Prostate gland & seminal vesicles

IHC overview

Editorial Board Member: Maria Tretiakova, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Brian Ma, M.D.
Guang-Qian Xiao, M.D., Ph.D.

Last author update: 23 October 2020
Last staff update: 9 June 2023

Copyright: 2003-2024,, Inc.

PubMed Search: prostate[title] immunohistochemistry[title] pathology

Brian Ma, M.D.
Guang-Qian Xiao, M.D., Ph.D.
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Cite this page: Ma B, Xiao GQ. IHC overview. website. Accessed April 14th, 2024.
Definition / general
  • Diagnostic biomarker study of prostate tissue is one of the most common applications of immunohistochemistry in surgical pathology, especially for prostate needle biopsies (Mod Pathol 2018;31:S12)
  • In an appropriate histomorphologic setting, immunohistochemistry is very helpful in distinguishing between prostatic adenocarcinoma and its benign mimickers (Adv Anat Pathol 2018;25:387)
Essential features
  • Most used immunohistochemical stains include basal cell markers and prostate specific markers (Mod Pathol 2018;31:S12)
  • Hallmark of prostatic adenocarcinoma is the loss of basal cells; however, not all prostate glands without basal cells are carcinoma (Mod Pathol 2018;31:S12)
  • Triple antibody cocktail (also called PIN4 or PIN cocktail): mixture of p63, 34 beta E12 and AMACR / P504s
  • Survival and growth of normal and prostate cancer cells relying on the constitutive expression of AR and its signaling (Front Oncol 2019;9:858)
  • Prostate cancer often with increased fatty acid metabolites by overexpression of AMACR (J Cancer Res Ther 2017;13:21)
  • Overexpression of ERG from TMP-RSS2:ERG gene rearrangement playing an important role in the initiation of almost half of prostate cancer (Oncogene 2016;35:403)
Uses by pathologists
  • Diagnosis of primary invasive prostatic adenocarcinoma, mainly in the following settings:
    • Small focus of atypical glands / atypical small acinar proliferation
    • Atypical hyperplastic appearing glands
    • Postradiation prostatic adenocarcinoma with treatment effect
    • Differentiation of invasive cribriform carcinoma from intraductal carcinoma / atypical intraductal proliferation / atypical cribriform lesion
  • Confirming prostatic origin of disseminated / metastatic carcinoma (Arch Pathol Lab Med 2020;144:290, Mod Pathol 2018;31:S12)
  • Markers for primary prostatic neoplasia (Arch Pathol Lab Med 2020;144:290, Mod Pathol 2018;31:S12, Adv Anat Pathol 2018;25:387, Am J Clin Pathol 2020;153:407):
    • Triple antibody cocktail (PIN cocktail): most widely used
    • ERG: highly specific (in the setting of absence of basal cells) but not sensitive for prostatic adenocarcinoma
    • Acinar prostatic adenocarcinoma:
      • Positive staining:
        • AMACR / p504s (often, ~80%)
      • Negative staining:
        • p63, 34 beta E12 (no basal cells)
    • Ductal adenocarcinoma
      • Positive staining:
        • AMACR / p504s (often, ~80%)
      • Negative staining:
        • p63, 34 beta E12 (no basal cells)
      • Can occasionally be p63 and 34 beta E12 positive (focal / sparse basal cells)
    • Intraductal carcinoma / atypical intraductal proliferation / atypical cribriform lesion / carcinoma in situ
      • Positive staining:
        • AMACR / p504s (often, ~80%)
        • p63, 34 beta E12 (continuous or discontinuous layer of basal cells)
  • Markers for prostatic origin of disseminated / metastatic carcinoma
    • Positive staining:
      • NKX3.1, AR: highly sensitive and specific
      • ERG, PSA, prostein: highly specific, moderately sensitive
      • PSMA: moderately specific and sensitive
      • Others:
        • CK7, CK20:
          • Negative in low grade prostatic carcinoma
          • Negative or focally positive in high grade prostatic carcinoma
        • CDX2 can be positive
    • Negative staining:
      • PAX8, PAX2, TTF1, GATA3, 34 beta E12, p63, p40
Microscopic (histologic) description
  • Nuclear markers: AR (androgen receptor), NKX3.1, p63, ERG
  • Cytoplasmic markers: AMACR / p504s (alpha methylacyl CoA racemase), PSA, prostein / p501s
  • Cytoplasmic and membrane markers: 34 beta E12 (also called cytokeratin 903), PSMA (prostate specific membrane antigen)
Microscopic (histologic) images

Contributed by Guang-Qian Xiao, M.D., Ph.D.


Prostatic adenocarcinoma

Atypical cribriform lesion

Prostatic adenocarcinoma

Partial atrophy

Carcinoma with radiation effect

Positive staining - normal
Sample pathology report
  • For primary atypical prostatic glands: IHCs reveal atypical prostatic glands negative for p63 and 34 beta E12 (absence of basal cells) and positive for AMACR / p504s, supporting the diagnosis of prostatic adenocarcinoma
  • For disseminated tumor: IHCs reveal tumor cells positive for NKX3.1, PSA and AR, supporting prostatic origin
Differential diagnosis
Board review style question #1
Which is the most sensitive marker for prostate origin?

  1. ERG
  2. NKX3.1
  3. P504s / AMACR
  4. PSA
Board review style answer #1
Board review style question #2

Which of the following lesions in the prostate can present with no basal cell layer?

  1. High grade PIN
  2. Intraductal carcinoma
  3. Partial atrophy
  4. Atypical cribriform lesion
Board review style answer #2
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