p63 is more sensitive and specific than 34βE12 to differentiate adenocarcinoma of prostate from cancer mimickers

Document Type: Original Article


1 Kidney Transplantation Complications Research Center, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Solid Tumor Treatment Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Objective(s): Prostate cancer is the world’s leading cause of cancer and the second cause of cancer-related death in men after lung cancer. Differentiation of prostate adenocarcinoma from benign prostate lesions and hyperplasia sometimes cannot be done on the basis of morphologic findings. Considering the fact that in the prostate adenocarcinoma there is no basal cell layer, basal cell markers can help to differentiate prostate adenocarcinoma from cancer mimickers.
Materials and Methods:We studied 98 prostate biopsy blocks (40 adenocarcinoma and 58 benign lesions) for basal cell marker expression.
Results: p63 and 34βE12 were negative in all prostate adenocarcinoma specimens, but all benign prostate hyperplasia and high grade intraepithelial neoplasia cases expressed them.
Conclusion: Basal cell markers can help to distinguish prostate adenocarcinoma from cancer mimickers.


1.Rosai J. Rosai and Ackermans surgical pathology, 11th ed. Edinburg: Mosby; 2012. P. 1295.

2.Wang W, Sun X, Epstein JI. Parthial atrophy on prostate needle biopsy cores: a morphologic and  immune histochemical study . AM J Surg Pathol 2008; 32:851-857.

3.Gown AM, Vogel AM. Monoclonal antibodies to human intermediate filament proteins: II. Distribution of filament proteins in normal human tissues. Am J Pathol 1984; 114:309-321.

4.Brawer MK, Peehl DM, Stamy TA, Bostwick DG. keratin immune reactivity in the being and neoplastic human prostate. Cancer Res 1985; 45: 3663-3667.

5.Hedrick L, Epstien JI. Use of keratin 903 as an adjunct in the diagnosis of prostate carcinoma. Am J Surg Pathol 1983; 13:350-353.

6.O'Malley FP, Grignon DJ, shum DT. Use fullness of immune peroxides staining with high – molecular – weight cytokeratin in the differential diagnosis of  small-acinar lesions of the prostate gland. Virchows Arch A Patathol Anat Histopathol 1995; 417:191-196.

7.Wogno KJ, Epstein JI. The utility of basal cell-specific anti cyto keratin antibody (34 beta E 12) in the diagnosis of prostate cancer: a review of 228 cases. Am J Surg Pathol 1995; 19:251-260.

8.Signoretti S, Waltregny D, Dilks J, Isaac B, Lin D, Garraway L, et al. P63 is a prostate basal cell marker and is required for prostate development. Am J Pathol 2000; 157:1769-1775.

9.Parsons GK, Gage WR, Nelson WG, De Marzo AM. P63 protein expression is rare in prostate adenocarcinoma:implications for cancer diagnosis and carcinogenesis. Urology 2001; 58:619-624.

10.Amin MB, Tamboli P,Varma M, Srigley JR. Postatrophic hyper plasia of the prostate gland: e detailed analysis of its morphology in needle biopsy specimens. Am J Surg Pathol 1999; 23:925-931.

11.Humphrey PA. Prostate pathology. Chicago: ASCP press; 2003.

12.Oppenheimer JR, Wills ML, Epstein JI. Partial atrophy in prostate needle cores: Another diagnostic pitfall for the surgical pathologist. Am J Surg Pathol 1998; 22:440-445.

13.Zhou M, Shah R, Shen R, Rubin MA. Basal cell cocktail(34 BE12+p63) improve the detection of prostate basal cells. Am J Surg Pathol 2003; 27:365-371.

14.Gaudin PB, Epstein JJ. Adenosis of the prostate. Histologic features in needle biopsy specimens. Am J Surg Pathol 1995; 19:737-747.

15.Bost wick DG, Srigley J, Grignon D, Maksem J, Humphrey P, van der Kwast TH, et al. Atypical adenomatous hyper plasia of the prostate: morphologic criteria for its distinction from well-differetiated carcinoma. Hum Pathol 1993; 24:819-832.

