Expression of nm23 antimetastatic gene product in prostate carcinoma in Saudi patients and its relation to chromosomal instability

ABSTRACT

The nm23 gene was initially cloned as a metastasis suppressor gene, but the clinical relevance of nm23 as a prognostic indicator for human cancers remains controversial. Chromosomal instability [CIN] is a high frequency of chromosomal loss and gain that has been demonstrated in dysplastic and neoplastic lesions. Recently CIN has been shown in prostate carcinoma [Pca] and its precursor. The objectives of this project are firstly to study the nm23 expression pattern in Pca and to study the relation between nm23 expression and CIN. Immunohistochemistry with a polyclonal antibody was employed to study the expression of the nm23 protein in formalin-fixed, paraffin-embedded tissue specimens obtained from patients with Pca [n 28], collected from the department of Pathology at King Abdulaziz Hospital [Jeddah, Saudi Arabia]. CIN was studied by using dualcolor interphase fluorescence in situ hybridization [IFISH] performed on archived Pca. Expression of nm23 was noted in 24 out of 28 Pca [85%]. Five of the patients have evidence of metastasis and four of them showed strong nm23 expression. CIN was detected in 8 out of 18 cases with interpretable IFISH signals. Nm23 expression was seen in 7/8 of CIN positive and in 8/10 of the CIN negative cases. Nm23 positivity was seen in 6/8 cases of Gleason score 6,12/14 cases of score 7, 4/4 cases of score 8 and 2/2 cases of score 9. Normal and hyperplastic tissue show either negative or weak cytoplasmic staining. The results suggest that expression of nm23 in Pca is not correlated to tumor metastasis in contrast to carcinoma in other organs. While our data suggest that nm23 may help in the distinction of normal from malignant prostatic tissue, these results do not point to nm23 as a reliable prognostic marker in Pca. Nm23 is not correlated to the CIN in Pca