Immunohistochemical Expression of NKX3.1 in Prostatic Adenocarcinoma Correlates with Tumors Grade among Sudanese (original) (raw)
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Journal of Gandhara medical and dental sciences, 2023
All specimens were subjected to immunohistochemical staining with NKX3.1. Statistical analysis was done by using SPSS version 23.0. The association of the extent of NKX3.1 staining between the adenocarcinoma and hyperplasia group was assessed using the Chi-square test x2. RESULTS Of the 37 cases of benign prostatic hyperplasia subjected to NKX3.1 staining, 32 showed positive staining with strong to moderate intensity. No staining was observed in 5 cases. 37 cases of adenocarcinoma prostate stained for NKX3.1 revealed positive staining in 30 cases with strong to moderate intensity. Negative staining was seen in 7 cases. The prostatic adenocarcinoma showed a statistically signicant association of NKX3.1 positivity compared to benign prostatic hyperplasia cases. The p-value was found to be 0.03. CONCLUSION NKX3.1 staining was highly specic for prostate epithelium, as it was positive in most cases. This immune marker was useful for distinguishing prostatic origin in the context of metastatic lesions. Adding NKX3.1 protein staining to a panel of features may add value to the diagnosis if applied in the appropriate clinicopathologic context.
NKX3.1 as a marker of prostatic origin in metastatic tumors.
2010
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). A recent study showed that NKX3.1 staining with a novel antibody was 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. The purpose of this study was to determine the performance of NKX3.1 as a marker of metastatic adenocarcinoma of prostatic origin. Immunohistochemical staining against NKX3.1, PSA, and PSAP was carried out on a tissue microarray (TMA) (0.6-mm tissue cores) of hormone naïve metastatic prostate adenocarcinoma specimens from lymph nodes, bone, and soft tissue. To determine the specificity of NKX3.1 for prostatic adenocarcinoma, we used TMAs that contained cancers from various sites including the urinary bladder, breast, colon, salivary gland, stomach, pancreas, thyroid, and central nervous system, and standard paraffin sections of cancers from other sites including the adrenal cortex, kidney, liver, lung, and testis. Overall 349 nonprostatic tumors were evaluated. Any nuclear staining for NKX3.1 was considered positive and the percentage of cells with nuclear staining and their mean intensity level were assessed visually. Sensitivity was calculated by considering a case positive if any TMA core was positive. The sensitivity for identifying metastatic prostatic adenocarcinomas overall was 98.6% (68/69 cases positive) for NKX3.1, 94.2% (65/69 cores positive) for PSA, and 98.6% (68/69 cores positive) for PSAP. The specificity of NKX3.1 was 99.7% (1/349 nonprostatic tumors positive). The sole positive nonprostatic cancer case was an invasive lobular carcinoma of the breast. 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.
Cancer Research, 2006
NKX3.1 is a homeobox gene located at chromosome 8p21.2, and one copy is frequently deleted in prostate carcinoma. Prior studies of NKX3.1 mRNA and protein in human prostate cancer and prostatic intraepithelial neoplasia (PIN) have been conflicting, and expression in focal prostate atrophy lesions has not been investigated. Immunohistochemical staining for NKX3.1 on human tissue microarrays was decreased in most focal atrophy and PIN lesions. In carcinoma, staining was inversely correlated with Gleason grade. Fluorescence in situ hybridization showed that no cases of atrophy had loss or gain of 8p, 8 centromere, or 8q24 (C-MYC) and only 12% of highgrade PIN lesions harbored loss of 8p. By contrast, NKX3.1 staining in carcinoma was correlated with 8p loss and allelic loss was inversely related to Gleason pattern. Quantitative reverse transcription-PCR for NKX3.1 mRNA using microdissected atrophy revealed a concordance with protein in five of seven cases. In carcinoma, mRNA levels were decreased in 6 of 12 cases but mRNA levels correlated with protein levels in only 4 of 12 cases, indicating translational or posttranslational control. In summary, NKX3.1 protein is reduced in focal atrophy and PIN but is not related to 8p allelic loss in these lesions. Therefore, whereas genetic disruption of NKX3.1 in mice leads to PIN, nongenetic mechanisms reduce NKX3.1 protein levels early in human prostate carcinogenesis, which may facilitate both proliferation and DNA damage in atrophic and PIN cells. Monoallelic deletions on chromosome 8p are associated with more advanced invasive and aggressive disease.
