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Prostate gland & seminal vesicles

IHC overview

Authors: Brian Ma, M.D., Guang-Qian Xiao, M.D., Ph.D.

Editorial Board Member: Maria Tretiakova, M.D., Ph.D.

Editor-in-Chief: Debra L. Zynger, M.D.

Last author update: 23 October 2020

Last staff update: 9 June 2023

Copyright: 2003-2024, PathologyOutlines.com, Inc.

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

Table of Contents

Cite this page: Ma B, Xiao GQ. IHC overview. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/prostateihc.html. Accessed December 23rd, 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)

Terminology

Triple antibody cocktail (also called PIN4 or PIN cocktail): mixture of p63, 34 beta E12 and AMACR / P504s

Pathophysiology

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.

Adenosis

Prostatic adenocarcinoma

Atypical cribriform lesion

Prostatic adenocarcinoma

Partial atrophy

Carcinoma with radiation effect

Positive staining - normal

Prostate:
- Basal cells: p63, 34 beta E12
- Luminal cells: PSA, prostein, PSMA, NKX3.1, AR
- Neuroendocrine cells: chromogranin, synaptophysin, CD56
Seminal vesicles:
- AR, PAX8, p63 and 34 beta E12
References: Mod Pathol 2018;31:S12, Adv Anat Pathol 2018;25:387

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

Benign immunohistochemical mimickers of prostatic carcinoma - small acini without or patchy for basal cells (p63 and 34 beta E12 negative) (Arch Pathol Lab Med 2020;144:290, Mod Pathol 2018;31:S12, Adv Anat Pathol 2018;25:387):
- Adenosis
- Partial atrophy
- AMACR can be weakly positive
- ERG if positive supports prostatic adenocarcinoma
Prostate cancer, when involving bladder, not infrequently misdiagnosed as urothelial carcinoma if immunohistochemistry not performed (Arch Pathol Lab Med 2020;144:290, Adv Anat Pathol 2018;25:387):
- Positive for prostatic carcinoma: NKX3.1, AR, ERG, PSA, PSMA, prostein
- Positive for urothelial carcinoma: GATA3, p63, CK5/6, 34 beta E12

Board review style question #1

Which is the most sensitive marker for prostate origin?

ERG
NKX3.1
P504s / AMACR
PSA

Board review style answer #1

B. NKX3.1

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Reference: Prostate gland & seminal vesicles - Immunohistochemistry

Board review style question #2

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

High grade PIN
Intraductal carcinoma
Partial atrophy
Atypical cribriform lesion

Board review style answer #2

C. Partial atrophy

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Reference: Prostate gland & seminal vesicles - Immunohistochemistry

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