Immunohistochemical demonstration of p63 in DMBA‐induced hamster buccal pouch squamous cell carcinogenesis

Yk, Chen; Ss, Hsue; Lm, Lin

doi:10.1034/j.1601-0825.2003.02920.x

Cited by 27 publications

(29 citation statements)

References 40 publications

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“…Lo Muzio et al also demonstrated positive correlations between the histologic grade and ΔNp63 positive rate in head and neck carcinoma (49). Moreover, other studies found significant association between the ΔNp63 positive rate and the degree of differentiation in nasopharyngeal carcinoma, lung carcinoma, and epidermal carcinoma (23,24,50,51). These results suggested that ΔNp63 was closely associated with the cell maturation of cancer cells as well as normal stratified squamous epithelium and the positive staining might reflect the immaturity of the cancer cell lineage.…”

Section: Discussionmentioning

confidence: 62%

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Increased ΔNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma

et al. 2011

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Abstract. This study examined immunohistochemical expression of ΔNp63, a keratinocyte stem cell marker, in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) and then to elucidate usefulness of ΔNp63 as a marker for diagnosis and prognosis. One-hundred and twelve cases of OL and 81 cases of OSCC were analyzed by immunohistochemical staining for ΔNp63, Ki-67, and cytokeratin 14. These labeling indices (LIs) were calculated, and the association of these LIs with clinicopathologic characteristics in the OL and OSCC was evaluated. In the OL, these LIs increased significantly according to the severity of epithelial dysplasia (p<0.0001). ΔNp63-LI in the OL with malignant transformation was significantly higher than that in the OL without (49.3 vs. 34.2%; p<0.01). In the OSCC, the LIs increased significantly in association with the histologic grade (p<0.0001). A significant difference between the high and low ΔNp63-LI groups was found in the incidence of cervical lymph node and distant metastasis (p<0.05). The prognosis of the high ΔNp63-LI (mean value >73.8%) group is poorer than that of the low ΔNp63-LI (mean value ≤73.8%) group (p<0.05). These results suggested that increased ΔNp63 expression is involved in malignant transformation in epithelial dysplasia and poor prognosis in OSCC. Introductionp63 gene is a homolog of p53, it is located on chromosome 3q27-29 and encodes multiple isotypes with divergent abilities in a variety of organs (1-4). p63 has two different promoter domains that generate two protein isoforms, TAp63 and ΔNp63; each isoform yields three isotypes (α, β, γ) generated by alternative splicing of the p63 COOH terminus; and TAp63 includes an NH 2 -terminal transactivation domain, which is absent in ΔNp63 (1-4,6,7). TAp63 transactivates p53 target genes to induce apoptosis by inhibiting cell proliferation in response to exposure of cells to DNA-damaging agents such as ultraviolet irradiation. In contrast, ΔNp63 exerts dominant-negative activities against TAp63 and p53, and ΔNp63 is thus considered as an oncoprotein (1,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).Recent studies have shown that p63 is essential for craniofacial development during morphogenesis, because p63 -/-mice represented craniofacial abnormalities including hypoplasia of jaws and defects of the teeth, hair follicles, lachrymal glands, and salivary glands (1,15). Furthermore, p63 -/-mice showed lack of squamous stratification in the epidermis and oral epithelium, suggesting that p63 plays critical roles in the epithelial development. Pellegrini et al also demonstrated that p63 was expressed in keratinocyte stem cells and involved in the proliferation and maintenance of this cell population (16). Thus, p63 has been characterized as a marker of keratinocyte stem cells.In the tumorigenesis as well as morphogenesis, the existence of a stem-like cell population with a self-renewal potential, capacity of development into multiple lineages, extensive proliferation activity, and high migration capability in the tumor tissue was revealed. ...

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Section: Discussionmentioning

confidence: 62%

“…Recently, some studies have demonstrated that ΔNp63 is expressed more highly in certain tumor tissues (22)(23)(24)(25)(26)(27)(28). However, little is known about the expression of ΔNp63 in OL and OSCC.…”

Section: Introductionmentioning

confidence: 99%

Increased ΔNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma

et al. 2011

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“…The P1 promoter is located in the 5V untranslating region (UTR) upstream of a noncoding exon 1 [3] and leads isoforms showing the acidic N-terminal transactivation (TA) domain (TAp63) [4,9,14]. The P2 promoter (cryptic promoter) [16] is located within the 23-kilobase-spanning intron 3 [3] and encodes isoforms lacking the N-terminal transactivation domain (DNp63) [4,9,10,14].…”

Section: Introductionmentioning

confidence: 99%

p63 overexpression associates with poor prognosis in head and neck squamous cell carcinoma

et al. 2005

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“…Studies with murine model have revealed that p63 knockout-mice display profound defects in differentiation of tissues with stratified epithelium, including skin, oral cavity and esophagus. Moreover, these animals did not develop teeth, hair follicles and salivary, lachrymal and mammary glands (1). In human oral mucosa, p63 is chiefly restricted to basal and parabasal layers of the normal epithelium.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical expression of p63, epidermal growth factor receptor (EGFR) and notch-1 in radicular cysts, dentigerous cysts and keratocystic odontogenic tumors

et al. 2012

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The aim of this study was to assess the immunohistochemical expression of p63 protein, epidermal growth factor receptor (EGFR) and Notch-1 in the epithelial lining of radicular cysts (RC), dentigerous cysts (DC) and keratocystic odontogenic tumors (KOT). For this study, 35 RC, 22 DC and 17 KOT were used. The clinical and epidemiological data were collected from the patient charts filed in the Oral Pathology Laboratory, University of Ribeirão Preto, Brazil. Immunohistochemical reactions against the p63, EGFR and Notch-1 were performed in 3-µm-thick histological sections. The slides were evaluated according to the following criteria: negative: <5% of positive cells, low expression: 5-50% of positive cells, and high expression: >50% of positive cells. Moreover, the intensity of EGFR and Notch-1 expressions was also evaluated. Fisher's exact test and Spearman's correlation coefficients were used for statistical analysis, considering a significance level of 5%. Almost all cases demonstrated p63, EGFR and Notch-1 expressions. The p63 expression was significantly higher in KOT (p<0.001). Positive correlation between these immunomarkers was observed. These findings suggest the participation of p63, EGFR and Notch-1 in the development, maintenance and integrity of cystic odontogenic epithelial lining, favoring lesion persistence. The high expression of p63 in KOT suggests that it may be related to their more aggressive biological behavior and marked tendency to recurrence.

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Immunohistochemical demonstration of p63 in DMBA‐induced hamster buccal pouch squamous cell carcinogenesis

Cited by 27 publications

References 40 publications

Increased ΔNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma

Increased ΔNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma

p63 overexpression associates with poor prognosis in head and neck squamous cell carcinoma

Immunohistochemical expression of p63, epidermal growth factor receptor (EGFR) and notch-1 in radicular cysts, dentigerous cysts and keratocystic odontogenic tumors

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