16.Varma M, Linden MD, Amin MB. Effect of formalin fixation and epitope retrieval thechniques on antibody 34betaE12 immunostaining of prostate tissues. Mod Pathol 1999; 12:472-478.

17.Jczkowski KA, Cheng L, Craeford BG, Bostwick DG. Steam heat with on EDTA boffer and protease digestion optimizes immune histochemical expression of basal cell-specific antikertin 34 beta E12 to discriminate cancer in prostatic epithelium. Mod Pathol 1999; 12:1-4.

18.Shah RB, Ming Z, Le Blanc M, Snyder M, Rubin MA. Comparison of the basal cell-specific, markers, 34BE12 and P63, in the diagnosis of prostate cancer.Am J Surg Pathol 2002; 26:1161-1168.

19.Multhaupt HA, Fessler JN, Warol MJ. Loss of high-molecular weight antigenicity in prostate tissue obtained by trans urethral resection. Arch Pathol Lab Med 2000; 124:1764-1770.

20.Yang XJ, Leck sell K, Gaudin P, Epstein JI. Rare expression of high molecular –weight cytokeratin in adenocarcinoma of the prostate gland: a study of 100 cases of metastatic and locally advanced prostate cancer.Am J Surg Pathol 1999; 23:147-152.

21.Shah IA, Schlageter MO, Stinett P, Lechago J.  Cytokeratin immunohistochemistry as a diagnostic tool for distinguishing malignant from benign epithelial lesions of the prostate. Mod Pathol 1991; 4:220-224.

22.lindeman N, Weinder N. Immuno histochemical profile of prostatic and urothelial carcinoma impact of heat-induced epitope retrieval and presentation of tumors with inter mediate features. Appl Immuno Histochem 1996; 4:264-275.

23.Oliai BR, Kahane H, Epstein JJ. Can basal cells be seen in adenocarcinoma of the prostate? an immunohistochemical  study using high molewlar weight cytokeratin (clone 34BE 12) antibody. Am J Surg Pathol 2002; 26:1151-1160.

24.Herawi M, Epstein JI. Immunohistochemical anti body cocktail staining (P63/HMWCK/AMACR) of ductal carcinoma and gleason pattern 4 cribiform and non cribiform acinar adenocarcinomas of the prostate.Am J Surg Pathol 2007; 31:889-894.

25.Beach R, Gown AM, De Peralta-Venturina MN. P504S immunohistochemical detection in 405 prostatic specimens including 376 18- gauge needle biopsies. Am J Surg Pathol 2002; 26:1588-1596.

 26.Browne TJ, Hirsch MS, Brodsky G, Welch WR, Loda MF, Rubin MA. Prospective evaluation of AMACR (P504S) and basal cell markers in the assesssment of routine prostate needle biopsy specimens. Hum Pathol 2004; 35:1462-1468.

27.Jiang Z, Woda BA, Rock KL, Xu Y, Savas L, Khan A, et al. P504S:a new molecular marker for detection of prostate carcinoma. Am J Surg Pathol 2001; 25:1397-1404.

28.Rubin MA, Zhou M, Dhanasekaran SM, Varambally S, Barrette TR, Sanda MG, et al. alpha-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. JAMA 2002; 287:1662-1670.

29.Furusato B, Tan SH, Young D, Dobi A, Sun C, Mohamed AA, et al. ERG oncoprotein expression in prostate cancer: clonal progression of ERG-positive tumor cells and potential for ERG-based stratification. Prostate Cancer Prostatic Dis 2010; 13:228-237.

30.Yaskiv O, Zhang X, Simmerman K, Daly T, He H, Falzarano S, et al. The utility of ERG/P63 double immunohistochemical staining in the diagnosis of limited cancer in prostate needle biopsies. Am J Surg Pathol 2010; 35:1062-1068.

31.Park K, Tomlin SA, Mudaliar KM, Chiu YL, Esgueva R, Mehra R, et al. Antibody-based detection of ERG rearangement-positive prostate cancer. Neoplasia 2010; 12:590-598.