Detection of mammaglobin mRNA in peripheral blood is associated with high grade breast cancer: interim results of a prospective cohort study

BMC Cancer. 2008 Feb 20:8:55. doi: 10.1186/1471-2407-8-55.

Abstract

Background: We sought to examine the detection rate of cancer cells in peripheral blood (PBL) and in bone marrow (BM) using an established 7-gene marker panel and evaluated whether there were any definable associations of any individual gene with traditional predictors of prognosis.

Methods: Patients with T1-T3 primary breast cancer were enrolled into a prospective, multi-institutional cohort study. In this interim analysis 215 PBL and 177 BM samples were analyzed by multimarker, real-time RT-PCR analysis designed to detect circulating and disseminated breast cancer cells.

Results: At a threshold of three standard deviations from the mean expression level of normal controls, 63% (136/215) of PBL and 11% (19/177) of BM samples were positive for at least one cancer-associated marker. Marker positivity in PBL demonstrated a statistically significant association with grade II-III (vs. grade I; p = 0.0083). Overexpression of the mammaglobin (mam) gene alone had a statistically significant association with high tumor grade (p = 0.0315), and showed a trend towards ER-negative tumors and a high risk category. There was no association between marker positivity in PBL and the pathologic (H&E) and/or molecular (RT-PCR) status of the axillary lymph nodes (ALN).

Conclusion: This study suggests that molecular detection of circulating cancer cells in PBL detected by RT-PCR is associated with high tumor grade and specifically that overexpression of the mam gene in PBL may be a poor prognostic indicator. There was no statistically significant association between overexpression of cancer-associated genes in PBL and ALN status, supporting the concept of two potentially separate metastatic pathways.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow Cells / metabolism
  • Breast Neoplasms / blood*
  • Breast Neoplasms / genetics*
  • Cohort Studies
  • Female
  • Humans
  • Lymph Nodes / pathology
  • Mammaglobin A
  • Middle Aged
  • Neoplasm Proteins / blood*
  • Neoplasm Proteins / genetics*
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • RNA, Messenger / metabolism*
  • Uteroglobin / blood*
  • Uteroglobin / genetics*

Substances

  • Mammaglobin A
  • Neoplasm Proteins
  • RNA, Messenger
  • SCGB2A2 protein, human
  • Uteroglobin