Aberrant immunoexpression of p53 tumour-suppressor and Bcl-2 family proteins (Bcl-2 and Bax) in ameloblastomas and odontogenic keratocysts

Abstract

Background: The growth of ameloblastomas (odontogenic tumours) and odontogenic keratocyst (OKC) (developmental cyst) is associated with the expression of proteins related to cell survival and apoptosis. Bcl-2-associated protein X (Bax) and the tumour suppressor protein p53 collectively promote p53-mediated apoptosis. This study aimed to assess the immunohistochemical expression of p53, Bcl-2 and Bax in conventional ameloblastoma (CA), unicystic ameloblastoma (UA) types, and OKC sporadic (OKC-NS/S) and syndromic (OKC-NBSCC).

Material and methods: Paraffinized blocks of CA (n=18), UA (n=15), OKC-NS/S (n=18) and OKC-NBSCC (n=15) fixed in 10% formalin were used. After diagnosis, tissue specimens were stained by immunohistochemistry for p53, Bcl-2 and Bax marker. Stained cells were randomly counted in five high power fields. The data analysis was performed via Shapiro-Wilk test, ANOVA with Tukey's multiple comparisons or Kruskal-Wallis with Dunn's multiple comparisons. Statistical significance was defined as p<0.05.

Results: We did not observe differences between p53 expression in CA, mural UA (MUA), intraluminal/luminal UA (I/LUA), OKC-NS/S, and OKC-NBSCC (19.69%, 18.74%, 16.76%, 12.35% and 9.04%, respectively). Similar results were recognized for Bax expression in CA, MUA, I/LUA, OKC-NS/S, and OKC-NBSCC (33.72%, 34.95%, 22.94, 21.58% and 20.76%, respectively). However, we recognized significant differences between Bcl-2 expression in OKC-NS/S vs MUA, OKC-NS/S vs I/LUA, OKC-NS/S vs CA, OKC-NBSCC vs MUA, OKC-NBSCC vs I/LUA, and I/LUA vs CA. P53, Bcl-2 and Bax levels were higher in mural morphological areas versus intraluminal and luminal morphological areas in UA.

Conclusions: There is a tendency for an increased expression of p53, Bcl-2, and Bax proteins in CA, and mural proliferation of UA, compared to lesions with a cystic morphology, which could be associated with a local aggressive behaviour. Key words:p53, Bcl-2, Bax protein, apoptosis, odontogenic tumour, odontogenic cyst.

Figure 1

Immunohistochemical protein expression of p53 (400x). (A) conventonal ameloblastoma; (B) luminal unicystic UA; (C) intraluminal UA; (D) mural UA; (E), OKC non-syndromic or sporadic; (F), OKC related NBSCC; (G), EPC: oral squamous cell carcinoma; (H), ENC: oral squamous cell carcinoma. Abbreviations: UA: unicystic ameloblastoma; EPC: external positive control; ENC: external negative control; OKC: odontogenic keratocyst; NBSCC: naevoid basal cell carcinoma syndrome.

Figure 2

Immunohistochemical protein expression of Bcl-2 (400x). (A) conventional ameloblastoma; (B) luminal unicystic UA; (C) intraluminal UA; (D) mural UA; (E), OKC non-syndromic or sporadic; (F), OKC related NBSCC; (G), EPC: non-Hodgkin lymphoma; (H), ENC: non-Hodgkin lymphoma. Abbreviations: UA: unicystic ameloblastoma; EPC: external positive control; ENC: external negative control; OKC: odontogenic keratocyst; NBSCC: naevoid basal cell carcinoma syndrome.

Figure 3

Immunohistochemical protein expression of Bax (400x). (A) conventional ameloblastoma; (B) luminal unicystic UA; (C) intraluminal UA; (D) mural UA; (E), OKC non-syndromic or sporadic; (F), OKC related NBSCC; (G), EPC: amygdala; (H), ENC: amygdala. Abbreviations: UA: unicystic ameloblastoma; EPC: external positive control; ENC: external negative control; OKC: odontogenic keratocyst; NBSCC: naevoid basal cell carcinoma syndrome.