Do HOXB13 and P63 have a role in differentiating poorly differentiated prostatic carcinoma from urothelial high‐grade carcinoma?

Abstract

Poorly differentiated prostatic carcinoma may overlap with high-grade urothelial carcinoma; a distinction is a must as treatments differ. This study aims to evaluate traditional (PSA and HMWCK) and relatively novel (P63 and HOXB13) markers in distinguishing them; and to evaluate their role in the diagnosis of challenging cases. Sections from: diagnosed group includes 65 prostatic and urothelial carcinoma cases were stained with PSA, HMWCK, P63, and HOXB13. Sensitivity, specificity, and accuracy were evaluated. The second group includes 25 challenging cases which were stained first by PSA and HMWCK, then solved the problematic cases with P63 and HOXB13. PSA and HMWCK were sensitive and specific for prostatic and urothelial carcinomas, respectively, but the sensitivity and accuracy were higher for P63 and HOXB13. By using the traditional markers, 17 cases were diagnosed in the second group while the remaining eight cases need the novel markers to be diagnosed. A confident diagnosis can be established in the majority of cases of poorly differentiated carcinoma in either prostatic or urothelial by using a panel of PSA and HMWCK. In some problematic cases, an extended panel including P63 and HOXB13 is helpful in resolving the diagnosis.

HOXB13 as an immunohistochemical marker of prostatic origin in metastatic tumors

“…As a matter of fact, staining for this antigen was observed in only two metastases from urothelial carcinoma and in none from colorectal, hepatocellular, and lung carcinomas. Our findings slightly differ from those previously reported by other authors who showed that HOXB13 is 100% specific for prostate cancer in the differential diagnosis toward urothelial carcinoma (14,15). We used 10% of stained neoplastic cells as a cut-off value for the definition of positive cases in order to make our results comparable with those achieved by other authors (14).…”

“…A similar finding was previously reported by Alshenawy and coll. (15) who found that HOXB13 can discriminate between prostatic and urothelial carcinoma with 100% sensitivity. Expression of HOXB13 in 100% of metastatic tumors is in line with the more frequent expression of this factor in high grade primitive prostatic carcinomas (16).…”

“…With reference to HOXB13 immunoreaction, tumors that showed nuclear staining of at least 10% of the cells were recorded as positive, while cases with staining of <10% of the cells were classified as negative . The intensity of the staining was estimated as weak or strong .…”

“…Homeobox B13 (HOXB13) is a transcription factor which is involved in prostate development during embryogenesis and retained in the glandular prostatic epithelium in the adult . This factor is also expressed in prostate cancer and significantly associated with advanced pT stage, high Gleason grade, positive lymph node status, and adverse prognosis in this tumor . Of note, HOXB13 was shown to co‐localize with AR and to repress its downstream signaling in both normal and neoplastic prostatic epithelium .…”

“…Aside from its prognostic role, the expression of HOXB13 in prostatic cancer seems to have relevant diagnostic value. Indeed, HOXB13 was recently demonstrated to be a sensitive and specific marker for prostate cancer in the differential diagnosis toward urothelial carcinoma . To the best of our knowledge, the diagnostic relevance of HOXB13 for detection of prostatic origin of metastatic tumors has not been explored thus far.…”