Abstract
Aims: Determining the origin of metastases is an important task of pathologists to allow for the initiation of a tumor-specific therapy. Recently, homeobox protein Hox-B13 (HOXB13) has been suggested as a new marker for the detection of prostatic origin. The aim of this study was to evaluate the diagnostic sensitivity of HOXB13 in comparison to commonly used immunohistochemical markers for prostate cancer. Materials and methods: Histologically confirmed prostate cancer lymph node metastases from 64 cases were used to test the diagnostic value of immunohistochemical markers: prostate specific antigen (PSA), Prostatic acid phosphatase (PSAP), prostate specific membrane antigen (PSMA), homeobox gene NKX3.1, prostein, androgen receptor (AR), HOXB13, and ETS-related gene (ERG). All markers were evaluated semi-quantitatively using Remmele’s immune reactive score. Results: The detection rate of prostate origin of metastasis for single markers was 100% for NKX3.1, 98.1% for AR, 84.3% for PSMA, 80.8% for PSA, 66% for PSAP, 60.4% for HOXB13, 59.6% for prostein, and 50.0% for ERG. Conclusions: Our data suggest that HOXB13 on its own lacks sensitivity for the detection of prostatic origin. Therefore, this marker should be only used in conjunction with other markers, preferably the highly specific PSA. The combination of PSA with NKX3.1 shows a higher sensitivity and thus appears preferable in this setting.
Highlights
Determining the origin of the primary tumor in metastases is an important task of pathologists to allow for the initiation of a tumor-specific therapy
Nuclear staining was seen for the androgen receptor (AR), ETS-related gene (ERG), INntK
This study evaluates the sensitivity of prostate markers to detect lymph node and distant metastases of prostate cancer
Summary
Determining the origin of the primary tumor in metastases is an important task of pathologists to allow for the initiation of a tumor-specific therapy. PSA is still regarded as a highly specific marker of prostatic origin, but due to its decreased or even lost expression in higher grade or metastatic tumors, which was already noted in initial studies, its sensitivity is clearly limited, which necessitates the use of additional markers in PSA negative cases [5]. Prostein, coded by the SLC45A3 gene and identified by transcript profiling studies of prostate cancer, was found to be highly specific for prostatic origin and displays a characteristic Golgi-type cytoplasmic staining pattern [6,7]. An alternative marker for prostatic origin was the protein coded by the homeobox gene NKX3.1, which shows nuclear staining on immunohistochemistry and which was found to be highly though not exclusively specific for prostate tissues [10,11]. At the 2014 consensus conference of the International Society of Urological Pathology (ISUP), it was recommended to use immunohistochemistry for PSA, NKX3.1 and prostein to ascertain a prostatic origin in doubtful cases [5]
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