Cancer research, 2002
NKX3.1, a member of the NK class of homeodomain proteins, is expressed primarily in the adult prostate and has growth suppression and differentiating effects in prostate epithelial cells. A C-->T polymorphism at nucleotide 154 (NKX3.1 C154T) is present in approximately 11% of healthy men with equal distribution among whites and blacks. In a cohort of 1253 prostate cancer patients and age-matched controls, the presence of the polymorphism was associated with a 1.8-fold risk of having stage C or D prostate cancer or Gleason score > or =7 (confidence interval, 1.01-3.22). The NKX3.1 C154T polymorphism codes for a variant protein that contains an arginine-to-cysteine substitution at amino acid 52 (R52C) adjacent to a protein kinase C phosphorylation site at serine 48. Substitution of cysteine for arginine 52 or of alanine for serine 48 (S48A) reduced phosphorylation at serine 48 in vitro and in vivo. Phosphorylation of wild-type NKX3.1, but not of NKX3.1 R52C or NKX3.1 S48A, dimin...
Evaluation of some tissue and serum biomarkers in prostatic carcinoma among Egyptian males
Clinical Biochemistry, 1999
The purpose of this study is to evaluate the role of soluble E-cadherin as a serum marker and bcl-2 and DNA content as tissue markers in characterization and management of prostatic adenocarcinoma (PC) among Egyptian males. Design and Methods: The study group included 71 patients with prostatic adenocarcinoma, 30 patients with benign prostatic hyperplasia (BPH), and 20 normal male subjects. Serum soluble Ecadherin (sE-cadherin) and PSA were quantified by ELISA and MEIA (microparticle enzyme immunoassay) techniques, respectively. Tissue samples were investigated for bcl-2 chromosomal translocation t(14;18) by polymerase chain reaction (PCR) together with detection of bcl-2 protein expression by immunohistochemistry. The results were correlated with DNA content (as defined by flow cytometric analysis) and also with traditional clinicopathologic parameters. Results: Our data revealed that, serum PSA was superior to sE-cadherin as a marker for PC with a sensitivity of 83% compared to 59% in case of E-cadherin at the same specificity (96.6%)
medicallaboratory journal, 2019
Background and Objectives: Prostate cancer is a highly prevalent malignancy with a high mortality rate in men. Many studies have investigated the diagnostic value of various genes involved in prostate cancer, but there is no data for Kallikrein 2 (KLK2) and Kallikrein 3 (KLK3) expression patterns among Iranian patients. Therefore, we aimed to evaluate the expression of these two genes in Iranian patients with prostate cancer. Methods: In this case-control study, three groups consisting of healthy individuals, patients with benign prostatic hyperplasia (BPH) and patients with prostate cancer were studied. Peripheral blood samples were collected from all subjects, mRNA was extracted after cell lysis, and cDNA was synthesized. Real-time PCR was performed to assess gene expression levels relative to a reference gene (18s rRNA gene). Results: The KLK2 gene was overexpressed in patients with prostate cancer. KLK2 expression differed significantly between the cancer patients and controls. Relative expression of the KLK3 gene in the BPH group was higher than that in the control and cancer groups. However, we observed no significant difference in the expression of KLK3 between the control and cancer subjects. Conclusion: We demonstrate that analysis of KLK2 expression is a favorable method of diagnosing prostate cancer and discriminating normal individuals from those with BPH or prostate cancer. We also found that the KLK3 gene is highly overexpressed in individuals with BPH, which might indicate that this gene is not cancer-specific.