Overexpression of EGFR and absence of C‐KIT expression correlate with poor prognosis in salivary gland carcinomas

Ettl, Tobias; Schwarz, Stephan; Kleinsasser, Norbert; Hartmann, Arndt; Reichert, T; Driemel, Oliver

doi:10.1111/j.1365-2559.2008.03159.x

Cited by 97 publications

(86 citation statements)

References 41 publications

(57 reference statements)

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“…This category contains KIT (targeted by imatinib and axinitib), 123-128 angiogenesis related growth factor receptors (VEGF, VEGF-R, PDGF and bFGF -targeted by axinitib), 129-131 human epidermal growth factor receptors (EGFR aka HER-1 or ErbB-1 and its ligands Amphiregulin and TGF-α -targeted by antibodies such as cetuximab and lowmolecular weight tyrosine kinase inhibitors such as gefinitib; 132 HER-2 or ErbB-2 -targeted by antibodies such as trastuzumab and lowmolecular weight tyrosine kinase inhibitors such as lapatinib, 122,132-136 HER-3 or ErbB-3; HER-4 or ErbB-4) [137][138][139][140][141] and Insulin-like growth factor IGF-1R. [142][143][144] The second class of markers are cell cycle oncogenes that are activated by the above mentioned growth factor-growth factor receptor interaction. These are SOX-4, NFκB, Kras, PI3K/Akt, Src, STAT3, mTOR, c-myc, and are less well studied in salivary gland cancer.…”

Section: Molecular Biology Advancesmentioning

confidence: 99%

“…Of explored targeted therapies so far, none has been shown to improve the result in this patient group, but a lot of effort continues to go in this direction. 121,[123][124][125][126][127][128][129][130][137][138][139][140][141][142][143][144][145] Outcomes and prognosis Treatment results in major treatment centers are displayed in Table 2. These numbers have to be appreciated in their specific context of stage, percentage high grade, treatment period and corresponding treatment regimens, patient inclusion criteria, and adequacy of follow-up.…”

Section: Radiotherapy and Chemotherapy In Unresectable Diseasementioning

confidence: 99%

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Parotid carcinoma: Current diagnostic workup and treatment

Poorten

Marchal²,

Nuyts

et al. 2010

Indian J Surg Oncol

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In this review we present recent progress in diagnostic workup, prognostic evaluation, treatment options and resulting outcomes. Whenever possible, complete resection remains the mainstay of treatment. Sacrifice of facial nerve branches is reserved for the clinically or electromyographically dysfunctioning facial nerve. Clinical or radiological neck disease demands combined surgery and radiotherapy. Treatment of the N0 neck is indicated for advanced stage-high grade tumors but the question remains unanswered whether this should be surgical or radiotherapeutic elective treatment. Surgery alone will cure low stage, low grade tumors, that show no additional negative prognostic factors following adequate resection. In all other tumors postoperative radiotherapy will improve locoregional control. This approach results in good locoregional control, in a way that distant metastasis remains the typical presentation of treatment failure. In this setting, the results of systemic treatment today remain limited, but a huge effort in the molecular biology field has been done to introduce targeted therapy into this domain of head and neck cancer. Disease control remains variable within the patient population. This variation can increasingly be predicted by systems that incorporate the combined information of multivariately identified and quantified prognostic factors into an individualized prognosis for the parotid carcinoma patient.

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Section: Molecular Biology Advancesmentioning

confidence: 99%

Section: Radiotherapy and Chemotherapy In Unresectable Diseasementioning

confidence: 99%

Parotid carcinoma: Current diagnostic workup and treatment

Poorten

Marchal²,

Nuyts

et al. 2010

Indian J Surg Oncol

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“…HeLa cells also express EGFR (25). EGFR has been proposed as a major target for cancer treatment because it is overexpressed in a variety of epithelial tumors (10,11). The phosphorylated EGFR generated downstream signal and activates the transcription factor AP-1 (26,27).…”

Section: Discussionmentioning

confidence: 99%

“…The expression of the angiogenesis-related factors in the salivary gland tumor may be a result of the interaction between tumor cells and the interstitial tissue that expresses many growth factors. Because of the expression of EGF receptors (EGFR) in many kinds of tumors (10,11), the abundant EGF may give a chance to tumor growth in the normal salivary gland. The expression of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and FGF-2 are induced by the activation of EGFR (12).…”

Section: Introductionmentioning

confidence: 99%

Recapitulating orthotopic tumor model through establishment of a parotid gland tumor with lung metastasis using HeLa cell injection into nude mice

Park

Kim²,

Choi³

et al. 2010

Oncol Rep

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Abstract.The interaction between tumor cells and surrounding normal cells is very important in the prognosis of tumors. The object of this study was to determine the effect of recipient bed of tumor xenograft on tumor metastasis using a novel parotid gland tumor model. HeLa cells were xenografted into the parotid gland or subcutaneous tissues of athymic mice. Eight weeks after the transplantation, all mice were euthanized and specimens were immunostained with antibodies for angiogenic factors. FGF-2 was given to HeLa cells and the effect on the cellular migration was determined. EGF was also given to HeLa cells for the evaluation of FGF-2 induction. Immunohistochemical staining was done for the vascular metastasis-related factors on 26 human salivary gland tumors. HeLa cells showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. Immunohistochemical staining revealed overexpression of FGF-2 in the parotid tumors compared to the subcutaneous tumors. The application of FGF-2 to implanting HeLa cells increased the cellular invasion in a dose-dependent manner. The application of EGF increases FGF-2 expression in HeLa cells. In clinical specimens, EGF and VEGF signaling proteins were more expressed than in normal salivary glandular tissues. In conclusion, a parotid tumor model of HeLa cells was successfully developed and it closely mimics high metastasis. These results indicate that recipient bed with intense EGF expression increases tumor metastasis through upregulation of FGF-2 expression.

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“…For salivary malignancies in general and not only applicable to ADCCs, a relatively recent study suggests that absence of C-kit expression but overexpression of EGFR correlated with poor prognosis [ 60 ]. In a study of 35 adenoid cystic carcinomas, the expression of galectin -3 , a betagalactoside-binding lectin implicated in tumour progression and metastasis, was investigated.…”

Section: Predictive Factors Treatment and Prognosismentioning

confidence: 99%