Collagen XVII/BP180 Protein Expression in Squamous Cell Carcinoma of the Skin Detected With Novel Monoclonal Antibodies in Archived Tissues Using Tissue Microarrays and Digital Microscopy

Stelkovics, Éva; Korom, Irma; Marczinovits, Ilona; Molnár, J.; Rásky, K; Rásó, Erzsébet; Ficsor, Levente; Molnár, Béla; Kopper, László; Krenács, Tibor

doi:10.1097/pai.0b013e318162f8aa

Cited by 31 publications

(44 citation statements)

References 33 publications

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“…In line with maturation, keratinocytes lose their collagen XVII expression, however, it can be detected as an early marker of malignant transformation in epidermal squamous cell carcinomas [26]. Apart from detecting collagen XVII in early in situ HNSCC, no significant difference in collagen XVII expression was noted in relation to any clinicopathological variable tested.…”

Section: Discussionmentioning

confidence: 91%

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Szentkúti

Dános

Brauswetter³

et al. 2014

Pathol. Oncol. Res.

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Head and neck squamous cell carcinomas (HNSC C) show diverse clinicopathological features and are mostly linked with poor outcome. In this study, we tested if the expression of tumor growth, cell cycle and basement membrane anchorage related biomarkers allow prognostic and clinicopathological stratification of HNSCC. Archived HNSCC samples from 226 patients included into tissue microarrays (TMA) were tested using immunohistochemistry. Histopathological evaluation and the analysis of immunostaining for EGFR, Ki67, p53, p16 ink4 and Collagen XVII proteins were carried out in digital whole slides. Statistical evaluation was carried out using Pearson's Chi-square test and Kaplan-Meier survival analysis. In the tested cohort, hypopharyngeal cancers had the least favorable, and glottic cancers had the most favorable prognosis. High Ki67 positive tumor cell fractions were associated with significantly worse prognosis and elevated rate of lymph node metastasis. Both Ki67 and EGFR expression correlated significantly with the tumor localization. Ki67 index was the highest in the hypopharyngeal region and it proved to be the lowest in the glottic region. EGFR expression was the highest in the oral cavity and the lowest in the glottic region. The survival rate of patients with p16 ink4

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Section: Discussionmentioning

confidence: 91%

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Szentkúti

Dános

Brauswetter³

et al. 2014

Pathol. Oncol. Res.

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“…Collagen XVII was widely expressed from very early stage in the majority of tumor cells in SCC of the skin, including the metastases [11].…”

Section: Discussionmentioning

confidence: 99%

“…The increased expression of p16 ink4 in these oropharyngeal carcinomas is relatively easy to detect and has been shown to be an excellent surrogate marker of biologically active HPV infection [3,9,10]. In this study, we systematically tested the expressions of p16 ink4 and some other published prognostic markers (Ki67, p53, EGFR) along with a recently discovered early marker of SCC: Collagen XVII/BP 180 (CollXVII) [11] in head and neck cancers of different anatomical regions using tissue microarrays (TMA) and immunohistochemistry. Our goal was to clarify the regional differences in the expression of potential biomarkers of SSC progression in the head and neck region, which may assist in understanding of the diverse behavior of these malignancies.…”

Section: Introductionmentioning

confidence: 99%

Differential Biomarker Expression in Head and Neck Cancer Correlates with Anatomical Localization

Tamás

Szentkúti

Erős

et al. 2011

Pathol. Oncol. Res.

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We tested the expression of known (p16(ink4), Ki67, p53, EGFR) and a new immunohistochemical (collagen XVII/BP180) biomarker in head and neck squamous cell carcinomas (SCC) of diverse anatomical localization. Tissue microarrays (TMA) of 124 SCC were created, immunostained, and analyzed following whole slide digitalization using the Pannoramic Scan and the TMA Module software (3DHISTECH Kft, Budapest, Hungary). Statistical analysis of scoring results was carried out using Pearson's chi-square test. We observed the significant elevation of p16(ink4) and Ki67 expression in supraglottic, tonsillar and tonsillo-lingual SCCs compared to those affecting the oral cavity, oropharynx without tonsils, larynx without supraglottis and the hypopharynx. This differential antigen expression may reflect the diverse route of embryologic differentiation followed by the affected regions except those of the tonsils and the supraglottis which show similar antigenic pattern but diverse developmental path. All the other biomarkers tested including p53, collagen XVII and EGFR were detected in the majority of cancers including high grade cases, but did not reveal any significant regional difference. Based on our results oropharyngeal squamous cell carcinomas may not be regarded as one entity. Concerning the oral cavity and the oropharynx, cancers affecting the tonsils (palatine and lingual) show significantly elevated p16(ink4) and Ki67 expression; so as the cancers of the supraglottis compared to the rest of larynx. Consequently, tonsillar and supraglottic cancers show similar biomarker profiles. Correlation of differential biomarker expression with diverse biological behavior in head and neck cancers need further investigations.

