COMBINED POSITIVITY FOR P63 AND ERG IN INTRADUCTAL CARCINOMA OF THE PROSTATE

• Published in: Anticancer research Vol. 38; no. 4; p. 2576
• Main Authors: Tognarelli, Alessio, Di Vico, Tommaso, Durante, Jacopo, Polito, Chiara, Meneghetti, Iacopo, Tesi, Lorenzo, Baldesi, Ramona, Faviana, Pinuccia, Bartoletti, Riccardo
• Format: Journal Article
• Language: English
• Published: Athens International Institute of Anticancer Research 01.04.2018
• Subjects: Basal cells; Biopsy; Bladder; Cancer; Cell proliferation; Diagnosis; Epithelial cells; ERG protein; Gene fusion; Health risks; Laparoscopy; Medical prognosis; p63 Protein; Patients; Preservation; Prognosis; Prostate cancer; Prostatectomy; Proteins; Radiation therapy; Risk; Robotic surgery; Serine; Survival; Tumors
• ISSN: 0250-7005; 1791-7530

Background/Aim: The term "intraductal carcinoma of the prostate" (IDC-P) was introduced almost 40 years ago and describes an expansive proliferation of malignant prostatic secretory epithelial cells within prostate ducts and acini, associated with at least partially preserved basal cell layer and significant architectural and cytological atypia. The presence of IDC-P in a pathological specimen is frequently associated with large tumour volume, advanced stage, high Gleason score, increased recurrence risk and poor prognosis, regardless of treatment status. ERG is a highly specific prostate cancer marker which is activated in more than 50% of prostate cancer cases, generally through a gene fusion with the androgen-responsive promoter of transmembrane protease serine 2.P63 protein has been regarded as a basal cell immunohistochemical marker. P63 is expressed in the proliferative layer of cells near the basement membrane where it likely prevents basal cells from differentiating and thereby helps to maintain their basal cell status. Immunohistochemical expression of both p63 and ERG protein is frequently found in patients with aggressive prostate cancer, despite the fact of expression of each independent marker in about 5% of patients with benign disease. The aim of the present study was to evaluate the potential impact of combined ERG and p63 expression in patients with aggressive high-risk prostate cancer. Materials and Methods: Pathological specimens from 69 patients who had previously undergone both radical retropubic prostatectomy and robotic assisted laparoscopic prostatectomy with bladder neck sparing (BNP) approach for medium-/high- risk prostate cancer between 2011 and 2015 have been selected to evaluate the prevalence of IDC-P. The criteria proposed by Guo and Epstein have been used for pathological analysis; according to these Authors, IDC-P is defined as malignant epithelial cells filling large acini and prostatic ducts, with preservation of basal cells forming either solid or dense cribriform patterns or loose cribriform or micropapillary patterns with either marked nuclear atypia (nuclear size 6× normal or larger) or comedonecrosis. Immunohistochemical staining for p63 and ERG was used to confirm retention of the basal layer and explore their potential role in diagnosis and in the long term disease prognosis. The mean age at time of prostatectomy was 67±6.9 years; tumor stage was pT2aN0 in 1 case, pT2aN1 in 1 case, pT2bN0 in 1 case, pT2cN0 in 16 cases, pT2cN1 in 3 cases, pT3aN0 in 19 cases, pT3aN1 in 3 cases, pT3bN0 in 7 cases, pT3bN1 in 18 cases. Gleason score was 6 in 7 cases, 7 in 43 cases, 8 in 11 cases, 9 in 8 cases. Positive surgical margins (PSM) were found in the 85.6% specimens. Mean follow-up was 4.6±1.6 years. All 69 patients received conformational adjuvant radiotherapy. Biochemical progression-free survival curve was constructed according to the KaplanMeier method. Results: IDC-P was found in 31 out 69 cases (44.9%), in whom the pathological diagnosis was immunohistochemically confirmed by the combined positivity for p63 and ERG expression. Biochemical recurrence was found in 51.6% in the IDC-P group and 36.8% in the other group respectively. No significant differences in cancer related survival were found between the two groups. Conclusion: The presence of intraductal carcinoma of the prostate should be evaluated and documented correctly in both radical prostatectomy and needle prostate biopsy and the clinical implications thereof should be taken into consideration during treatment and follow-up of prostate cancer. On prostatectomy histological sections, p63 and ERG immune stains combines the high sensitivity of p63 and the high specificity of ERG and may be potentially useful in the work-up of prostate biopsies for the early identification of IDC-P and high-risk prostate cancer patients, above all in cases where the total amount of prostatic tissue is insufficient for a correct final pathological diagnosis.