p63 short isoforms are found in invasive carcinomas only and not in benign breast conditions

Abstract

Two N-terminal isoforms characterize the p63 protein: the transactivating isoform TAp63 and the amino-terminal truncated isoform DeltaNp63. Two further N-terminal isoforms lacking exon 4 (d4TAp63 and DeltaNp73L) have been reported. Purpose of the study was to investigate the molecular expression of N-terminal p63 isoforms in benign and malignant breast tissues. Eighteen randomly selected cases of invasive breast carcinoma (IBC) of luminal type, two cases of in situ duct carcinoma (DCIS/DIN), and 20 specimens of normal and benign breast tissues were studied. All cases were immunostained for p63. Reverse polymerase chain reaction and nested PCR were performed to evaluate p63 N-terminal expression patterns. These isoforms whenever present were validated by sequencing. All cases of normal breast, benign lesions, and the two cases of DCIS/DIN expressed DeltaNp63 and TAp63 isoforms only. The two variants lacking exon 4 (DeltaNp73L and d4TAp63) were not found. All invasive carcinomas expressed the DeltaNp63 and TAp63 isoforms as well as the two short isoforms lacking exon 4 which were found in 11 (d4TAp63) and four (DeltaNp73L) cases. The present cases of luminal-type IBC showed p63 isoforms together with short variants lacking exon 4. These isoforms were not observed in non-neoplastic breast tissue. Presence of p63 in invasive breast carcinomas of luminal type, as seen at molecular level, suggests caution to include p63 as a marker of basal-like carcinomas.

Expression of p63 is the sole independent marker of aggressiveness in localised (stage I–II) Merkel cell carcinomas

“…Positive controls tested on breast tissues as previously reported, 9 for the primers of p63 isoforms, were available to verify if our primers were effective at amplifying the targeted isoforms of p63 when some were never detected (data not shown).…”

“…Eight different protein isoforms of p63 based on alternative splicing have been described. 9,10 The aim of the present study was to further evaluate in a large case series the immunohistochemical detection of p63 as a prognostic marker especially in low-stage (stage I-II) patients of Merkel cell carcinoma. Moreover, in all cases p63 expression by immunohistochemistry and molecular analysis of its variants were studied in parallel, to compare the two different procedures.…”

p63 Expression in Merkel Cell Carcinoma Predicts Poorer Survival yet May Have Limited Clinical Utility

“…p63 expression in cancer cells has been reported to be associated with worse prognosis in certain types of cancer including squamous cell carcinoma of the head and neck and a subset of B-cell lymphomas, but with better prognosis in other cancers including estrogen receptor-positive breast cancer 4-9 . The expression of p63 can be tested immunohistochemically and is a standard laboratory assay used in the diagnosis of prostate and breast cancers 10,11 .…”

Overexpression and ratio disruption of ΔNp63 and TAp63 isoform equilibrium in endometrial adenocarcinoma: correlation with obesity, menopause, and grade I/II tumors

“…In contrast, in only 0.6 % of patients with non-metaplastic invasive carcinoma, such an overexpression was observed, while in phyllodes tumors and sarcomas, p63 was not expressed at all (Koker and Kleer 2004). According to the study of De Biase et al, p63 was overexpressed in 55.5 % of basal-like breast carcinoma, while such expression in luminal-type invasive breast carcinoma was lower, from 0.6 to 19.5 % (de Biase et al 2010). TAp63 in particular was overexpressed in 75 % of samples.…”