Diagnosis of Atypical Prostate Glandular Proliferation
Diagnosis of Atypical Prostate Glandular Proliferation
We evaluated the diagnostic usefulness of the 34βE12-p63 cocktail, compared with 34βE12 and p63 used alone, in 34 prostate needle biopsy (NBXs) and 3 transurethral resection specimens containing atypical glandular proliferations and in 18 NBXs containing unequivocal prostate carcinoma (PCa). Staining intensity; percentage of basal cells staining in benign, atypical, and malignant glands; number of benign glands lacking basal cell staining; and staining variance were analyzed. All NBXs with unequivocal PCa were negative with all 3 markers. Diagnoses were as follows for the atypical cases after staining for the 3 markers: PCa, 9; postatrophic hyperplasia, 12; high-grade prostatic intraepithelial neoplasia (HGPIN), 5; atypical adenomatous hyperplasia, 6; benign atypical proliferations, 4; and HGPIN with adjacent small atypical acinar proliferation suggestive of PCa, 1. The cocktail demonstrated consistently strong staining intensity and improved basal cell staining in morphologically benign and benign atypical glands compared with p63 and 34βE12 alone; it had the smallest staining variance compared with 34βE12 (F < 0.0001) and p63 (F = 0.31), although its advantage for resolving individual atypical cases was limited compared with 34βE12 and p63 alone. Of 37 atypical cases, 1 (3%) additionally was resolved as benign using the cocktail and p63. Because the diagnosis of PCa is supported by lack of basal cell staining, the immunohistochemical analysis with highest possible sensitivity and lowest possible variability is critical to ensure that a negative reaction is true. The cocktail provides a simple, cost-effective improvement in basal cell immunohistochemical analysis of difficult prostate lesions.
Widespread use of prostate-specific antigen screening has led to an increase in prostate needle biopsies and, subsequently, an increase in earlier detection of prostate carcinoma (PCa). This trend also has led to an increase in the number of equivocal diagnoses on prostate biopsy specimens. Surgical pathologists must make critical decisions on an increasing number of prostate needle biopsy specimens with only small foci of atypical glands. In this setting, the mimics of PCa must be distinguished from a small focus of adenocarcinoma.
The basal cell marker, high-molecular-weight cytokeratin antibody (34βE12) is used widely in this setting. Recent studies have shown p63, a p53 homologue, to be a useful basal cell marker. Diagnosis of PCa using both basal cell markers is supported by the lack of basal cell staining in atypical glands. However, the diagnosis using basal cell immunohistochemical analysis might not always be conclusive because the absence of staining or only patchy staining can occur, particularly in some benign and premalignant prostate lesions such as atypical adenomatous hyperplasia (AAH), high-grade prostatic intraepithelial neoplasia (HGPIN), and postatrophic hyperplasia (PAH).
Recent work comparing both basal cell markers demonstrated that 34βE12 and p63 are subject to some staining variability, although p63 staining has less variability. Because the diagnosis of PCa is supported by lack of basal cell staining, it is critical to use the basal cell marker with highest possible sensitivity and lowest variability to ensure that negative staining is truly due to lack of basal cells and not to technical problems. To improve confidence in basal cell immunohistochemical analysis, p63 frequently is used in addition to 34βE12 in difficult prostate lesions. Zhou et al recently demonstrated that the combined use of 34βE12 and p63 as a cocktail improves basal cell detection in benign prostate glands from the transition zone compared with each used separately. The goal of the present study was to evaluate the usefulness of the basal cell cocktail in the workup of clinically atypical cases.
We evaluated the diagnostic usefulness of the 34βE12-p63 cocktail, compared with 34βE12 and p63 used alone, in 34 prostate needle biopsy (NBXs) and 3 transurethral resection specimens containing atypical glandular proliferations and in 18 NBXs containing unequivocal prostate carcinoma (PCa). Staining intensity; percentage of basal cells staining in benign, atypical, and malignant glands; number of benign glands lacking basal cell staining; and staining variance were analyzed. All NBXs with unequivocal PCa were negative with all 3 markers. Diagnoses were as follows for the atypical cases after staining for the 3 markers: PCa, 9; postatrophic hyperplasia, 12; high-grade prostatic intraepithelial neoplasia (HGPIN), 5; atypical adenomatous hyperplasia, 6; benign atypical proliferations, 4; and HGPIN with adjacent small atypical acinar proliferation suggestive of PCa, 1. The cocktail demonstrated consistently strong staining intensity and improved basal cell staining in morphologically benign and benign atypical glands compared with p63 and 34βE12 alone; it had the smallest staining variance compared with 34βE12 (F < 0.0001) and p63 (F = 0.31), although its advantage for resolving individual atypical cases was limited compared with 34βE12 and p63 alone. Of 37 atypical cases, 1 (3%) additionally was resolved as benign using the cocktail and p63. Because the diagnosis of PCa is supported by lack of basal cell staining, the immunohistochemical analysis with highest possible sensitivity and lowest possible variability is critical to ensure that a negative reaction is true. The cocktail provides a simple, cost-effective improvement in basal cell immunohistochemical analysis of difficult prostate lesions.
Widespread use of prostate-specific antigen screening has led to an increase in prostate needle biopsies and, subsequently, an increase in earlier detection of prostate carcinoma (PCa). This trend also has led to an increase in the number of equivocal diagnoses on prostate biopsy specimens. Surgical pathologists must make critical decisions on an increasing number of prostate needle biopsy specimens with only small foci of atypical glands. In this setting, the mimics of PCa must be distinguished from a small focus of adenocarcinoma.
The basal cell marker, high-molecular-weight cytokeratin antibody (34βE12) is used widely in this setting. Recent studies have shown p63, a p53 homologue, to be a useful basal cell marker. Diagnosis of PCa using both basal cell markers is supported by the lack of basal cell staining in atypical glands. However, the diagnosis using basal cell immunohistochemical analysis might not always be conclusive because the absence of staining or only patchy staining can occur, particularly in some benign and premalignant prostate lesions such as atypical adenomatous hyperplasia (AAH), high-grade prostatic intraepithelial neoplasia (HGPIN), and postatrophic hyperplasia (PAH).
Recent work comparing both basal cell markers demonstrated that 34βE12 and p63 are subject to some staining variability, although p63 staining has less variability. Because the diagnosis of PCa is supported by lack of basal cell staining, it is critical to use the basal cell marker with highest possible sensitivity and lowest variability to ensure that negative staining is truly due to lack of basal cells and not to technical problems. To improve confidence in basal cell immunohistochemical analysis, p63 frequently is used in addition to 34βE12 in difficult prostate lesions. Zhou et al recently demonstrated that the combined use of 34βE12 and p63 as a cocktail improves basal cell detection in benign prostate glands from the transition zone compared with each used separately. The goal of the present study was to evaluate the usefulness of the basal cell cocktail in the workup of clinically atypical cases.
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