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OTX1 and OTX2 as Possible Molecular Markers of Sinonasal Carcinomas and Olfactory Neuroblastomas

View Article: PubMed Central - PubMed

ABSTRACT

OTX Homeobox genes are involved in embryonic morphogenesis and in the development of olfactory epithelium in adult. Mutations occurring in the OTX genes are reported to be associated to tumorigenisis in human. No reports correlate the expression of OTX genes and neoplasms of the nasal cavity. Thus, through immunohistochemical and Real-time PCR analysis we investigated OTX1 and OTX2 expression in the more frequent types of nasal and sinonasal tumours. Variable expression of both genes were found in normal sinonasal mucosa and in tumours. Interestingly, no expression of both OTX genes were detected in sinonasal intestinal-type adenocarcinomas; only OTX1 was found in non-intestinal-type adenocarcinomas and OTX2 was selectively expressed in olfactory neuroblastomas. In conclusion, OTX1 and OTX2 genes might have a role in the pathogenesis of different types of sinonasal neoplasms.

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Molecular expression of OTX1 (A) and OTX2 (B) genes in normal and neoplastic nasal tissues. Normal mucosae (control) (5 analysed cases), non-intestinal-type adenocarcinomas (NITAC) (5 analysed cases), intestinal-type adenocarcinomas (ITAC) (9 analysed cases), olfactory neuroblastomas (ON) (6 analysed cases), poorly differentiated neuroendocrine carcinomas (PDNEC) (8 analysed cases). The X axis indicates the type of tumour, while the Y axis represents the 2^-ΔCt values. The asterisk indicates data statistically significant (P<0.05) between control and tumours obtained by Student’s t-test.
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fig002: Molecular expression of OTX1 (A) and OTX2 (B) genes in normal and neoplastic nasal tissues. Normal mucosae (control) (5 analysed cases), non-intestinal-type adenocarcinomas (NITAC) (5 analysed cases), intestinal-type adenocarcinomas (ITAC) (9 analysed cases), olfactory neuroblastomas (ON) (6 analysed cases), poorly differentiated neuroendocrine carcinomas (PDNEC) (8 analysed cases). The X axis indicates the type of tumour, while the Y axis represents the 2^-ΔCt values. The asterisk indicates data statistically significant (P<0.05) between control and tumours obtained by Student’s t-test.

Mentions: Here, we reported only preliminary data statistically significant. In normal mucosae, immunohistochemistry showed strong and homogeneous nuclear immunoreactivity for OTX both in the ciliated pseudostratified respiratory-type epithelium and in the underlying submucosal glandular cells (Figure 1A); at the same time, Real-time PCR analysis demonstrated the expression of both OTX genes (Figure 2 A,B). Different immunoreactivity and molecular expression of OTX were found in all cases of the different types of analysed tumours (data not showed). Of particular interest were results obtained comparing ITAC and NITAC and ON and PDNEC tumours. Homogeneously distributed nuclear OTX expression was present in all NITACs (Figure 1B), whereas no immunoreactivity or immunoreactivity restricted to very few scattered cells was observed in ITAC cases (Figure 1C). In fact, OTX1 gene was expressed in all NITACs but it was completely absent in ITACs (Figure 2A). No OTX2 expression was observed both in all ITACs and in all NITACs (Figure 2B). Contrarily, intense OTX immunoreactivity was present in all ONs (Figure 1D); in all these tumours OTX1 gene was completely absent (Figure 2A) whereas OTX2 was over-expressed (Figure 2B). Among PDNECs OTX expression varied in intensity and percentage of positive cells (Figure 1E). Also the expression of both the OTX genes varied in PDNECs. Immuno - histochemical statistical analysis demonstrated that OTX immunoreactivity was significantly absent in ITAC compared to all the tumour types (P<0.001). As regards the OTX genes expression, Student’s t-test confirmed data statistically significant (*) (P<0.05) for OTX1 in controls vs ITACs, controls vs ONs, controls vs PDNECs and for OTX2 in controls vs NITACs, controls vs ITACs, controls vs ONs, controls vs PDNECs.


