[932] Histone 1.5: A Novel Prostatic Cancer Marker Superior to AMACR: An Immunohistochemical Study

Vadim Khachaturov, Guang-Qian Xiao, Yayoi Kinoshita, Pamela D Unger, David E Burstein. Mount Sinai School of Medicine, New York, NY

Background: Histone H1.5 (HH1.5) is part of the linker histone families, which is located in the nucleus and plays a role in chromatin structure and gene expression. HH1.5 is expressed more in pluripotent cells than in differentiated cells and may contribute in self-renewal mechanisms. AMACR is frequently used to distinguish benign from malignant prostatic lesions with approximately 25% false positive and false negative results. The aim of this study was to investigate the diagnostic and prognostic role of HH1.5 in prostatic cancer.
Design: Sixty-nine routinely formalin fixed and paraffin embedded prostatic needle biopsies were immunohistochemically stained for HH1.5 (1:800), of which 67 cases had prostatic cancer, ranging from Gleason 3 to 5. High grade prostatic intraepithelial neoplasia (HPIN) was also evaluated when present in the specimen. Nuclear staining of HH1.5 was considered positive.
Results: The majority of prostatic cancer cases (91%) showed strong reactivity for HH1.5. In contrast, only 10% of benign prostatic glands showed focal weak positivity. HPIN also stained focally and weakly for HH1.5. In addition, increased HH1.5 staining was observed in high grade prostatic cancer versus lower grade (74% vs 59%). Background lymphocytes when present were uniformly and strongly reactive with HH1.5. The results are summarized in Tables 1 and 2.

Table 1. Histone H1.5 in Prostate Cancer, HPIN & Benign Glands
 Gleason 3/4/5BenignHPIN
HH1.561∗ (91%)7† (10%)23‡ (100%)
Total676923
∗ strong positive, † weak positive, ‡ mostly weak positive



Table 2. Histone H1.5 Intensity: Gleason 3 vs 4/5 vs Metastatic Cancer
IntensityGleason 3Gleason 4/5Metastatic
Neg.4 (7%)6 (14%)1
1+19 (34%)5 (12%)0
2+33 (59%)32 (74%)4 (80%)
3+56435∗
Neg. 0-10%, 1+ 11-50%, 2+ > 50%, ∗ All cases were Gleason 4 or 5


Conclusions: Our results demonstrated that HH1.5 immunohistochemical staining distinguished prostate cancer from benign prostate glands with superior sensitivity and specificity to AMACR. HH1.5 showed 9% false negative results versus approximately 25% seen in AMACR and 10% false positive staining versus approximately 25% seen with AMACR. Additionally, more intense staining was noted in high grade cancer (Gleason 4/5) and metastatic cases than low grade cancers (Gleason 3), implying a role in predicting the aggressiveness of this tumor. Further studies verifying the potential diagnostic and prognostic value of HH1.5 are needed. Clean nuclear reactivity of HH1.5 and background lymphocytes as a positive control are additional advantages of this marker for practical use.
Category: Genitourinary (including renal tumors)

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 136, Monday Morning

 

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