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: 2003-2023, PathologyOutlines.com, Inc.
PubMed Search: prostate[title] immunohistochemistry[title] pathology
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Uses by pathologists | Microscopic (histologic) description | Microscopic (histologic) images | Positive staining - normal | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Ma B, Xiao GQ. IHC overview. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/prostateihc.html. Accessed September 30th, 2023.
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)
- Positive staining:
- 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)
- Positive staining:
- 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)
- Positive staining:
- 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
- CK7, CK20:
- Negative staining:
- PAX8, PAX2, TTF1, GATA3, 34 beta E12, p63, p40
- Positive staining:
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
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
