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NKX3A

MIM.602041 8p21 HGNC:7838

Wednesday 31 January 2007

Definition: The homeodomain-containing transcription factor NKX3A is a putative prostate tumor suppressor that is expressed in a largely prostate-specific and androgen-regulated manner.

NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p.

Although most studies have shown that staining for NKX3.1 protein is positive in the majority of primary prostatic adenocarcinomas, it has been shown to be downregulated in many high-grade prostate cancers, and completely lost in the majority of metastatic prostate cancers (eg, in 65% to 78% of lesions).

NKX3.1 staining with a novel antibody is highly sensitive and specific for high-grade prostatic adenocarcinoma when compared with high-grade urothelial carcinoma.

This raised the question that this antibody may perform better than earlier used antibodies in metastatic prostate tumors. However, the sensitivity and specificity for prostate carcinomas for this antibody in metastatic lesions was not determined.

Although prostate-specific antigen (PSA) and prostatic-specific acid phosphatase (PSAP) are excellent tissue markers of prostate cancer, at times they may be expressed at low levels, focally, or not at all in poorly differentiated primary and metastatic prostatic adenocarcinomas.

NKX3.1 seems to be a highly sensitive and specific tissue marker of metastatic prostatic adenocarcinoma. In the appropriate clinical setting, the addition of IHC staining for NKX3.1, along with other prostate-restricted markers, may prove to be a valuable adjunct to definitively determine prostatic origin in poorly differentiated metastatic carcinomas.

Pathology

- Loss of NKX3A protein expression is a common finding in human prostate carcinomas and prostatic intraepithelial neoplasia. (20588175)

Cytogenetics

- Monoallelic deletions on chromosome 8p are associated with more advanced invasive and aggressive disease (17108105)

Open References

- NKX3.1 as a marker of prostatic origin in metastatic tumors. Gurel B, Ali TZ, Montgomery EA, Begum S, Hicks J, Goggins M, Eberhart CG, Clark DP, Bieberich CJ, Epstein JI, De Marzo AM. Am J Surg Pathol. 2010 Aug;34(8):1097-105. PMID: 20588175 (Free)

References

- Decreased NKX3.1 protein expression in focal prostatic atrophy, prostatic intraepithelial neoplasia, and adenocarcinoma: association with gleason score and chromosome 8p deletion. Bethel CR, Faith D, Li X, Guan B, Hicks JL, Lan F, Jenkins RB, Bieberich CJ, De Marzo AM. Cancer Res. 2006 Nov 15;66(22):10683-90. PMID: 17108105

- A novel human prostate-specific, androgen-regulated homeobox gene (NKX3.1) that maps to 8p21, a region frequently deleted in prostate cancer. He, W. W.; Sciavolino, P. J.; Wing, J.; Augustus, M.; Hudson, P.; Meissner, P. S.; Curtis, R. T.; Shell, B. K.; Bostwick, D. G.; Tindall, D. J.; Gelmann, E. P.; Abate-Shen, C.; Carter, K. C. . Genomics 43: 69-77, 1997. PubMed ID : 9226374