nm23 protein expression in fine-needle aspirates from breast carcinoma: inverse correlation with cytologic grading, lymph node status, and ploidy.
BACKGROUND
nm23 has been recognized as a potential suppressor gene of metastasis. Reduced nm23 expression in breast carcinoma has been found to correlate with axillary lymph node metastases, high grade tumors, and shorter survival.


METHODS
nm23 protein was detected immunocytochemically using an avidin-biotin complex technique. When a few cells showed negative or marked reduced cytoplasmic staining, expression was considered reduced. Cytologic grading was performed on routine fine-needle aspirates (FNAC). Ploidy was determined by in situ hybridization of chromosomes 6, 7, 12, and 17 on interphase cell nuclei from FNAC. When all four chromosomes revealed a disome pattern, the tumor was classified as diploid; mixed disome/aneusome carcinomas as well as those with aneusomy in all four chromosomes were considered aneuploid.


RESULTS
Approximately 83% of specimens had reduced expression of nm23 protein. Forty-four of 45 lymph node positive tumors as well as 27 of 29 aneuploid tumors, were found to have reduced nm23 expression. Likewise, 49 of 57 Grade 2 (G2) carcinomas (86%) and 20 of 22 Grade 3 (G3) carcinomas (91%) showed reduced nm23 expression. Twenty-nine of 39 Grade 1 (G1) carcinomas (74%) had reduced nm23 expression. None of the G1 or G2 tumors with full nm23 expression had axillary lymph node metastases.


CONCLUSIONS
nm23 protein showed a significant inverse correlation with lymph node status, cytologic grading, and ploidy. The nm23 protein antibody may have potential as a preoperative marker in identifying subgroups of patients who either may have a worse prognosis than expected (e.g., those with G1 carcinomas with reduced nm23 expression) or who may be able to avoid axillary lymph node dissection (e.g., those with G1 carcinoma with full nm23 protein expression). Cancer
Sauer
T
T
Department of Pathology, Ullevaal University Hospital, Oslo, Norway.
Furu
I
I
Beraki
K
K
Jebsen
P W
PW
Ormerod
E
E
Naess
O
O
D014408:Biomarkers, Tumor; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics*; D009701:Nucleoside-Diphosphate Kinase; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins