Overexpression of the human homologue of<i>Drosophila patched</i>(<i>PTCH</i>) in skin tumours: specificity for basal cell carcinoma

Nagano,; Bito,; Kallassy,; Nakazawa,; Ichihashi,; Ueda,

doi:10.1046/j.1365-2133.1999.02664.x

Cited by 21 publications

(6 citation statements)

References 10 publications

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“…Such an antibody is described here. Previous work had demonstrated overexpression of PTCH transcripts in BCNS and sporadic BCCs using quantitative RT‐PCR and in situ hybridization8, 17, 18. Our data now indicate that the pattern of PTCH expression in BCC is similar to the distribution of PTCH transcripts.…”

Section: Discussionsupporting

confidence: 79%

“…Increased levels of PTCH transcripts have been reported in both familial and sporadic BCCs by several groups, using either in situ hybridization or quantitative RT‐PCR16, 17. The pattern of expression observed involves focal high levels of transcripts in both the outer palisading basal cell layer and in tumour epithelial nests, as well as in deep follicular BCCs, in comparison to both superficial BCC and normal covering skin17, 18. However, it is not known whether increased levels of transcription are mirrored by overexpression of the corresponding protein.…”

Section: Introductionmentioning

confidence: 99%

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Expression of the Sonic Hedgehog receptor ‘PATCHED’ in basal cell carcinomas and odontogenic keratocysts

et al. 2001

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Basal cell carcinoma (BCC) is a common invasive skin lesion in Caucasians. Odontogenic keratocysts (OKs) are developmental, non-inflammatory oral cysts. They can be sporadic and/or multiple and are locally destructive. Basal cell naevus syndrome (BCNS) comprises both multiple BCCs and multiple OKs, in addition to several other systemic manifestations. The genetic defect underlying this autosomal dominant syndrome is a germ line mutation in the Sonic Hedgehog receptor PATCHED (PTCH) gene. For this study, a rabbit anti-peptide PTCH antiserum was produced. Immunohistochemistry procedures were performed using PTCH antibody and commercially produced GLI-1 antibody (downstream member in the hedgehog pathway) to stain 11 BCNS-OKs, eight sporadic OKs, two BCNS-BCCs, and six sporadic BCCs. Most of these lesions had been previously screened for PTCH mutation. Most BCCs (n=7) demonstrated moderate staining, with the heaviest staining in the outer palisading cell layer, except a BCNS-BCC which had mutation proximal to the sequence used for production of immunogenic peptide; this demonstrated only weak staining. Although moderate to heavy staining with PTCH antibody was demonstrated in the epithelium of both types of OK (n=19), a quite different pattern of staining of the basal cell layer was observed in the two patient groups. In BCNS, OK staining was heaviest in basal epithelial layers. In contrast, staining in non-BCNS odontogenic keratocysts was exclusively located in the superficial epithelial layers. Up-regulation of PTCH and GLI-1 protein was demonstrated in both BCCs and OKs. The pattern of PTCH expression matched the PTCH transcript pattern previously reported in BCCs and appeared sufficiently characteristic in OKs to allow differentiation between syndromic and non-syndromic cysts.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Expression of the Sonic Hedgehog receptor ‘PATCHED’ in basal cell carcinomas and odontogenic keratocysts

et al. 2001

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“…The PTC gene 13,41 . Expression studies with in situ hybridization and RT-PCR have shown PTC overexpression in BCCs as compared with normal skin 32,41 . Previous studies have demonstrated that SMO is also overexpressed in BCC, whereas SHH is expressed in only some BCCs 21,40 .…”

Section: Discussionmentioning

confidence: 99%

PTC gene mutations and expression of SHH, PTC, SMO, and GLI-1 in odontogenic keratocysts

Ohki

Kumamoto

Ichinohasama

et al. 2004

International Journal of Oral and Maxillofacial Surgery

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“…Unfortunately, in the differentiation of BCC from trichoepithelioma, both may show increased target gene expression 20,24 , 39 . However, the level of target gene expression may help to differentiate between superficial BCC and actinic keratosis 74 and in assessing whether a hair follicle or BCC is present at an excision margin 75 …”

Section: How Does Molecular Analysis Impact On the Minimum Dataset Fomentioning

confidence: 99%

Basal cell carcinoma: a dermatopathological and molecular biological update

2003

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The ideal classification of basal cell carcinoma (BCC) should be able to identify subtypes which correlate with clinical behaviour and treatment requirements. Unfortunately, however, such a classification has yet to be defined. In the interim, the currently most favoured classification is one based predominantly on histological growth pattern. This classification contributes to the useful concept of low- and high-risk histological subtypes of BCC. The latter are characterized by an increased probability of subclinical extension and/or incomplete excision and/or aggressive local invasive behaviour and/or local recurrence. The Royal College of Pathologists has published a minimum dataset for the histopathological reporting of BCC and this has been written to be compatible with the British Association of Dermatologists' management guidelines. Growth patterns to be reported include nodular, superficial, infiltrative/morphoeic and micronodular types, together with differentiation when of severely atypical or malignant squamous type (basosquamous carcinoma). Deep and peripheral excision margins will be reported to be either involved or clear. The latter will include a comment of a clearance of less than 1 mm for close margins and a measured distance in whole millimetres for other excisions. Clinical assessment and histology remain the 'gold standard' for evaluating BCC and cancers in general. However, in the postgenomic era emphasis is changing from the gathering and archiving of genomic data to its analysis and use in guiding clinical practice. In this context, a current goal is to define cancer phenotype in terms of molecular abnormalities and use this as a new gold standard. One way to assess whether this goal is being achieved for BCC is to determine whether our knowledge of its molecular pathology has any relevance to the minimum dataset for histological reporting. Knowledge of BCC molecular pathology has been fuelled by the recent discovery that deregulation of the Hedgehog (Hh) signalling pathway, a key player in embryonic patterning, appears to be fundamental to tumour growth. But despite accrual of a large amount of data concerning Hh pathway molecular alterations in neoplasia, little is known about the functional consequences of these changes in BCC, how they lead to tumour development, or how they relate to non-Hh pathway alterations such as TP53 mutation. Recent work suggests that the cellular localization of beta-catenin gives a degree of credence to the growth pattern classification of BCC. Furthermore, it is possible that beta-catenin may have a pathogenetic role in the invasive behaviour of BCC. This review draws on current evidence to discuss these issues and assess whether they are relevant to the minimum dataset.

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Overexpression of the human homologue ofDrosophila patched(PTCH) in skin tumours: specificity for basal cell carcinoma

Cited by 21 publications

References 10 publications

Expression of the Sonic Hedgehog receptor ‘PATCHED’ in basal cell carcinomas and odontogenic keratocysts

Expression of the Sonic Hedgehog receptor ‘PATCHED’ in basal cell carcinomas and odontogenic keratocysts

PTC gene mutations and expression of SHH, PTC, SMO, and GLI-1 in odontogenic keratocysts

Basal cell carcinoma: a dermatopathological and molecular biological update

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