Adult sudden cardiac death: audit of 5 years of non‐hypertensive, non‐ischaemic causes and autopsy reports

Abstract

We examined whether p63 expression could induce squamous metaplasia in adenocarcinoma. Given the lack of available EPD cell lines, we used adenocarcinoma cell lines, MCF7 (breast adenocarcinoma) and DLD-1 (colonic adenocarcinoma). p63 isoforms, DNp63a, TAp63a, DNp63c and TAp63c, were ectopically overexpressed in these cells by using adenovirus vectors. 2 DNp63a (a predominant isoform in keratinocytes) and DNp63c induced CK14 expression, whereas the TA isoforms did not show elevated CK14 expression ( Figure 5A,B). We also found that DNp63a suppressed the expression of CK7 ( Figure 5C), which is expressed by some glandular epithelia but not by squamous epithelia. In addition, neither CK5 nor CK1 were induced by p63 ( Figure 5A).The mechanism of squamous metaplasia is not well understood, but is likely to be related to abnormalities in the genes that control cellular characteristics. p63 has been found to play a critical role in squamous epithelia by initiating epithelial stratification. 1 Here, p63 was connected with histopathological features. Further, in vitro studies showed that DNp63a, the predominant isoform, induced CK14 expression in adenocarcinoma cells but suppressed CK7. Thus, p63 expression may be the cause rather than the consequence of squamous metaplasia.Although the occurrence of squamous metaplasia in adenocarcinoma is generally associated with a poor prognosis, 3 the association between p63 expression and enhanced malignancy is a matter of controversy. 1 Poor prognosis has been correlated with p63 up-regulation in some carcinomas, whereas it has also been associated with its down-regulation in others. 4,5 Much remains to be clarified about the function of p63.EO and RO contributed equally to this work. 1. Mills AA. p63: oncogene or tumor suppressor? Curr. Opin. Genet. Dev. 2006; 16; 38-44. 2. Okuyama R, Ogawa E, Nagoshi H et al. p53 homologue, p51 ⁄ p63, maintains the immaturity of keratinocyte stem cells by inhibiting Notch1 activity. Oncogene 2007; 26; 4478-4488. 3. Madura JA, Jarman BT, Doherty MG et al. Adenosquamous carcinoma of the pancreas. Arch. Surg. 1999; 134; 599-603. 4. Garcia S, Dales JP, Charafe-Jauffret E et al. Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype.