PATHOLOGY

Aberrant diffuse expression of p63 in adenocarcinoma of the prostate on needle biopsy and radical prostatectomy: report of 21 cases
Osunkoya AO, Hansel DE, Sun X, Netto GJ, Epstein JI
Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA
Am J Surg Pathol. 2008; 32: 461-7

• Aberrant diffuse expression of p63 in prostate carcinoma cells is a rare and poorly understood phenomenon. We studied 19 cases of prostate cancer with aberrant diffuse expression of p63 on needle biopsy and reviewed the subsequent radical prostatectomies in 6 cases. In 19/21 cases, 100% of the cancer nuclei stained intensely for p63, with 70% staining in the remaining 2 cases. Two additional radical prostatectomies with aberrant p63 staining with no needle biopsies available for review were also analyzed. On the hematoxylin and eosin-stained slides, 19/21 cases (90.5%) showed a distinctive morphology composed predominantly of glands, nests, and cords with atrophic cytoplasm, hyperchromatic nuclei, and visible nucleoli. Needle biopsy cases ranged from Gleason patterns 3 to 5 with tumor identified on one or more cores, ranging from a minute focus to 80% of the core. In all 8 radical prostatectomies p63 positive cancer was present, with in 2/8 cases both p63 positive cancer and usual p63 negative acinar prostate cancer. In all 8 cases, the tumors were organ confined with negative margins and there was no seminal vesicle involvement or lymph node metastasis. The presence of p63 positive atypical glands with an infiltrative pattern and perineural invasion on radical prostatectomy confirmed the needle biopsy diagnosis of carcinoma. Rarely, prostate cancer can aberrantly express diffuse p63 staining in a nonbasal cell distribution leading to the erroneous diagnosis of atrophy or atypical basal cell proliferation. The diagnosis of prostate cancer is based on the morphology and confirmed by the absence of high molecular weight cytokeratin staining and positivity for alpha-methylacyl-CoA racemase in the atypical glands. Pathologists need to be aware of this rare and unusual phenomenon, which is a potential pitfall in prostate cancer diagnosis.
  
  
• Editorial Comment
  Pathologists use immunohistochemistry for the differential diagnosis between adenocarcinoma of the prostate and benign mimickers in difficult cases. The aim is to detect basal cells which excludes adenocarcinoma (1). The most frequently used markers for basal cells is clone 34ßE12 (a pool of high-molecular-cytokeratins 1,5,10,11 and 14) and p63. 34ßE12 stains the cytoplasm and p63 stains the nucleus of basal cells.
  The cases of adenocarcinoma with aberrant expression of p63 studied by Osunkoya et al. is a very important finding. Pathologists need to be aware of this rare and unusual phenomenon, which is a potential pitfall in prostate cancer diagnosis.

Reference
1. O’Malley FP, Grignon DJ, Shum DT: Usefulness of immunoperoxidase staining with high-molecular-weight cytokeratin in the differential diagnosis of small-acinar lesions of the prostate gland. Virchows Arch A Pathol Anat Histopathol. 1990; 417: 191-6.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil
E-mail: athanase@fcm.unicamp.br