Expression of the Sonic hedgehog pathway in squamous cell carcinoma of the skin and the mucosa of the head and neck

Schneider, Sven; Thurnher, Dietmar; Kloimstein, Philipp; Leitner, Verena; Petzelbauer, Peter; Pammer, Johannes; Brunner, Markus; Erovic, Boban M.

doi:10.1002/hed.21437

Cited by 49 publications

(50 citation statements)

References 31 publications

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“…Schneider et al [22] failed to note any expression of SHH signaling proteins in oral normal mucosa. However, in our study, low levels of GLI-1 were expressed in NNT1.…”

Section: Discussionmentioning

confidence: 98%

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Activation of sonic hedgehog signaling in oral squamous cell carcinomas: a preliminary study

et al. 2011

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Sonic hedgehog signaling is important for human development, and aberrant regulation of this pathway can result in the development of tumors. The aim of this study was to examine the expression of sonic hedgehog signaling molecules in oral squamous cell carcinoma. By quantitative real-time polymerase chain reaction, the expression of SHH, SMO, PTCH-1, and GLI-1 was analyzed in 30 oral squamous cell carcinoma cases and 8 samples of nonneoplastic oral mucosa and associated to clinical pathologic features. The expression of β-catenin, cyclin D1, Wnt-1, and Egfr was evaluated by immunohistochemistry in 26 available cases of oral squamous cell carcinoma. Normal oral mucosa from healthy individuals was negative for all genes that were evaluated. SHH, PTCH-1, SMO, and GLI-1 were not expressed in nonneoplastic oral mucosa, and low levels of GLI-1 were observed in nonneoplastic oral mucosa that was adjacent to the tumor. All oral squamous cell carcinoma cases expressed high levels of PTCH-1, SMO, and GLI-1 and were devoid of SHH. The expression of SMO was associated with clinical stage (P = .022) and a borderline association in cervical lymph node metastasis (P = .053). PTCH-1 expression showed a strong correlation with SMO (rs = 0.64; P < .001) and GL-1 (rs = 0.70; P < .001); SMO and GLI-1 also correlated with each other (rs, 0.55; P < .001). All proteins evaluated were expressed as cyclin D1 (92% of samples), β-catenin (73%), Egfr (46%), or Wnt-1 (32%). Our data demonstrate that sonic hedgehog signaling is activated in oral squamous cell carcinoma and suggest that this pathway mediates its tumorigenesis.

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“…Schneider et al [22] failed to note any expression of SHH signaling proteins in oral normal mucosa. However, in our study, low levels of GLI-1 were expressed in NNT1.…”

Section: Discussionmentioning

confidence: 98%

“…Schneider et al [22] assessed the expression of SHH signaling proteins in head and neck squamous cell carcinomas. Here, we found the transcriptional levels of genes in the SHH pathway in human OSCC.…”

Section: Discussionmentioning

confidence: 99%

Activation of sonic hedgehog signaling in oral squamous cell carcinomas: a preliminary study

et al. 2011

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“…Previous studies have shown an important role of the Hh signaling pathway in the development of a variety of solid tumors and have revealed its impact on the outcome of most incurable aggressive malignancies [Watkins et al 2003;Liao et al 2009;Watkins and Peacock, 2004;Datta and Datta, 2006;Brunner et al 2010;Schneider et al 2011;Vestergaard et al 2006]. The Hh signaling pathway plays a crucial role in tumorigenesis when reactivated in adult tissues through sporadic mutations and other mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Sonic hedgehog pathway expression in non-small cell lung cancer

et al. 2012

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Abstract:Objective: Activation of the hedgehog pathway is an important signaling mechanism crucial in embryogenesis and has strong links to carcinogenesis. This study investigates the expression of the Sonic hedgehog pathway molecules in non-small cell lung tumors as it relates to clinical outcome of various non-small cell lung cancers. Methods: A tissue microarray with 81 samples from 42 patients with various non-small cell lung cancer histologies was examined without the aid of laser microdissection. All samples were stained with antibodies directed against Sonic hedgehog, Ptch-1, Smoothened, and Gli-1. Results: Most of the tumor samples showed negative to weak expression of the pathway proteins (Sonic hedgehog, 38% negative to 20% weak; Ptch-1, 100% negative; Smoothened, 69% negative to 7% weak; Gli-1, 57% negative to 5% weak) compared with higher expression in normal lung epithelial cells. Conclusion:The same pathway expression did not correlate with clinical outcome. While our results do not provide any indication that the pathway molecules are correlated to overall patient survival possibly due to the limited sample size, our study shows minimum overexpression of Sonic hedgehog pathway in non-small cell lung cancer and this did not correlate clinically with patient outcome.

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“…Recently, Schneider et al [28] published data on the expression of the HH pathway in squamous cell carcinomas of the skin in comparison to HNSCC; however, they used only semiquantitative methods for analysis and found heterogeneous expression rates in these tumour entities. Wang et al [29] only considered SHH, PTCH, and Gli1 expression in oral squamous cell carcinomas from 40 patients, but found that PTCH overexpression was associated with lymphatic spread and that Gli1 overexpression was correlated with primary tumour size, lymphatic metastasis and tumour recurrence (fig.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of the Hedgehog Signalling Pathway in Head and Neck Squamous Cell Carcinoma

Dimitrova

Stöhr²,

Dehghani³

et al. 2013

Oncol Res Treat

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Background: Overexpression of the Hedgehog (HH) signalling pathway has been described in several malignancies and is associated with a poor prognosis. HH signalling blockade reduces tumour growth in vitro and in vivo. We aimed to determine whether head and neck squamous cell carcinomas (HNSCCs) express HH proteins in comparison to healthy mucosa. Patients and Methods: Formalin-fixed and paraffin-embedded tissue sections of 10 patients with HNSCC were stained with fluorescence-labelled antibodies for cytokeratin and HH proteins (SHH, PTCH1/2, SMO, Gli1-3) and photographs were taken with a laser scanning microscope. The pixel count and colour intensity were analysed in RGB (red/green/blue) colour mode, and expression levels were compared to healthy mucosa. Results: Image analysis in RGB mode provided objective evidence for the over-expression of HH signalling components in HNSCC, particularly with regard to the transcription factors Gli1 (10-fold) and SHH (5-fold) in comparison with healthy mucosa. The lowest levels were found for Gli3 in HNSCC. Conclusions: We postulate pivotal roles of Gli1 and SHH expression in the carcinogenesis of HNSCC. HH pathway overexpression appears to be involved in the initiation of tumour growth and spread due to its stem cell-modulating properties. Detection of HH pathway components, and especially Gli1 and SHH, in HNSCC might offer a promising target for further anticancer research in HNSCC.

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Expression of the Sonic hedgehog pathway in squamous cell carcinoma of the skin and the mucosa of the head and neck

Abstract: Hedgehog signaling is differentially regulated in squamous cell carcinomas of the skin and the head and neck. Sonic hedgehog expression may serve as a prognostic factor in patients with head and neck cancer.

Cited by 49 publications

References 31 publications

Activation of sonic hedgehog signaling in oral squamous cell carcinomas: a preliminary study

Activation of sonic hedgehog signaling in oral squamous cell carcinomas: a preliminary study

Sonic hedgehog pathway expression in non-small cell lung cancer

Overexpression of the Hedgehog Signalling Pathway in Head and Neck Squamous Cell Carcinoma

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