Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: Review of current literature

University of Wales, Cardiff, Wales, United Kingdom
Histopathology (Impact Factor: 3.45). 07/2005; 47(1):1-16. DOI: 10.1111/j.1365-2559.2005.02188.x
Source: PubMed


Varma M & Jasani B (2005) Histopathology47, 1-16 Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: review of current literatureImmunohistochemistry is widely used to distinguish prostate cancer from benign mimics and to establish the prostatic origin of poorly differentiated carcinoma. We critically review the recent advances in prostate cancer immunohistochemistry, including the introduction of newer basal cell markers such as p63 and the discovery of the overexpression of alpha-methylacyl coenzyme A racemase (AMACR) in prostate cancer. The description of newer urothelial markers to aid the distinction of prostate cancer from urothelial carcinoma is also presented together with refinements in the quality control of PSA and PSAP immunostaining. Although AMACR is a useful immunohistochemical marker for prostate cancer, it has significant limitations. These limitations are discussed and the need for interpreting AMACR immunoreactivity in the appropriate morphological context and in conjunction with basal call markers is emphasized. We also describe the utility of an immunohistochemical panel composed of PSA, PSAP and high molecular weight cytokeratin for distinguishing poorly differentiated prostate cancer from high-grade urothelial carcinoma. A morphological differential diagnosis based selection of immunohistochemical markers is highlighted as a novel approach in the diagnosis of prostate cancer in routine surgical pathology practice.

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    • "Morphological analysis is routinely used to diagnose prostate cancer, although IHC is used to assist morphological diagnosis, particularly in equivocal cases, e.g. in tissue samples from needle biopsies, transurethral resection specimens and metastatic tumor samples [19]. A complicating issue hindering discovery of new biomarkers for diagnosis and disease stratification of prostate (and other) cancer(s) from biopsy samples, has been a dearth of unbiased, quantitative methods to detect significant changes from IHC experiments for biomarker identification. "
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    ABSTRACT: Prostate carcinoma is the most common cancer in men with few, quantifiable, biomarkers. Prostate cancer biomarker discovery has been hampered due to subjective analysis of protein expression in tissue sections. An unbiased, quantitative immunohistochemical approach provided here, for the diagnosis and stratification of prostate cancer could overcome this problem. Antibodies against four proteins BTF3, HINT1, NDRG1 and ODC1 were used in a prostate tissue array (> 500 individual tissue cores from 82 patients, 41 case pairs matched with one patient in each pair had biochemical recurrence). Protein expression, quantified in an unbiased manner using an automated analysis protocol in ImageJ software, was increased in malignant vs non-malignant prostate (by 2-2.5 fold, p<0.0001). Operating characteristics indicate sensitivity in the range of 0.68 to 0.74; combination of markers in a logistic regression model demonstrates further improvement in diagnostic power. Triple-labeled immunofluorescence (BTF3, HINT1 and NDRG1) in tissue array showed a significant (p<0.02) change in co-localization coefficients for BTF3 and NDRG1 co-expression in biochemical relapse vs non-relapse cancer epithelium. BTF3, HINT1, NDRG1 and ODC1 could be developed as epithelial specific biomarkers for tissue based diagnosis and stratification of prostate cancer.
    PLoS ONE 12/2013; 8(12):e84295. DOI:10.1371/journal.pone.0084295 · 3.23 Impact Factor
    • "However, a small subset of metastatic prostate cancers that are usually poorly differentiated show only a weak or negative PSA stain.[316] In recent years, the prostate biomarker Alpha-Methylacyl-CoA-Racemase (P504s) has been used as an adjuvant to morphology in diagnostically challenging cases, with a very high sensitivity and specificity ranging from 82-100%.[1718] In our case, the fine needle aspiration only interpreted it as poorly differentiated adenocarcinoma. "
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    ABSTRACT: Cervical regional nodal involvement, as the first manifestation of prostatic cancer, has been rarely reported. Prostate cancer metastasis to the supraclavicular lymph nodes with negative immunohistochemical stain of PSA is even rarer. We report a case of prostate cancer with negative immunohistochemical stain of prostate-specific antigen presenting with left supraclavicular node enlargement. A 63-year-old man was referred to our hospital for a left supraclavicular mass. He had a family history of gastric cancer (two brothers had died of gastric cancer). Enhanced computed tomography of the abdomen revealed retroperitoneal lymph node enlargement. Gastroscopy revealed no evidence of any gastric tumor. Biopsy of the left-sided supraclavicular lymph nodes revealed metastatic adenocarcinoma with a negative prostate-specific antigen (PSA) stain. The serum tumor markers were examined, revealing PSA levels of 21.820 ng/ml. Biopsy of the prostate disclosed poorly-to-moderately differentiated adenocarcinoma (Gleason 4 + 4 = 8). Although rare, prostate cancer should be considered in the differential diagnoses of elderly men with undetermined original adenocarcinoma, metastatic to the supraclavicular lymph nodes. Rectal examination, serum PSA and pelvic image can be helpful to lead the diagnosis. PSA stain may be weak or negative in some poorly differentiated patients, however, it is still a sensitive and specific marker of prostatic differentiation and must be routinely applied.
    Journal of research in medical sciences 09/2013; 18(9):814-7. · 0.65 Impact Factor
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    • "These findings raised again the question whether this is truly metastatic prostatic adenocarcinoma. It has been suggested that rarely several non-prostatic tumors such as salivary gland neoplasms, malignant melanoma, adenocarcinoma of paraurethral glands (Skene's), urothelial carcinoma may show PSA positivity [49]. However, on clinical, CT and MRI evaluation there was no evidence of any of the above mentioned tumours in our patient. "
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    ABSTRACT: AimThe current paper describes a case of prostatic adenocarcinoma metastatic to the skin presenting as an extrammamary Paget's disease, a very rare and poorly characterised morphological entity. We report a case of prostatic carcinoma metastatic to skin showing a pattern of extramammary Paget's disease which has not been clearly illustrated in the literature Case presentation: A 63 year-old man with prostatic adenocarcinoma developed cutaneous metastases after 16 years. The inguinal metastases were sessile and 'keratotic.' The tumour displayed solid, glandular areas as well as a polypoid region suggestive of extramammary Paget's disease were identified.Discussion and conclusionsWe review the diagnostic criteria that have led to the correct histopathological diagnosis in this case. A differential diagnosis of the pagetoid spread in the skin and various forms of cutaneous metastases determined by a prostatic adenocarcinoma as well as the role of immunohistochemistry in establishing the prostatic origin are presented in the context of this case. Although, morphologically the cells presented in the skin deposits were not characteristic for adenocarcinoma of prostate, immunohistochemistry for PSA and PSAP suggested a prostatic origin.Virtual SlidesThe virtual slide(s) for this article can be found here:
    Diagnostic Pathology 08/2012; 7(1):106. DOI:10.1186/1746-1596-7-106 · 2.60 Impact Factor
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