Nm23 Protein Expression in Ductal In Situ and Invasive Human Breast Carcinoma

Background: Mortality associated with human breast carcinoma is almost entirely due to subsequent metastatic disease, but the molecular basis of this metastasis is not understood. Elucidation of the genetic control of metastatic propensity of a tumor is important in determining prognosis and choice...

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Published in:JNCI : Journal of the National Cancer Institute 1993-05, Vol.85 (9), p.727-731
Main Authors: Royds, Janice A., Stephenson, Timothy J., Rees, Robert C., Shorthouse, Andrew J., Silcocks, Paul B.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Breast cancer
Breast Diseases - metabolism
Breast Diseases - pathology
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Carcinoma in Situ - metabolism
Carcinoma, Intraductal, Noninfiltrating - metabolism
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical research
Medical sciences
Monomeric GTP-Binding Proteins
Neoplasm Proteins - metabolism
NM23 Nucleoside Diphosphate Kinases
Nucleoside-Diphosphate Kinase
Prognosis
Proteins
Proteins - metabolism
Regression Analysis
Transcription Factors
Tumors
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Summary:Background: Mortality associated with human breast carcinoma is almost entirely due to subsequent metastatic disease, but the molecular basis of this metastasis is not understood. Elucidation of the genetic control of metastatic propensity of a tumor is important in determining prognosis and choice of therapy. Expression of nm23, a putative metastasis suppressor gene, has been detected in human breast cancers, but studies have not consistently shown high levels of the Nm23 messenger RNA or protein to be associated with better histological differentiation. This inconsistency suggests that Nm23 protein may act independently as a metastasis suppressor. Purpose: The purpose of this retrospective study was to investigate the relationship of Nm23 protein expression with 1) histology in ductal breast carcinoma in situ and 2) the variables considered to be the major prognostic indicators in invasive breast carcinoma. Methods: We obtained formalin-fixed biopsy specimens of breast tissue excised from128 patients with breast lesions detected by mammography. Of these patients, 35 had been diagnosed with benign breast disease, 26 with ductal carcinoma in situ (DCIS), and 67 with invasive carcinoma. Tissue sections were embedded in paraffin blocks, and immunohistochemical staining was used to determine Nm23 expression. Specimens were rated positive if all lesional epithelium was stained and negative if any lesional epithelium was unstained. Statistical analysis was performed by multiple regression analysis because of non-orthogonality of the data. Results: All 35 examples of benign breast disease showed uniform epithelial cell staining. The seven cases of comedo DCIS were negative for Nm23 protein; all 18 noncomedo types were positive. Nm23 negativity was significantly associated with worsening invasive ductal carcinoma grade and advancing lymph node stage but not with tumor diameter or vascular invasion. Despite the putative antimetastatic role of the nm23 gene, no statistically significant association was found between Nm23 protein expression and vascular invasion. Conclusions: The precise role of the nm23 gene remains to be established, but our simplified immunohistochemical rating system shows an association between Nm23 protein expression and the two most significant prognostic factors relating to histologic grade and stage. Nm23 negativity distinguished comedo ductal carcinoma in situ from the other histological types, a finding consistent with the fact that comed
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/85.9.727