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Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the process

View Article: PubMed Central - PubMed

ABSTRACT

Squamous cell carcinoma (SCC) is the second most common cancer worldwide and accounts for approximately 30% of all keratinocyte cancers. The vast majority of cutaneous SCCs of the head and neck (cSCCHN) are readily curable with surgery and/or radiotherapy unless high-risk features are present. Perineural invasion (PNI) is recognized as one of these high-risk features. The molecular changes during clinical PNI in cSCCHN have not been previously investigated. In this study, we assessed the global gene expression differences between cSCCHN with or without incidental or clinical PNI. The results of the analysis showed signatures of gene expression representative of activation of p53 in tumors with PNI compared to tumors without, amongst other alterations. Immunohistochemical staining of p53 showed cSCCHN with clinical PNI to be more likely to exhibit a diffuse over-expression pattern, with no tumors showing normal p53 staining. DNA sequencing of cSCCHN samples with clinical PNI showed no difference in mutation number or position with samples without PNI, however a significant difference was observed in regulators of p53 degradation, stability and activity. Our results therefore suggest that cSCCHN with clinical PNI may be more likely to contain alterations in the p53 pathway, compared to cSCCHN without PNI.

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Immunohistochemical detection of p53 protein in cSCCHN with clinical PNI.Representative images of p53 staining. (a) A tumor with a negative pattern of p53 expression; no p53 expression is visualized in any of the tumor cells nuclei; (b) The same pattern shown at higher magnification; (c) A tumor with a focal pattern of p53 expression; strong p53 expression is evident, but within restricted areas of the tumor tissue; positively stained cells are typically immersed in a background of negative or weakly positively stained cellular nuclei; (d) The same pattern shown at a higher magnification; (e) A tumor displaying a diffuse pattern of p53 protein expression; very strong positive p53 expression scattered extensively throughout the tissue; (f) The same pattern shown at a higher magnification. Nuclear p53 is visualized in red. Scale: a, c, e: 500 μM, 40×; b, d, f: 50 μM, 400×.
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f3: Immunohistochemical detection of p53 protein in cSCCHN with clinical PNI.Representative images of p53 staining. (a) A tumor with a negative pattern of p53 expression; no p53 expression is visualized in any of the tumor cells nuclei; (b) The same pattern shown at higher magnification; (c) A tumor with a focal pattern of p53 expression; strong p53 expression is evident, but within restricted areas of the tumor tissue; positively stained cells are typically immersed in a background of negative or weakly positively stained cellular nuclei; (d) The same pattern shown at a higher magnification; (e) A tumor displaying a diffuse pattern of p53 protein expression; very strong positive p53 expression scattered extensively throughout the tissue; (f) The same pattern shown at a higher magnification. Nuclear p53 is visualized in red. Scale: a, c, e: 500 μM, 40×; b, d, f: 50 μM, 400×.

Mentions: To further investigate the role of p53 in PNI, we stained an independent cohort of 27 cSCCHN tumors with no PNI, 27 with incidental and 31 with clinical PNI for p53 by immunohistochemistry. Tumors were assessed for p53 staining using the criteria established by Nyiraneza and colleagues21 (representative images shown in Fig. 3). The analysis showed that cSCCHN with clinical PNI was significantly more likely to show a strongly positive “diffuse over-expression” pattern of p53 staining than cSCCHN without PNI (Table 1). No tumors with clinical PNI were found to show “normal” p53 staining (Table 1).


Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the process
Immunohistochemical detection of p53 protein in cSCCHN with clinical PNI.Representative images of p53 staining. (a) A tumor with a negative pattern of p53 expression; no p53 expression is visualized in any of the tumor cells nuclei; (b) The same pattern shown at higher magnification; (c) A tumor with a focal pattern of p53 expression; strong p53 expression is evident, but within restricted areas of the tumor tissue; positively stained cells are typically immersed in a background of negative or weakly positively stained cellular nuclei; (d) The same pattern shown at a higher magnification; (e) A tumor displaying a diffuse pattern of p53 protein expression; very strong positive p53 expression scattered extensively throughout the tissue; (f) The same pattern shown at a higher magnification. Nuclear p53 is visualized in red. Scale: a, c, e: 500 μM, 40×; b, d, f: 50 μM, 400×.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5035993&req=5

f3: Immunohistochemical detection of p53 protein in cSCCHN with clinical PNI.Representative images of p53 staining. (a) A tumor with a negative pattern of p53 expression; no p53 expression is visualized in any of the tumor cells nuclei; (b) The same pattern shown at higher magnification; (c) A tumor with a focal pattern of p53 expression; strong p53 expression is evident, but within restricted areas of the tumor tissue; positively stained cells are typically immersed in a background of negative or weakly positively stained cellular nuclei; (d) The same pattern shown at a higher magnification; (e) A tumor displaying a diffuse pattern of p53 protein expression; very strong positive p53 expression scattered extensively throughout the tissue; (f) The same pattern shown at a higher magnification. Nuclear p53 is visualized in red. Scale: a, c, e: 500 μM, 40×; b, d, f: 50 μM, 400×.
Mentions: To further investigate the role of p53 in PNI, we stained an independent cohort of 27 cSCCHN tumors with no PNI, 27 with incidental and 31 with clinical PNI for p53 by immunohistochemistry. Tumors were assessed for p53 staining using the criteria established by Nyiraneza and colleagues21 (representative images shown in Fig. 3). The analysis showed that cSCCHN with clinical PNI was significantly more likely to show a strongly positive “diffuse over-expression” pattern of p53 staining than cSCCHN without PNI (Table 1). No tumors with clinical PNI were found to show “normal” p53 staining (Table 1).

View Article: PubMed Central - PubMed

ABSTRACT

Squamous cell carcinoma (SCC) is the second most common cancer worldwide and accounts for approximately 30% of all keratinocyte cancers. The vast majority of cutaneous SCCs of the head and neck (cSCCHN) are readily curable with surgery and/or radiotherapy unless high-risk features are present. Perineural invasion (PNI) is recognized as one of these high-risk features. The molecular changes during clinical PNI in cSCCHN have not been previously investigated. In this study, we assessed the global gene expression differences between cSCCHN with or without incidental or clinical PNI. The results of the analysis showed signatures of gene expression representative of activation of p53 in tumors with PNI compared to tumors without, amongst other alterations. Immunohistochemical staining of p53 showed cSCCHN with clinical PNI to be more likely to exhibit a diffuse over-expression pattern, with no tumors showing normal p53 staining. DNA sequencing of cSCCHN samples with clinical PNI showed no difference in mutation number or position with samples without PNI, however a significant difference was observed in regulators of p53 degradation, stability and activity. Our results therefore suggest that cSCCHN with clinical PNI may be more likely to contain alterations in the p53 pathway, compared to cSCCHN without PNI.

No MeSH data available.


Related in: MedlinePlus