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“…Most research involving collagen XVII has focused on its role in healthy and diseased skin. Collagen XVII is a hemidesmosomal adhesion protein, whose expression in normal skin is limited to the basal keratinocytes, which are anchored to the basement membrane via collagen XVII [15]. However, it is overexpressed in squamous cell carcinoma (SCC) of the skin and in melanoma [15, 16].…”

Section: Introductionmentioning

confidence: 99%

In epithelial cancers, aberrant COL17A1 promoter methylation predicts its misexpression and increased invasion

et al. 2016

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BackgroundMetastasis is a leading cause of death among cancer patients. In the tumor microenvironment, altered levels of extracellular matrix proteins, such as collagens, can facilitate the first steps of cancer cell metastasis, including invasion into surrounding tissue and intravasation into the blood stream. However, the degree of misexpression of collagen genes in tumors remains understudied, even though this knowledge could greatly facilitate the development of cancer treatment options aimed at preventing metastasis.MethodsWe systematically evaluate the expression of all 44 collagen genes in breast cancer and assess whether their misexpression provides clinical prognostic significance. We use immunohistochemistry on 150 ductal breast cancers and 361 cervical cancers and study DNA methylation in various epithelial cancers.ResultsIn breast cancer, various tests show that COL4A1 and COL4A2 overexpression and COL17A1 (BP180, BPAG2) underexpression provide independent prognostic strength (HR = 1.25, 95% CI = 1.17–1.34, p = 3.03 × 10−10; HR = 1.18, 95% CI = 1.11–1.25, p = 8.11 × 10−10; HR = 0.86, 95% CI = 0.81–0.92, p = 4.57 × 10−6; respectively). Immunohistochemistry on ductal breast cancers confirmed that the COL17A1 protein product, collagen XVII, is underexpressed. This strongly correlates with advanced stage, increased invasion, and postmenopausal status. In contrast, immunohistochemistry on cervical tumors showed that collagen XVII is overexpressed in cervical cancer and this is associated with increased local dissemination. Interestingly, consistent with the opposed direction of misexpression in these cancers, the COL17A1 promoter is hypermethylated in breast cancer and hypomethylated in cervical cancer. We also find that the COL17A1 promoter is hypomethylated in head and neck squamous cell carcinoma, lung squamous cell carcinoma, and lung adenocarcinoma, in all of which collagen XVII overexpression has previously been shown.ConclusionsParadoxically, collagen XVII is underexpressed in breast cancer and overexpressed in cervical and other epithelial cancers. However, the COL17A1 promoter methylation status accurately predicts both the direction of misexpression and the increased invasive nature for five out of five epithelial cancers. This implies that aberrant epigenetic control is a key driver of COL17A1 gene misexpression and tumor cell invasion. These findings have significant clinical implications, suggesting that the COL17A1 promoter methylation status can be used to predict patient outcome. Moreover, epigenetic targeting of COL17A1 could represent a novel strategy to prevent metastasis in patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0290-6) contains supplementary material, which is available to authorized users.

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Collagen XVII/BP180 Protein Expression in Squamous Cell Carcinoma of the Skin Detected With Novel Monoclonal Antibodies in Archived Tissues Using Tissue Microarrays and Digital Microscopy

Cited by 31 publications

References 33 publications

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Differential Biomarker Expression in Head and Neck Cancer Correlates with Anatomical Localization

In epithelial cancers, aberrant COL17A1 promoter methylation predicts its misexpression and increased invasion

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