OTX1 and OTX2 as Possible Molecular Markers of Sinonasal Carcinomas and Olfactory Neuroblastomas
Molecular expression of OTX1 (A) and OTX2 (B) genes in normal and neoplastic nasal tissues. Normal mucosae (control) (5 analysed cases), non-intestinal-type adenocarcinomas (NITAC) (5 analysed cases), intestinal-type adenocarcinomas (ITAC) (9 analysed cases), olfactory neuroblastomas (ON) (6 analysed cases), poorly differentiated neuroendocrine carcinomas (PDNEC) (8 analysed cases). The X axis indicates the type of tumour, while the Y axis represents the 2^-ΔCt values. The asterisk indicates data statistically significant (P<0.05) between control and tumours obtained by Student’s t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5304267&req=5

fig002: Molecular expression of OTX1 (A) and OTX2 (B) genes in normal and neoplastic nasal tissues. Normal mucosae (control) (5 analysed cases), non-intestinal-type adenocarcinomas (NITAC) (5 analysed cases), intestinal-type adenocarcinomas (ITAC) (9 analysed cases), olfactory neuroblastomas (ON) (6 analysed cases), poorly differentiated neuroendocrine carcinomas (PDNEC) (8 analysed cases). The X axis indicates the type of tumour, while the Y axis represents the 2^-ΔCt values. The asterisk indicates data statistically significant (P<0.05) between control and tumours obtained by Student’s t-test.
Mentions: Here, we reported only preliminary data statistically significant. In normal mucosae, immunohistochemistry showed strong and homogeneous nuclear immunoreactivity for OTX both in the ciliated pseudostratified respiratory-type epithelium and in the underlying submucosal glandular cells (Figure 1A); at the same time, Real-time PCR analysis demonstrated the expression of both OTX genes (Figure 2 A,B). Different immunoreactivity and molecular expression of OTX were found in all cases of the different types of analysed tumours (data not showed). Of particular interest were results obtained comparing ITAC and NITAC and ON and PDNEC tumours. Homogeneously distributed nuclear OTX expression was present in all NITACs (Figure 1B), whereas no immunoreactivity or immunoreactivity restricted to very few scattered cells was observed in ITAC cases (Figure 1C). In fact, OTX1 gene was expressed in all NITACs but it was completely absent in ITACs (Figure 2A). No OTX2 expression was observed both in all ITACs and in all NITACs (Figure 2B). Contrarily, intense OTX immunoreactivity was present in all ONs (Figure 1D); in all these tumours OTX1 gene was completely absent (Figure 2A) whereas OTX2 was over-expressed (Figure 2B). Among PDNECs OTX expression varied in intensity and percentage of positive cells (Figure 1E). Also the expression of both the OTX genes varied in PDNECs. Immuno - histochemical statistical analysis demonstrated that OTX immunoreactivity was significantly absent in ITAC compared to all the tumour types (P<0.001). As regards the OTX genes expression, Student’s t-test confirmed data statistically significant (*) (P<0.05) for OTX1 in controls vs ITACs, controls vs ONs, controls vs PDNECs and for OTX2 in controls vs NITACs, controls vs ITACs, controls vs ONs, controls vs PDNECs.

View Article: PubMed Central - PubMed

ABSTRACT

OTX Homeobox genes are involved in embryonic morphogenesis and in the development of olfactory epithelium in adult. Mutations occurring in the OTX genes are reported to be associated to tumorigenisis in human. No reports correlate the expression of OTX genes and neoplasms of the nasal cavity. Thus, through immunohistochemical and Real-time PCR analysis we investigated OTX1 and OTX2 expression in the more frequent types of nasal and sinonasal tumours. Variable expression of both genes were found in normal sinonasal mucosa and in tumours. Interestingly, no expression of both OTX genes were detected in sinonasal intestinal-type adenocarcinomas; only OTX1 was found in non-intestinal-type adenocarcinomas and OTX2 was selectively expressed in olfactory neuroblastomas. In conclusion, OTX1 and OTX2 genes might have a role in the pathogenesis of different types of sinonasal neoplasms.

No MeSH data available.


Related in: MedlinePlus