatively late newcomers in the arsenal of drugs available for head and neck cancer. Th e same statement is related to research of possible targets and thus investigations of subpopulations that might benefi t from a particular drug or a particular pathway inhibition. Individualized drug treatment in head and neck cancer appears to be at its promising beginnings. The past decadesIn the last two decades, until recently, few advances have been made in the treatment of head and neck cancer, either in adjuvant, neoadjuvant, concomitant and palliative setting.Since meta-analyses showed a benefi t, concurrent chemoradiotherapy (CRT) widely replaced radiotherapy (RT) alone in the treatment of unresectable head and neck sqamous cell carcinoma (HNSCC) [1][2][3]. Th e principal cytostatic drugs have shown to be 5-fl ourouracil alone, cisplatin alone, mitomycin C alone, or 5-FU and cisplatin [4]. Amongst the platinum derivatives, cisplatin has been proven to be the drug of choice, more active in single drug setting than its analogue carboplatin and therefore the combination of cisplatin and continuously infusional 5-FU emerged as the treatment of choice [5,6]. Th e continuous infusional 5-FU-cisplatin regimen remained the standard, occasional although phase II trials appeared to demonstrate that the 4 h infusional 5-FU was as active as continuous infusional 5-FU when combined to cisplatin in both neoadjuvant and palliative setting [7]. Other cytostatic drugs like capecitabine in combination with paclitaxel or cisplatin are found to be well tolerated and eff ective but still fail to convince as a fi rst-line treatment in unresectable HNSCC [8,9]. Bleomycin and methotrexat in combination with radiation even showed to considerably enhance acute mucosal toxicity without any survival benefi t and therefore have been exluded from a large meta-analysis [1]. In the last decades the unconventional fractionated therapy has been studied extensively and showed that hyperfractionation leads to signifi cant improvement of overall survival, if used as a single modality. On the other hand accelerated radiotherapy alone is not that eff ective, especially in extreme treatments with decreased doses or split course radiation shedule [1,10]. Th e role of altered fractionated radiotherapy in the combined setting with chemotherapy is less conclusive and still under investigation.In adjuvant treatment CRT shoul...

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

Cited by 21 publications

References 18 publications

Salivary Her2/neu Levels in Differentiation of Oral Premalignant Disorders and Oral Squamous Cell Carcinomas

Salivary Her2/neu Levels in Differentiation of Oral Premalignant Disorders and Oral Squamous Cell Carcinomas

Genetic and molecular alterations associated with oral squamous cell cancer (Review)

Head and neck cancer: a step forward

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